Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-27T17:56:44.949Z Has data issue: false hasContentIssue false

The mechanisms that control the preantral to early antral follicle transition and the strategies to have efficient culture systems to promote their growth in vitro

Published online by Cambridge University Press:  24 May 2023

D. R. Nascimento
Affiliation:
Laboratory of Biotechnology and Physiology of Reproduction (LABIREP), Federal University of Ceará, Av. Comandante Maurocélio Rocha Ponte 100, CEP 62041-040, Sobral, CE, Brazil
E. C. Barbalho
Affiliation:
Laboratory of Biotechnology and Physiology of Reproduction (LABIREP), Federal University of Ceará, Av. Comandante Maurocélio Rocha Ponte 100, CEP 62041-040, Sobral, CE, Brazil
L. Gondim Barrozo
Affiliation:
Laboratory of Biotechnology and Physiology of Reproduction (LABIREP), Federal University of Ceará, Av. Comandante Maurocélio Rocha Ponte 100, CEP 62041-040, Sobral, CE, Brazil
E. I. T. de Assis
Affiliation:
Laboratory of Biotechnology and Physiology of Reproduction (LABIREP), Federal University of Ceará, Av. Comandante Maurocélio Rocha Ponte 100, CEP 62041-040, Sobral, CE, Brazil
F. C. Costa
Affiliation:
Laboratory of Biotechnology and Physiology of Reproduction (LABIREP), Federal University of Ceará, Av. Comandante Maurocélio Rocha Ponte 100, CEP 62041-040, Sobral, CE, Brazil
J. R. V. Silva*
Affiliation:
Laboratory of Biotechnology and Physiology of Reproduction (LABIREP), Federal University of Ceará, Av. Comandante Maurocélio Rocha Ponte 100, CEP 62041-040, Sobral, CE, Brazil
*
Corresponding author: J. R. V. Silva. Laboratory of Biotechnology and Physiology of Reproduction, Federal University of Ceará, Sobral, Ceará, Brazil, Av. Comandante Maurocélio Rocha Pontes, 100 – Derby, Sobral – CE, 62042-280, Brazil. Tel: +88 3611 8000. Email: [email protected]
Rights & Permissions [Opens in a new window]

Summary

Preantral to early antral follicles transition is a complex process regulated by endocrine and paracrine factors, as well as by a precise interaction among oocyte, granulosa cells and theca cells. Understanding the mechanisms that regulate this step of folliculogenesis is important to improve in vitro culture systems, and opens new perspectives to use oocytes from preantral follicles for assisted reproductive technologies. Therefore, this review aims to discuss the endocrine and paracrine mechanisms that control granulosa cell proliferation and differentiation, formation of the antral cavity, estradiol production, atresia, and follicular fluid production during the transition from preantral to early antral follicles. The strategies that promote in vitro growth of preantral follicles are also discussed.

Type
Review Article
Copyright
© Federal University of Ceará, 2023. Published by Cambridge University Press

Introduction

The transition from preantral (multilaminar follicles) to early antral follicles requires the action of local factors, hormones, and efficient bidirectional communication between granulosa cells and oocytes. Several attempts to promote in vitro growth of preantral follicles up to maturation have been reported in various domestic species (bovine: Paulino et al., Reference Paulino, Cunha, Barbalho Silva, Souza, Lopes, Donato, Peixoto, Matos-Brito, van den Hurk and Silva2018; Antonino et al., Reference Antonino, Soares, Júnior, de Alvarenga, Mohallem, Rocha, Vieira, de Souza, Beletti, Alves, Jacomini, Goulart and Alves2019; Bezerra et al., Reference Bezerra, Lima, Paulino, Silva, Silva, Souza, van den Hurk and Silva2019a; Paulino et al., Reference Paulino, Barroso, Silva, Souza, Bezerra, Silva, Donato, Peixoto and Silva2020; Vasconcelos et al., Reference Vasconcelos, Costa, Azevedo, Barroso, de Assis, Paulino, Silva, Silva, Souza and Silva2021; caprine: Ferreira et al., Reference Ferreira, Cadenas, Sá, Correia, Guerreiro, Lobo, Alves, Maside, Gastal, Rodrigues and Figueiredo2018; Soares-Costa et al., Reference Soares-Costa, Costa, Silva, Cunha, Paulino, Silva, Silva, van den Hurk and Silva2018; Pontes et al., Reference Pontes, Gouveia, Menezes, de Barros, Barberino, do Monte, Donfack, Celestino, Salgueiro, de Figueiredo and de Matos2019; ovine: Macedo et al., Reference Macedo, Santos, Bezerra, Menezes, Gouveia, Barbosa, Lins, Monte, Barberino, Batista, Barros, Wischral, Queiroz, Araújo and Matos2019; Mbemya et al., Reference Mbemya, de Sá, Guerreiro, de Sousa, Nguedia, Alves, Santos, Pessoa, Comizzoli, Figueiredo and Rodrigues2019; Barros et al., Reference Barros, Monte, Santos, Lins, Cavalcante, Gouveia, Müller, Oliveira, Donfack, Araújo and Matos2020; Silva et al., Reference Silva, Araújo, Silva, Gouveia, Barberino, Lins, Monte, Macedo, Santos, Menezes, Silva and Matos2021; Gomes et al., Reference Gomes, de Brito, de Sá, Ñaupas, Palomino, da Silva, Lopes, Mbemya, Alves, Zelinski, de Figueiredo and Rodrigues2022; and swine: de Lima et al., Reference de Lima, Rubessa, Rocha, Winters, Milner, Campello, Figueiredo and Wheeler2017; Kere et al., Reference Kere, Liu, Chen, Chao, Tsai, Yeh, Siriboon, Intawicha, Lo, Chiang, Fan and Ju2020). Different from mice (Eppig and O’Brien, Reference Eppig and O’Brien1996; O’Brien et al., Reference O’Brien, Pendola and Eppig2003), embryo production from in vitro cultured preantral follicles from human and domestic animals has not yet, however, been reported in the literature (Wu and Tian, Reference Wu and Tian2007; Arunakumari et al., Reference Arunakumari, Shanmugasundaram and Rao2010; de Figueiredo et al., Reference de Figueiredo, de Lima, Silva and Santos2018, Reference de Figueiredo, Cadenas, de Lima and Santos2020; Paulino et al., Reference Paulino, de Assis, Azevedo, Silva, da Cunha and Silva2022). The maintenance of bidirectional communication between the oocyte and the granulosa cells in cultured follicles, as well as the large quantity of messenger RNA (mRNA) and proteins that the oocyte needs to synthesize during its growth make it difficult the complete their development in vitro (Alam and Miyano, Reference Alam and Miyano2020; de Figueiredo et al., Reference de Figueiredo, Cadenas, de Lima and Santos2020; Paulino et al., Reference Paulino, de Assis, Azevedo, Silva, da Cunha and Silva2022).

The endocrine and paracrine control that regulates the transition from preantral to antral follicles is complex and involves a precise interaction of several factors (Araújo et al., Reference Araújo, Gastal, Figueiredo and Gastal2014; de Figueiredo et al., Reference de Figueiredo, de Lima, Silva and Santos2018, Reference de Figueiredo, Cadenas, de Lima and Santos2020). Any interference with this control can lead to ovarian disorders such as polycystic ovary syndrome (Abdel Aziz et al., Reference Abdel Aziz, Abdel-Wahab, Ibrahim and Kasimanickam2021; Asghari et al., Reference Asghari, Shokri-Asl, Rezaei, Tavallaie, Khafaei, Abdolmaleki and Majdi Seghinsara2021). The present review highlights the mechanisms involved in endocrine and paracrine control during the transition from preantral to early antral follicles, as well as the importance of granulosa cell proliferation, antral cavity formation, and estradiol production. The strategies to promote in vitro growth of preantral follicles are also discussed.

Endocrine and paracrine control during the transition from preantral to early antral follicles

The transition from preantral to early antral follicles is a step in which follicle development is regulated by intraovarian factors, but the follicles are responsive to gonadotropins. The slow growth of preantral and early antral follicles is gonadotropin independent, but progression to a late antral follicular state requires follicle-stimulating hormone (FSH; Iber and Geyter, Reference Iber and Geyter2013). FSH is the main endocrine regulator of follicle development (Paulino et al., Reference Paulino, Cunha, Barbalho Silva, Souza, Lopes, Donato, Peixoto, Matos-Brito, van den Hurk and Silva2018, Reference Paulino, Barroso, Silva, Souza, Bezerra, Silva, Donato, Peixoto and Silva2020; Vasconcelos et al., Reference Vasconcelos, Costa, Azevedo, Barroso, de Assis, Paulino, Silva, Silva, Souza and Silva2021) and its receptors are detectable in granulosa cells of preantral follicles in various species (murine: Camp et al., Reference Camp, Rahal and Mayo1991; human: Oktay et al., Reference Oktay, Briggs and Gosden1997; Méduri et al., Reference Méduri, Charnaux, Driancourt, Combettes, Granet, Vannier, Loosfelt and Milgrom2002; porcine: Durlej et al., Reference Durlej, Knapczyk-Stwora, Duda, Galas and Slomczynska2011; bubaline: Sharma et al., Reference Sharma, Dubey and Kumar2011; caprine: Saraiva et al., Reference Saraiva, Celestino, Araújo, Chaves, Almeida, Lima-Verde, Duarte, Silva, Martins, Bruno, Matos, Campello, Silva and Figueiredo2011; Barros et al., Reference Barros, Cavalcante, Macedo, Barberino, Lins, Gouveia, Menezes, Queiroz, Araújo, Palheta, Leite and Matos2013; Ferreira et al., Reference Ferreira, Cadenas, Sá, Correia, Guerreiro, Lobo, Alves, Maside, Gastal, Rodrigues and Figueiredo2018). This hormone stimulates granulosa cell proliferation and promotes follicular growth and antrum formation (Ferreira et al., Reference Ferreira, Cadenas, Sá, Correia, Guerreiro, Lobo, Alves, Maside, Gastal, Rodrigues and Figueiredo2018; de Figueiredo et al., Reference de Figueiredo, Cadenas, de Lima and Santos2020; Fushii et al., Reference Fushii, Yamada and Miyano2021). Other endocrine factors, such as melatonin have a functional role in preantral follicles by influencing their development, increasing the production of active mitochondria in oocytes and steroidogenesis in granulosa cells (Barros et al., Reference Barros, Cavalcante, Macedo, Barberino, Lins, Gouveia, Menezes, Queiroz, Araújo, Palheta, Leite and Matos2013; Riaz et al., Reference Riaz, Yousuf, Liang, Hua and Yang2019; Barros et al., Reference Barros, Monte, Santos, Lins, Cavalcante, Gouveia, Müller, Oliveira, Donfack, Araújo and Matos2020). It is well established that FSH stimulates the production of aromatase (Cyp19a1), which synthesizes 17β-estradiol, an important hormone for granulosa cell proliferation (Fitzpatrick and Richards, Reference Fitzpatrick and Richards1994; Bishonga et al., Reference Bishonga, Takahashi, Katagiri, Nagano and Ishikawa2001). Anti-Müllerian hormone (AMH) is also produced by granulosa cells of preantral and antral follicles (Umer et al., Reference Umer, Zhao, Sammad, Weldegebriall Sahlu, Yunwei and Zhu2019; Gautam et al., Reference Gautam, Vats, Pal, Haldar and De2021). It is already well established that this hormone prevents early depletion of follicles, but there is still much to elucidate in the role of this hormone during folliculogenesis. Rocha et al. (Reference Rocha, Rubessa, de Lima, da Silva, Winters, Polkoff, Milner, Campello, de Figueiredo and Wheeler2021) have shown that there is an interaction between AMH and FSH, in which AMH reduces FSH-induced estradiol and progesterone production. Tanimoto et al. (Reference Tanimoto, Sekii, Morohaku, Li, Pépin and Obata2021) showed that, for the development of a viable follicle, blockage of AMH production by oestrogen is needed.

Oocyte-derived factors, such as growth differentiation factor-9 (GDF-9), bone morphogenetic protein 15 (BMP-15), and fibroblast growth factor-2 (FGF-2) are important regulators of preantral follicle growth by inducing granulosa cell proliferation and differentiation, and antral cavity formation (Reineri et al., Reference Reineri, Coria, Barrionuevo, Hernández, Callejas and Palma2018; Monte et al., Reference Monte, Santos, Menezes, Gouveia, Lins, Barberino, Oliveira, Donfack and Matos2019). Other factors, such as epidermal growth factor (EGF) and insulin-like growth factor 1 (IGF-1), influence the development of preantral follicles by expanding oocyte diameter and inducing granulosa cell proliferation (Bezerra et al., Reference Bezerra, Monte, Barberino, Lins, Oliveira Junior, Santos, Bezerra, Neves, Silva, Carvalho and Matos2019b; Paulino et al., Reference Paulino, Barroso, Silva, Souza, Bezerra, Silva, Donato, Peixoto and Silva2020). Vascular endothelial growth factor (VEGF) is an important angiogenic factor that induces granulosa cell proliferation, an essential characteristic for the transition from preantral to antral follicles, and improves oocyte maturation (Araújo et al., Reference Araújo, Silva, Duarte, Magalhães, Almeida, Gonçalves, Bruno, Silva, Campello, Rodrigues and Figueiredo2011; da Silva et al., Reference da Silva, Rossetto, Chaves, Duarte, Araújo, Feltrin, Bernuci, Anselmo-Franci, Xu, Woodruff, Campello and Figueiredo2015; Cadenas et al., Reference Cadenas, Leiva-Revilla, Vieira, Apolloni, Aguiar, Alves, Lobo, Rodrigues, Apgar, Smitz, Figueiredo and Maside2017). Activin is another intraovarian factor that accelerates the growth of preantral follicles, estradiol synthesis, and mRNA expression for FSH receptor in rat granulosa cells (Tanaka et al., Reference Tanaka, Matsuzaki, Tanaka, Iwasa, Kuwahara and Irahara2019). Conversely, in bovine species, activin decreases the FSH stimulating action in the bovine preantral follicle cultured in vitro, which was associated with decreased levels of transcripts for hyaluronan synthases (HAS-1, HAS-2) and proliferating cell nuclear antigen (PCNA; Silva et al., Reference Silva, Bezerra, Costa, Rossi, Passos, Vasconcelos, Rossetto, Donato, Magalhães-Padilha, Campello, Saraiva, Figueiredo, Peixoto, Van den Hurk and Silva2014).

Granulosa cell proliferation and oocyte–granulosa cell interaction during the transition from preantral to early antral follicles

Granulosa cells form a favourable metabolic and hormonal environment for oocyte growth and maturation (Baumgarten and Stocco, Reference Baumgarten, Stocco and Skinner2018). Similarly, the oocyte can influence the proliferation of granulosa cells, providing follicular development through the production of growth factors such as BMP-15 and GDF-9 (de Figueiredo and de Lima, Reference de Figueiredo and de Lima2017; Baumgarten and Stocco, Reference Baumgarten, Stocco and Skinner2018). Orisaka et al. (Reference Orisaka, Orisaka, Jiang, Craig, Wang, Kotsuji and Tsang2006) showed that GDF-9 controls follicular fate by promoting its survival and growth during the preantral to early antral transition, suppressing granulosa cell apoptosis and follicular atresia through PI3K/Akt activation.

During the development of the preantral follicle, GDF-9 and BMP-15 continue to stimulate the proliferation of granulosa cells, however, they decrease the production of progesterone and increase the expansion and reorganization of granulosa cells to form the antrum cavity. In addition, GDF-9 stimulates the expression of FSH receptors in granulosa cells, which become responsive to gonadotropins and influence the differentiation and recruitment of theca cells, which form a scaffold structure, supporting the vascular system (De Conto et al., Reference De Conto, Matte and Cunha-Filho2021). Theca cells begin to produce luteinizing hormone (LH) receptors, steroidogenic enzymes and androgens (Young and McNeilly, Reference Young and McNeilly2010), while LH stimulates the production of androgens by theca cells, which are used by granulosa cells to produce 17β-estradiol (Xavier and Freitas, Reference Xavier and Freitas2021). 17β-Estradiol increases the sensitivity of granulosa cells to gonadotropins and IGF-1, which stimulates follicular steroidogenesis (Ginther et al., Reference Ginther, Beg, Bergfelt, Donadeu and Kot2001). BMP-4 and FSH also play an important regulatory role in the growth and steroidogenesis of preantral follicles. According to Sakaguchi et al. (Reference Sakaguchi, Huang, Yang, Yanagawa and Nagano2017), BMP-4 inhibits the luteinization of granulosa cells, while FSH increases their proliferation and the viability of the oocyte–cumulus–granulosa complex.

Granulosa cells produce several autocrine and paracrine factors that may be involved in the initiation of antrum formation such as kit ligand, activins, inhibins, hyaluronan, Versican, AMH and transforming growth factor α (TGFα). These factors also synchronize oocyte growth, granulosa cell proliferation and theca cell differentiation (Vasconcelos et al., Reference Vasconcelos, Saraiva, Costa, Passos, Silva, Rossi, Portela, Duarte, Magalhães-Padilha, Campelo, Figueiredo, Van den Hurk and Silva2013; Dumesic et al., Reference Dumesic, Meldrum, Katz-Jaffe, Krisher and Schoolcraft2015). In this sense, the interaction between the oocyte and granulosa cells, as well as the differentiation and proliferation of theca cells, can be determinants for the progress of preantral follicle growth, steroidogenesis and oocyte maturation (Chu et al., Reference Chu, Xu, Yang and Sun2018; Alam and Miyano, Reference Alam and Miyano2020). AMH plays an inhibitory role in modulating the responsiveness of granulosa and theca cells to gonadotrophic stimuli, thereby regulating follicular progression from the gonadotropin-responsive to the gonadotropin-dependent stage (Campbell et al., Reference Campbell, Clinton and Webb2012).

After antrum formation, granulosa cells are physically separated into mural granulosa cells, which organize along the follicle wall, and cumulus granulosa cells, which surround the oocyte (Baumgarten and Stocco, Reference Baumgarten, Stocco and Skinner2018; Zhang, Reference Zhang and Skinner2018). Cumulus granulosa cells nourish the oocyte by providing specific amino acids, glycolysis products and cholesterol biosynthesis substrates through gap junctions (Baumgarten and Stocco, Reference Baumgarten, Stocco and Skinner2018). In addition, they prevent premature oocyte maturation and resumption of meiosis in the oocyte by maintaining high levels of cAMP in the oocyte (Russell and Robker, Reference Russell, Robker and Skinner2018; Zhang, Reference Zhang and Skinner2018). The mechanisms that control the transition from preantral to early antral follicles are shown in Figure 1 and Table 1.

Figure 1. Factors that control the transition from preantral to early antral follicle.

Table 1. Role of growth factors in oocyte, granulosa and theca cells during the transition from preantral to early antral follicle

Mechanisms of antrum formation in preantral follicles

When the distance between the mural granulosa and the cumulus cells increases, the formation of the antral cavity occurs, marking the preantral to early antral follicles transition (Chu et al., Reference Chu, Xu, Yang and Sun2018). The antral cavity is formed between the granulosa cells and requires a fluid ingress from the vascularization of theca cells via membrane proteins such as aquaporins (AQPs; Kawashima and Kawamura, Reference Kawashima and Kawamura2018; Paz et al., Reference Paz, de Sousa, Alves, Lobo, Sales, Tavares, de Sá, Guerreiro, Maside, Rocha, Bertolini, Bordignon, de Figueiredo and Rodrigues2018). Several AQPs, such as AQP5, AQP7, AQP8, and AQP9, are related to the influx of water through the follicle wall to form follicular fluid. These membrane proteins are expressed in the granulosa cells of different species (swine: Skowronski et al., Reference Skowronski, Kwon and Nielsen2009; ovine: Sales et al., Reference Sales, Duarte, Rodrigues, Lima, Silva, Carvalho, Brito, da Maranguape, Lobo, Aragão, Moura, Figueiredo and Rodrigues2015; bovine: Ishibashi et al., Reference Ishibashi, Hara and Kondo2009). Paz et al. (Reference Paz, de Sousa, Alves, Lobo, Sales, Tavares, de Sá, Guerreiro, Maside, Rocha, Bertolini, Bordignon, de Figueiredo and Rodrigues2018) also demonstrated the presence of AQP3 in granulosa cells, and is also involved in the expansion of the antral cavity during the transition from preantral to the antral follicle. Antrum formation depends on the stimulation of local factors for the production and secretion of polysaccharides and proteins by the granulosa cells, which accumulate and generate an osmotic gradient that attracts fluid from the thecal vasculature (Baumgarten and Stocco, Reference Baumgarten, Stocco and Skinner2018). It is recognized that granulosa cells express the enzymes that synthesize hyaluronic acid, Versican and perlecan, which are responsible for the formation of follicular fluid (Schoenfelder and Einspanier, Reference Schoenfelder and Einspanier2003; Clarke et al., Reference Clarke, Hope, Byers and Rodgers2006; Vasconcelos et al., Reference Vasconcelos, Saraiva, Costa, Passos, Silva, Rossi, Portela, Duarte, Magalhães-Padilha, Campelo, Figueiredo, Van den Hurk and Silva2013; Nagyova et al., Reference Nagyova, Salustri, Nemcova, Scsukova, Kalous and Camaioni2020).

The development of the antral cavity is intensified by granulosa cell activity. Alam et al. (Reference Alam, Lee and Miyano2018) showed that, even without the presence of an oocyte, GDF-9 and BMP-15 influence the production of antrum-like structures. GDF-9 is known to stimulate Versican and perlecan expression and interacts favourably with FSH to increase hyaluronan synthetase 2 expression (Vasconcelos et al., Reference Vasconcelos, Saraiva, Costa, Passos, Silva, Rossi, Portela, Duarte, Magalhães-Padilha, Campelo, Figueiredo, Van den Hurk and Silva2013; Silva et al., Reference Silva, Bezerra, Costa, Rossi, Passos, Vasconcelos, Rossetto, Donato, Magalhães-Padilha, Campello, Saraiva, Figueiredo, Peixoto, Van den Hurk and Silva2014). Hyaluronan, proteoglycans and their glycosaminoglycan side chains are osmotic solutes that act to increase the osmotic pressure inside the follicle, resulting in fluid accumulation (Rodgers and Irving-Rodgers, Reference Rodgers and Irving-Rodgers2010). Some studies have also demonstrated that EGF increases mRNA levels for GDF-9 in in vitro cultured preantral follicles (Alam et al., Reference Alam, Lee and Miyano2018; Paulino et al., Reference Paulino, Barroso, Silva, Souza, Bezerra, Silva, Donato, Peixoto and Silva2020), showing that EGF acts via GDF-9 to promote antral cavity formation. The mechanisms involved in the formation of antral cavity formation are shown in Figure 2.

Figure 2. Hormones and growth factors that control the formation of the antral cavity during the transition from preantral to early antral follicles.

Production of estradiol during the transition from preantral to early antral follicles

When preantral follicles reach six or seven layers of granulosa cells, the inner layer of theca becomes active and the formation of the antral cavity begins. Increased 17β-estradiol in follicular fluid is associated with increased mRNA expression for CYP19A1 in granulosa cells (García-Guerra et al., Reference García-Guerra, Canavessi, Monteiro, Mezera, Sartori, Kirkpatrick and Wiltbank2018).

As a growing follicle acquires sufficient aromatase activity as a result of FSH stimulation, estradiol production suppresses FSH secretion below that necessary to support the development of less mature follicles, which consequently suffer atresia (Zeleznik, Reference Zeleznik2004). Therefore, estradiol biosynthesis is a tightly regulated molecular process, dependent on the expression of key steroidogenic enzymes by FSH and intraovarian signalling molecules, including beta-catenin, an essential co-transcription factor for maximal induction of the aromatase mRNA transcript and subsequent estradiol production (Forrest et al., Reference Forrest, Flores, Gurule, Soto-Navarro, Shuster, Gifford and Gifford2022). β-Catenin regulates the transformation of androgen to estradiol by increasing the transcription of CYP19A1 through functional interactions with steroidogenic factor-1 (SF1; Forrest et al., Reference Forrest, Flores, Gurule, Soto-Navarro, Shuster, Gifford and Gifford2022). Furthermore, LH promotes preantral to antral follicular transition by upregulating follicular androgen biosynthesis (Orisaka et al., Reference Orisaka, Hattori, Fukuda, Mizutani, Miyamoto, Sato, Tsang, Kotsuji and Yoshida2013).

Expression of luteinizing hormone/choriogonadotropin receptor (LHCGR) and cytochrome P450 family 17, subfamily A, member 1 (CYP17A1) mRNAs appear in large preantral follicles, concomitantly with theca differentiation. Followed by the expression of steroidogenic acute regulatory protein (StAR) in 1.0 mm antral follicles, granulosa cells from preantral and early antral follicles do not express StAR. Therefore, steroidogenesis in bovine follicles potentially begins in follicles ≥ 1.0 mm. Furthermore, the mRNA for CYP17A1 was located exclusively in theca internal cells, which indicates that the conversion of progestogens to androgens occurs only in the theca interna (Braw-Tal and Roth, Reference Braw-Tal and Roth2005). Furthermore, the neonatal rat ovary is completely devoid of antral follicles at birth. By day 12 of age, small-sized to medium-sized antral follicles are present, in addition to follicles at all preceding stages of development. During the intervening period the ovary becomes steroidogenically active, and responsive to gonadotrophins on days 7–9 of age, suggesting that granulosa and theca cells become active at that time (Carson and Smith, Reference Carson and Smith1986).

The expression of key enzymes involved in steroidogenesis is crucial for the proper development of the follicles. It has been observed that the mRNA encoding P450arom was not detectable until early antral cavity formation, in addition to being expressed only in granulosa cells (Yuan et al., Reference Yuan, Wang, Lan, Sui, Yu and Tan2008). The mechanisms involved in the production of estradiol during the transition from preantral to early antral follicles are shown in Figure 2.

Follicle atresia during the transition from preantral to early antral follicles

Follicular atresia is characterized by morphological changes in the oocyte, granulosa, and theca cells that culminate with follicular death and, consequently, regulate the capacity of females to generate mature gametes during the fertile period (Makarevich et al., Reference Makarevich, Földešiová, Pivko, Kubovičová and Chrenek2018). This process promotes a drastic reduction in the ovarian follicle population during the reproductive lifespan. According to Zhang et al. (Reference Zhang, Liu, Yao, Li, Liu and Pan2018), crosstalk among cell apoptosis, autophagy and ferroptosis is involved in the control of atresia in ovarian follicles. In preantral follicles, degeneration initially occurs in the oocyte and, subsequently, in granulosa cells (Meng et al., Reference Meng, Jan, Hamer, van Pelt, van der Stelt, Keijer and Teerds2018). The first signs of atresia in the oocyte are the retraction of nuclear chromatin and oocyte fragmentation, which triggers the process of irreversible elimination of ovarian follicles at this stage of development. In the granulosa cells of preantral follicles, changes are rarely observed.

Zoheir et al. (Reference Zoheir, Darwish, Liguo and Ashour2021) showed that cellular DNA fragmentation is an important biochemical marker of apoptosis during follicular atresia. Other evidence confirmed that apoptosis is not the only death pathway active in the ovary. Gannon et al. (Reference Gannon, Stämpfli and Foster2012) reported a decrease in preantral follicle numbers without a concomitant increase in apoptosis, and no change in apoptosis markers caspase 3 and TUNEL. Recent studies have demonstrated that, in granulosa cells from cultured preantral follicles of buffaloes, transmembrane protein AQP8 is involved in the regulation of cycle progression and apoptosis (Cao et al., Reference Cao, Li, Huang, Shi and Li2021). Furthermore, miRNAs have been shown to control several fundamental biological processes, including follicular atresia through their target genes and signalling pathways, and play a central role in the regulation of autophagy (Ma et al., Reference Ma, Tang, Guo, Liang, Zhang and Jiang2020). Gannon et al. (Reference Gannon, Stämpfli and Foster2012) showed that degeneration of preantral follicles is associated with the activation of the autophagy cascade. Meng et al. (Reference Meng, Jan, Hamer, van Pelt, van der Stelt, Keijer and Teerds2018) reported that the standard pathway of degeneration in preantral follicles is through autophagy, and that the activation of this pathway occurs under normal physiological conditions. Considering that, in vivo, follicular atresia during preantral to early antral follicles transition is controlled by various intrafollicular regulators such as growth factors, cytokines, and steroids (Orisaka et al., Reference Orisaka, Jiang, Orisaka, Kotsuji and Tsang2009a), the development of strategies to interrupt atresia is a difficult task.

Despite early antral follicles (∼2.0 mm in diameter – human species) are still not dependent on gonadotropins, Orisaka et al. (Reference Orisaka, Tajima, Tsang and Kotsuji2009b) showed that they are susceptible to apoptotic signals. In these follicles, with the progression of atresia, there is a reduction in the number of layers of granulosa cells, and invasion of fibroblasts and macrophages (Seneda et al., Reference Seneda, Bergamo, González, Zangirolamo and Morotti2021). Meng et al. (Reference Meng, Jan, Hamer, van Pelt, van der Stelt, Keijer and Teerds2018) reported that atresia in these follicles was associated with the activation of the autophagy cascade. Increasing the levels of microtubule-associated light chain protein 3 (LC3) and of autophagy homeostasis-associated protein BECLIN1 is linked with the death of preantral and early antral follicles by the autophagy cascade (Gordy and He, Reference Gordy and He2012). Activation of this pathway occurs under normal physiological conditions and the presence of LC3, sequestosome 1 (SQSTM1/P62) and autophagy-related protein 7 (ATG7) are markers for autophagy (Gannon et al., Reference Gannon, Stämpfli and Foster2012). During atresia of those follicles, Meng et al. (Reference Meng, Jan, Hamer, van Pelt, van der Stelt, Keijer and Teerds2018) also reported that a loss in mitochondrial antioxidant capacity in granulosa cells led to the activation of AMP-activated protein kinase alpha 1 (AMPK-α1) and AMPK-α2, while at the same time the expression of protein kinase B (AKT) and mammalian target survival of the rapamycin complex 1 (mTORC1) was decreased. AMPK is an important regulator of metabolism, an inhibitor of the mTORC1 complex, and a direct activator of autophagy (Emerling et al., Reference Emerling, Weinberg, Snyder, Burgess, Mutlu, Viollet, Budinger and Chandel2009; Egan et al., Reference Egan, Shackelford, Mihaylova, Gelino, Kohnz, Mair, Vasquez, Joshi, Gwinn, Taylor, Asara, Fitzpatrick, Dillin, Viollet, Kundu, Hansen and Shaw2011; Kim et al., Reference Kim, Kundu, Viollet and Guan2011). Oxidative stress is able to reduce superoxide dismutase (SOD) expression in granulosa cells of preantral follicles, and to activate AMPK, which leads to the activation of autophagy. The mechanisms that regulate the preantral and early antral follicles atresia are shown in Figure 3.

Figure 3. Mechanisms that control production of estradiol (E2) during the transition from preantral to early antral follicles.

Strategies to promote in vitro growth of preantral follicles

Preantral follicles represent 90% of the ovarian follicle population and, therefore, the development of effective culture systems to promote their growth in vitro is an interesting field of study in regard to avoiding the process of atresia that naturally occurs in vivo during the late antral stages of development. Follicular growth, antrum formation and acquisition of oocyte competence have been obtained in some species through the addition of different substances such as hormones, growth factors and cytokines to the culture medium in species that require short culture periods, such as murine (O’Brien et al., Reference O’Brien, Pendola and Eppig2003). However, in human and large animal species, the development of primordial to preovulatory follicles is a very long process (∼6 months; Paulino et al., Reference Paulino, de Assis, Azevedo, Silva, da Cunha and Silva2022) and various researchers have been working to develop efficient culture systems.

The limitations of in vitro culture of preantral follicles come from the difficulty of maintaining the three-dimensional structure of follicles, and the many signals necessary to coordinate the stimulation of follicular growth (Paulino et al., Reference Paulino, de Assis, Azevedo, Silva, da Cunha and Silva2022). Although bi-dimensional (2D) follicle culture has been successfully performed in many studies (da Cunha et al., Reference da Cunha, Melo, Sousa, Araújo, Vasconcelos, Silva and Silva2018; Paulino et al., Reference Paulino, Cunha, Barbalho Silva, Souza, Lopes, Donato, Peixoto, Matos-Brito, van den Hurk and Silva2018, Reference Paulino, Barroso, Silva, Souza, Bezerra, Silva, Donato, Peixoto and Silva2020; Vasconcelos et al., Reference Vasconcelos, Costa, Azevedo, Barroso, de Assis, Paulino, Silva, Silva, Souza and Silva2021), a major limitation of these systems is their inability to maintain follicle architecture, with the oocyte surrounded by granulosa cells. This is particularly problematic with follicles from large mammalian species that require longer term cultures (Simon et al., Reference Simon, Kumar and Duncan2020). Given the importance of maintaining the follicle complex architecture, three-dimensional (3D) culture systems can help to maintain follicle complex architecture (Simon et al., Reference Simon, Kumar and Duncan2020). For this system, various types of matrices are used to encapsulate follicles to maintain follicle architecture and cell–cell interactions, thereby creating a microenvironment similar to that of the in vivo ovary, improving somatic cell proliferation and oocyte growth (Belli et al., Reference Belli, Vigone, Merico, Redi, Zuccotti and Garagna2012). In general, matrices have been engineered from natural components such as collagen and alginate (Healy et al., Reference Healy, Dolitsky, Villancio-Wolter, Raghavan, Tillman, Morgan, DeCherney, Park and Wolff2021), or Matrigel (Hao et al., Reference Hao, Tuck, Prakash, Damdimopoulos, Sjödin, Lindberg, Niklasson, Pettersson, Hovatta and Damdimopoulou2020), or from synthetic components such as polyethylene glycol (Green and Shikanov, Reference Green and Shikanov2016; Tomaszewski et al., Reference Tomaszewski, DiLillo, Baker, Arnold and Shikanov2021). Maintaining the follicular shape along with regulating the physical and chemical features of the microenvironment can be used as a tool to understand the underlying biology of follicle growth and maturation (Ghorbani et al., Reference Ghorbani, Eyni, Norahan, Zarrintaj, Urban, Mohammadzadeh, Mostafavi and Sutherland2022; Khunmanee and Park, Reference Khunmanee and Park2022).

Preantral follicles cultured in the 3D system had greater homogeneity of daily growth, higher rates of viability and antrum formation, as well as low rates of degeneration (Antonino et al., Reference Antonino, Soares, Júnior, de Alvarenga, Mohallem, Rocha, Vieira, de Souza, Beletti, Alves, Jacomini, Goulart and Alves2019; Panta et al., Reference Panta, Silva, Padilha, Correia, Rondina, Figueiredo and Magalhães Padilha2019). Preantral follicles from other species have been successfully cultured in a three-dimensional culture system using alginate and fibrin (monkey: Xu et al., Reference Xu, Xu, Bernuci, Fisher, Shea, Woodruff, Zelinski and Stouffer2013; Bulgarelli et al., Reference Bulgarelli, Ting, Gordon, de Sá Rosa-e-Silva and Zelinski2018; cat: Chansaenroj et al., Reference Chansaenroj, Songsasen and Chatdarong2019; human: Chiti et al., Reference Chiti, Dolmans, Hobeika, Cernogoraz, Donnez and Amorim2017).

Multistep culture systems have also been developed to further mimic the physiologic environment of developing follicles (Green and Shikanov, Reference Green and Shikanov2016; Simon et al., Reference Simon, Kumar and Duncan2020). These systems have been used for culturing early preantral follicles. The multistep method starts with the culture of ovarian cortical tissue for 3 weeks to initiate primordial follicle activation and to support follicle growth to the preantral stage. At the end of ovarian tissue culture, preantral follicles are isolated mechanically and cultured individually or in a group for 6 weeks (Xu et al., Reference Xu, Lawson, Bean, Ting, Pejovic, De Geest, Moffitt, Mitalipov and Xu2021). In this system, Xu et al. (Reference Xu, Lawson, Bean, Ting, Pejovic, De Geest, Moffitt, Mitalipov and Xu2021) demonstrated that ∼50% of human follicles survived for 6 weeks. Most surviving follicles grew to the antral stage and produced the ovarian steroid hormones estradiol and progesterone, in addition to paracrine factors such as activin A, IGF-2 and VEGF. In addition, the cultured preantral follicles exhibited morphology similar to that of human follicles developed in vivo.

Many efforts have been made to elucidate the mechanisms involved in the growth of preantral follicles, as reviewed recently by Paulino et al. (Reference Paulino, de Assis, Azevedo, Silva, da Cunha and Silva2022). Although comprehension of the molecular regulation and composition of the microenvironment coordinating the events in preantral follicles remains incomplete, over time many studies have been conducted to optimize culture systems to support follicular growth (Healy et al., Reference Healy, Dolitsky, Villancio-Wolter, Raghavan, Tillman, Morgan, DeCherney, Park and Wolff2021). Preantral follicles from human and animal species require the development of a tightly regulated culture system with adequate nutrients, cytokines, growth factors, and developmental stage-dependent hormones to support cell survival and proliferation, as well as cellular function, which changes as follicles grow and oocytes mature (Simon et al., Reference Simon, Kumar and Duncan2020; Paulino et al., Reference Paulino, de Assis, Azevedo, Silva, da Cunha and Silva2022). Therefore, understanding the influence of several compounds for supplementation of culture medium for preantral follicles is fundamental. In this context, melatonin increases follicular and oocyte diameters, forms the antral cavity and preserves high rates of morphologically intact sheep preantral follicles for up to 18 days of culture (Barros et al., Reference Barros, Monte, Santos, Lins, Cavalcante, Gouveia, Müller, Oliveira, Donfack, Araújo and Matos2020).

Another alternative to improve follicular development in vitro is to supplement the culture medium with EGF, whose signalling regulates many cellular processes associated with survival (Sabbah et al., Reference Sabbah, Hajjo and Sweidan2020). EGF has an important role in folliculogenesis, by promoting several processes, such as granulosa and theca cell proliferation (Jachter et al., Reference Jachter, Simmons, Estill, Xu and Bishop2022). The effects of adding EGF to the culture medium are directly associated with improved survival of bovine preantral follicles. In general, EGF-treated follicles reach a larger diameter at the end of the culture period (Paulino et al., Reference Paulino, Barroso, Silva, Souza, Bezerra, Silva, Donato, Peixoto and Silva2020; Jachter et al., Reference Jachter, Simmons, Estill, Xu and Bishop2022). Hormones, such as progesterone, and cytokines, such as TNF-α, are able to maintain healthy follicle morphology and positively influence follicular growth and antrum formation in cattle (Paulino et al., Reference Paulino, Cunha, Barbalho Silva, Souza, Lopes, Donato, Peixoto, Matos-Brito, van den Hurk and Silva2018, Reference Paulino, Barroso, Silva, Souza, Bezerra, Silva, Donato, Peixoto and Silva2020). Also in cattle, preantral follicles cultured in the presence of BMP-2 or BMP-4 showed a significant increase in follicular diameter and greater average daily growth (da Cunha et al., Reference da Cunha, Melo, Sousa, Araújo, Vasconcelos, Silva and Silva2018).

Understanding the mRNA transcription of preantral follicles can provide important insights to detect follicular gene expression at several critical stages of its development under different culture conditions. Therefore, the identification of genes differentially expressed at each of growth and follicular stage development can be used to elucidate the processes involved in follicular growth (Paulini et al., Reference Paulini, Araujo, Silva and Lucci2022). In bovine species, an overexpression of mRNA for oocyte maturation factor Mos (c-MOS) and GDF-9 was observed when oocytes from preantral follicles were cultured in the presence of EGF. Furthermore, higher levels of cyclin B1 and GDF9 mRNA were observed in oocytes from follicles cultured with progesterone (Paulino et al., Reference Paulino, Barroso, Silva, Souza, Bezerra, Silva, Donato, Peixoto and Silva2020). In addition, bovine preantral follicles cultured in the presence of alpha-lipoic acid expressed higher levels of transcripts for the FSH receptor, LHCGR, IGF-1, BMPR1a, TGFβ1, TGFβR1, ActRIIB, GDF9, and activin. The expression of pro-apoptotic genes BCL2 associated X (BAX) and c-Myc were also downregulated (Zoheir et al., Reference Zoheir, Harisa, Allam, Yang, Li, Liang, Abd-Rabou and Harrath2017).

To mitigate the effects of oxidative stress induced by culture conditions, such as lower quality oocytes, follicular cell death, inactivation of antioxidant enzymes, and mitochondrial damage, there has been an increasing interest in the antioxidant potential of natural compounds (Lins et al., Reference Lins, Cavalcante, Santos, Menezes, Barros, Barberino, Bezerra, Macedo and Matos2017). Preantral follicles from sheep cultured in medium supplemented with kaempferol showed high percentages of follicular survival, antrum formation, and greater follicular diameter. In addition, kaempferol preserves higher levels of metabolically active mitochondria (Santos et al., Reference Santos, Monte, Lins, Barberino, Menezes, Gouveia, Macedo, Oliveira Júnior, Donfack and Matos2019). In cattle, the presence of eugenol in a culture medium promoted higher daily growth rates of bovine preantral follicles, in addition to stimulating the expression of mRNA for glutathione peroxidase 1 (GPX1; Vasconcelos et al., Reference Vasconcelos, Costa, Azevedo, Barroso, de Assis, Paulino, Silva, Silva, Souza and Silva2021). The strategies to promote in vitro growth of preantral follicles are represented in Figure 4.

Figure 4. Strategies to promote in vitro growth of preantral follicles.

Final considerations

The transition from preantral to antral requires intense and precise granulosa–oocyte interaction, any dysregulation can interfere with the acquisition of oocyte competence. Endocrine, paracrine and autocrine factors are essential for follicular growth, antral cavity formation, granulosa cell proliferation, differentiation, and future gonadotropin dependence. In vitro studies have contributed to a better understanding of the roles of hormones and growth factors during follicular development, addressing molecular events and bidirectional communications between the oocyte and surrounding granulosa cells.

Data availability

All data searched in this study are included in this publication.

Acknowledgements

The authors thank Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for scholarships. J. R. V. Silva is a researcher of Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq (grant number 308737/2018-0).

Conflict of interest

The authors declare that they have no competing interests.

References

Abdel Aziz, R. L., Abdel-Wahab, A., Ibrahim, M. A. and Kasimanickam, R. K. (2021). Transcript abundance of anti-Müllerian hormone and follicle-stimulating hormone receptor predicted superstimulatory response in embryo donor Holstein cows. Reproduction in Domestic Animals, 56(1), 153160. doi: 10.1111/rda.13859 CrossRefGoogle ScholarPubMed
Adashi, E. Y., Resnick, C. E., D’Ercole, A. J., Svoboda, M. E. and van Wyk, J. J. (1985). Insulin-like growth factors as intraovarian regulators of granulosa cell growth and function. Endocrine Reviews, 6(3), 400420. doi: 10.1210/edrv-6-3-400 CrossRefGoogle ScholarPubMed
Alam, M. H., Lee, J. and Miyano, T. (2018). GDF9 and BMP15 induce development of antrum-like structures by bovine granulosa cells without oocytes. Journal of Reproduction and Development, 64(5), 423431. doi: 10.1262/jrd.2018-078 CrossRefGoogle ScholarPubMed
Alam, M. H. and Miyano, T. (2020). Interaction between growing oocytes and granulosa cells in vitro . Reproductive Medicine and Biology, 19(1), 1323. doi: 10.1002/rmb2.12292 CrossRefGoogle ScholarPubMed
Ang, L., Xingping, G., Haixia, C., Zhulin, W. and Huaixiu, W. (2022). Assessment of cGMP level in medium during in vitro growth period of murine preantral follicles with and without supplementation of C-type natriuretic peptide. Zygote, 30(1), 98102. doi: 10.1017/S0967199421000393 CrossRefGoogle ScholarPubMed
Antonino, D. C., Soares, M. M., Júnior, J. M., de Alvarenga, P. B., Mohallem, R. F. F., Rocha, C. D., Vieira, L. A., de Souza, A. G., Beletti, M. E., Alves, B. G., Jacomini, J. O., Goulart, L. R. and Alves, K. A. (2019). Three-dimensional levitation culture improves in-vitro growth of secondary follicles in bovine model. Reproductive Biomedicine Online, 38(3), 300311. doi: 10.1016/j.rbmo.2018.11.013 CrossRefGoogle ScholarPubMed
Araújo, V. R., Lima-Verde, I. B., Name, K. P. O., Báo, S. N., Campello, C. C., Silva, J. R. V., Rodrigues, A. P. R. and Figueiredo, J. Rd. (2010). Bone morphogenetic protein-6 (BMP-6) induces atresia in goat primordial follicles cultured in vitro . Pesquisa Veterinária Brasileira, 30(9), 770781. doi: 10.1590/S0100-736X2010000900010 CrossRefGoogle Scholar
Araújo, V. R., Silva, G. M., Duarte, A. B., Magalhães, D. M., Almeida, A. P., Gonçalves, R. F., Bruno, J. B., Silva, T. F., Campello, C. C., Rodrigues, A. P. and Figueiredo, J. R. (2011). Vascular endothelial growth factor-A(165) (VEGF-A(165)) stimulates the in vitro development and oocyte competence of goat preantral follicles. Cell and Tissue Research, 346(2), 273281. doi: 10.1007/s00441-011-1251-1 CrossRefGoogle Scholar
Araújo, V. R., Gastal, M. O., Figueiredo, J. R. and Gastal, E. L. (2014). In vitro culture of bovine preantral follicles: A review. Reproductive Biology and Endocrinology: RB&E, 12, 78. doi: 10.1186/1477-7827-12-78 CrossRefGoogle ScholarPubMed
Arunakumari, G., Shanmugasundaram, N. and Rao, V. H. (2010). Development of morulae from the oocytes of cultured sheep preantral follicles. Theriogenology, 74(5), 884894. doi: 10.1016/j.theriogenology.2010.04.013 CrossRefGoogle ScholarPubMed
Asghari, R., Shokri-Asl, V., Rezaei, H., Tavallaie, M., Khafaei, M., Abdolmaleki, A. and Majdi Seghinsara, A. M. (2021). Alteration of TGFB1, GDF9, and BMPR2 gene expression in preantral follicles of an estradiol valerate-induced polycystic ovary mouse model can lead to anovulation, polycystic morphology, obesity, and absence of hyperandrogenism. Clinical and Experimental Reproductive Medicine, 48(3), 245254. doi: 10.5653/cerm.2020.04112 CrossRefGoogle ScholarPubMed
Assou, S., Al-Edani, T., Haouzi, D., Philippe, N., Lecellier, C. H., Piquemal, D., Commes, T., Aït-Ahmed, O., Dechaud, H. and Hamamah, S. (2013). MicroRNAs: New candidates for the regulation of the human cumulus–oocyte complex. Human Reproduction, 28(11), 30383049. doi: 10.1093/humrep/det321 CrossRefGoogle ScholarPubMed
Barros, V. R. P., Cavalcante, A. Y. P., Macedo, T. J. S., Barberino, R. S., Lins, T. L. B., Gouveia, B. B., Menezes, V. G., Queiroz, M. A. A., Araújo, V. R., Palheta, R. C. Jr, Leite, M. C. P. and Matos, M. H. T. (2013). Immunolocalization of melatonin and follicle-stimulating hormone receptors in caprine ovaries and their effects during in vitro development of isolated pre-antral follicles. Reproduction in Domestic Animals, 48(6), 10251033. doi: 10.1111/rda.12209 CrossRefGoogle ScholarPubMed
Barros, V. R. P., Monte, A. P. O., Santos, J. M. S., Lins, T. L. B. G., Cavalcante, A. Y. P., Gouveia, B. B., Müller, M. C., Oliveira, J. L., Donfack, N. J., Araújo, V. R. and Matos, M. H. T. (2020). Melatonin improves development, mitochondrial function and promotes the meiotic resumption of sheep oocytes from in vitro grown secondary follicles. Theriogenology, 144, 6773. doi: 10.1016/j.theriogenology.2019.12.006 CrossRefGoogle ScholarPubMed
Baumgarten, S. C. and Stocco, C. (2018). Granulosa cells. In: Skinner, M. K. (ed.) Encyclopedia of Reproduction 2nd edition, Academic Press, pp. 813. doi: 10.1016/B978-0-12-801238-3.64623-8 CrossRefGoogle Scholar
Belli, M., Vigone, G., Merico, V., Redi, C. A., Zuccotti, M. and Garagna, S. (2012). Towards a 3D culture of mouse ovarian follicles. International Journal of Developmental Biology, 56(10–12), 931937–9377. doi: 10.1387/ijdb.120175mz CrossRefGoogle ScholarPubMed
Bezerra, F. T. G., Lima, F. E. O., Paulino, L. R. F. M., Silva, B. R., Silva, A. W. B., Souza, A. L. P., van den Hurk, R. and Silva, J. R. V. (2019a). In vitro culture of secondary follicles and prematuration of cumulus–oocyte complexes from antral follicles increase the levels of maturation-related transcripts in bovine oocytes. Molecular Reproduction and Development, 86(12), 18741886. doi: 10.1002/mrd.23284 CrossRefGoogle ScholarPubMed
Bezerra, M. É. S., Monte, A. P. O., Barberino, R. S., Lins, T. L. B. G., Oliveira Junior, J. L. O., Santos, J. M. S., Bezerra, D. O., Neves, C. A., Silva, G. C., Carvalho, M. A. M. and Matos, M. H. T. (2019b). Conditioned medium of ovine Wharton’s jelly-derived mesenchymal stem cells improves growth and reduces ROS generation of isolated secondary follicles after short-term in vitro culture. Theriogenology, 125, 5663. doi: 10.1016/j.theriogenology.2018.10.012 CrossRefGoogle ScholarPubMed
Bishonga, C., Takahashi, Y., Katagiri, S., Nagano, M. and Ishikawa, A. (2001). In vitro growth of mouse ovarian preantral follicles and the capacity of their oocytes to develop to the blastocyst stage. Journal of Veterinary Medical Science, 63(6), 619624. doi: 10.1292/jvms.63.619 CrossRefGoogle Scholar
Braw-Tal, R. and Roth, Z. (2005). Gene expression for LH receptor, 17 alpha-hydroxylase and StAR in the theca interna of preantral and early antral follicles in the bovine ovary. Reproduction, 129(4), 453461. doi: 10.1530/rep.1.00464 CrossRefGoogle ScholarPubMed
Bulgarelli, D. L., Ting, A. Y., Gordon, B. J., de Sá Rosa-e-Silva, A. C. J. and Zelinski, M. B. (2018). Development of macaque secondary follicles exposed to neutral red prior to 3-dimensional culture. Journal of Assisted Reproduction and Genetics, 35(1), 7179. doi: 10.1007/s10815-017-1043-y CrossRefGoogle ScholarPubMed
Buratini, J. J., Pinto, M. G. L., Castilho, A. C., Amorim, R. L., Giometti, I. C., Portela, V. M., Nicola, E. S. and Price, C. A. (2007). Expression and function of fibroblast growth factor 10 and its receptor, fibroblast growth factor receptor 2b, in bovine follicles. Biology of Reproduction, 77(4), 743750. doi: 10.1095/biolreprod.107.062273 CrossRefGoogle ScholarPubMed
Cadenas, J., Leiva-Revilla, J., Vieira, L. A., Apolloni, L. B., Aguiar, F. L. N., Alves, B. G., Lobo, C. H., Rodrigues, A. P. R., Apgar, G. A., Smitz, J., Figueiredo, J. R. and Maside, C. (2017). Caprine ovarian follicle requirements differ between preantral and early antral stages after IVC in medium supplemented with GH and VEGF alone or in combination. Theriogenology, 87(321), 321332. doi: 10.1016/j.theriogenology.2016.09.008 CrossRefGoogle ScholarPubMed
Camp, T. A., Rahal, J. O. and Mayo, K. E. (1991). Cellular localization and hormonal regulation of follicle-stimulating hormone and luteinizing hormone receptor messenger RNAs in the rat ovary. Molecular Endocrinology, 5(10), 14051417. doi: 10.1210/mend-5-10-1405 CrossRefGoogle ScholarPubMed
Campbell, B. K., Clinton, M. and Webb, R. (2012). The role of anti-Müllerian hormone (AMH) during follicle development in a monovulatory species (sheep). Endocrinology, 153(9), 45334543. doi: 10.1210/en.2012-1158 CrossRefGoogle Scholar
Cao, L., Li, S., Huang, S., Shi, D. and Li, X. (2021). AQP8 participates in oestrogen-mediated buffalo follicular development by regulating apoptosis of granulosa cells. Reproduction in Domestic Animals, 56(5), 812820. doi: 10.1111/rda.13921 CrossRefGoogle ScholarPubMed
Carson, R. and Smith, J. (1986). Development and steroidogenic activity of preantral follicles in the neonatal rat ovary. Journal of Endocrinology, 110(1), 8792. doi: 10.1677/joe.0.1100087 CrossRefGoogle ScholarPubMed
Celestino, J. J. H., Lima-Verde, I. B., Bruno, J. B., Matos, M. H. T., Chaves, R. N., Saraiva, M. V. A., Silva, C. M. G., Faustino, L. R., Rossetto, R., Lopes, C. A. P., Donato, M. A. M., Peixoto, C. A., Campello, C. C., Silva, J. R. V. and Figueiredo, J. R. (2011). Steady-state level of bone morphogenetic protein-15 in goat ovaries and its influence on in vitro development and survival of preantral follicles. Molecular and Cellular Endocrinology, 338(1–2), 19. doi: 10.1016/j.mce.2011.02.007 CrossRefGoogle ScholarPubMed
Chansaenroj, A., Songsasen, N. and Chatdarong, K. (2019). Equine chorionic gonadotropin induces in vitro follicular growth from the multi-layered secondary developmental stage in cats. Theriogenology, 123, 116122. doi: 10.1016/j.theriogenology.2018.09.040 CrossRefGoogle ScholarPubMed
Chiti, M. C., Dolmans, M. M., Hobeika, M., Cernogoraz, A., Donnez, J. and Amorim, C. A. (2017). A modified and tailored human follicle isolation procedure improves follicle recovery and survival. Journal of Ovarian Research, 10(1), 71. doi: 10.1186/s13048-017-0366-8 CrossRefGoogle ScholarPubMed
Chu, Y. L., Xu, Y. R., Yang, W. X. and Sun, Y. (2018). The role of FSH and TGF-β superfamily in follicle atresia. Aging, 10(3), 305321. doi: 10.18632/aging.101391 CrossRefGoogle ScholarPubMed
Clarke, H. G., Hope, S. A., Byers, S. and Rodgers, R. J. (2006). Formation of ovarian follicular fluid may be due to the osmotic potential of large glycosaminoglycans and proteoglycans. Reproduction, 132(1), 119131. doi: 10.1530/rep.1.00960 CrossRefGoogle Scholar
da Cunha, E. V., Melo, L. R. F., Sousa, G. B., Araújo, V. R., Vasconcelos, G. L., Silva, A. W. B. and Silva, J. R. V. (2018). Effect of bone morphogenetic proteins 2 and 4 on survival and development of bovine secondary follicles cultured in vitro . Theriogenology, 110, 4451. doi: 10.1016/j.theriogenology.2017.12.032 CrossRefGoogle ScholarPubMed
da Silva, G. M., Rossetto, R., Chaves, R. N., Duarte, A. B. G., Araújo, V. R., Feltrin, C., Bernuci, M. P., Anselmo-Franci, J. A., Xu, M., Woodruff, T. K., Campello, C. C. and Figueiredo, J. R. (2015). In vitro development of secondary follicles from pre-pubertal and adult goats cultured in two-dimensional or three-dimensional systems. Zygote, 23(4), 475484. doi: 10.1017/S0967199414000070 CrossRefGoogle Scholar
De Conto, E., Matte, U. and Cunha-Filho, J. S. (2021). BMP-6 and SMAD4 gene expression is altered in cumulus cells from women with endometriosis-associated infertility. Acta Obstetricia et Gynecologica Scandinavica, 100(5), 868875. doi: 10.1111/aogs.13931 CrossRefGoogle ScholarPubMed
de Figueiredo, J. R. and de Lima, L. F. (2017). Artificial ovary technology: Applications, state of art, limitations and prospects. Revista Brasileira de Reprodução Animal, 41(1), 248253.Google Scholar
de Figueiredo, J. R., de Lima, L. F., Silva, J. R. V. and Santos, R. R. (2018). Control of growth and development of preantral follicle: Insights from in vitro culture. Animal Reproduction, 15 Suppl. 1, 648659. doi: 10.21451/1984-3143-AR2018-0019 CrossRefGoogle Scholar
de Figueiredo, J. R., Cadenas, J., de Lima, L. F. and Santos, R. R. (2020). Advances in in vitro folliculogenesis in domestic ruminants. Animal Reproduction, 16(1), 5265. doi: 10.21451/1984-3143-AR2018-123 CrossRefGoogle ScholarPubMed
de Lima, L. F., Rubessa, M., Rocha, R. M. P., Winters, R., Milner, D. J., Campello, C. C., Figueiredo, J. R. and Wheeler, M. B. (2017). High diluted and dynamised follicle stimulating hormone modulates steroid production in isolated porcine preantral follicles cultured in vitro . Homeopathy, 106(2), 8792. doi: 10.1016/j.homp.2017.03.004 Google ScholarPubMed
Dumesic, D. A., Meldrum, D. R., Katz-Jaffe, M. G., Krisher, R. L. and Schoolcraft, W. B. (2015). Oocyte environment: Follicular fluid and cumulus cells are critical for oocyte health. Fertility and Sterility, 103(2), 303316. doi: 10.1016/j.fertnstert.2014.11.015 CrossRefGoogle ScholarPubMed
Durlej, M., Knapczyk-Stwora, K., Duda, M., Galas, J. and Slomczynska, M. (2011). The expression of FSH receptor (FSHR) in the neonatal porcine ovary and its regulation by flutamide. Reproduction in Domestic Animals, 46(3), 377384. doi: 10.1111/j.1439-0531.2010.01673.x CrossRefGoogle ScholarPubMed
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., Asara, J. M., Fitzpatrick, J., Dillin, A., Viollet, B., Kundu, M., Hansen, M. and Shaw, R. J. (2011). Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science, 331(6016), 456461. doi: 10.1126/science.1196371 CrossRefGoogle ScholarPubMed
Emerling, B. M., Weinberg, F., Snyder, C., Burgess, Z., Mutlu, G. M., Viollet, B., Budinger, G. R. and Chandel, N. S. (2009). Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratio. Free Radical Biology and Medicine, 46(10), 13861391. doi: 10.1016/j.freeradbiomed.2009.02.019 CrossRefGoogle ScholarPubMed
Eppig, J. J. and O’Brien, M. J. (1996). Development in vitro of mouse oocytes from primordial follicles. Biology of Reproduction, 54(1), 197207. doi: 10.1095/biolreprod54.1.197 CrossRefGoogle ScholarPubMed
Ferreira, A. C. A., Cadenas, J., , N. A. R., Correia, H. H. V., Guerreiro, D. D., Lobo, C. H., Alves, B. G., Maside, C., Gastal, E. L., Rodrigues, A. P. R. and Figueiredo, J. R. (2018). In vitro culture of isolated preantral and antral follicles of goats using human recombinant FSH: Concentration-dependent and stage-specific effect. Animal Reproduction Science, 196, 120129. doi: 10.1016/j.anireprosci.2018.07.004 CrossRefGoogle ScholarPubMed
Fitzpatrick, S. L. and Richards, J. S. (1994). Identification of a cyclic adenosine 3′, 5′-monophosphate-response element in the rat aromatase promoter that is required for transcriptional activation in rat granulosa cells and R2C leydig cells. Molecular Endocrinology, 8(10), 13091319. doi: 10.1210/mend.8.10.7854348 Google ScholarPubMed
Forrest, K. K., Flores, V. V., Gurule, S. C., Soto-Navarro, S., Shuster, C. B., Gifford, C. A. and Gifford, J. A. H. (2022). Effects of lipopolysaccharide on follicular estrogen production and developmental competence in bovine oocytes. Animal Reproduction Science, 237, 106927. doi: 10.1016/j.anireprosci.2022.106927 CrossRefGoogle ScholarPubMed
Frota, I. M. A., Silva, J. R. V., Leitão, C. C. F. and Brito, I. R. (2009). Importance of local growth factors in the regulation of ovarian folliculogenesis in mammals. Acta Scientiae Veterinariae, 37(3), 215224.Google Scholar
Frota, I. M., Leitao, C. C., Costa, J. J., Van den Hurk, R., Brito, I. R., Saraiva, M. V. A., Figueiredo, J. R. and Silva, J. R. V. (2011). Effects of BMP-7 and FSH on the development of goat preantral follicles and levels of mRNA for FSH-R, BMP-7 and BMP receptors after in-vitro culture. Animal Reproduction, 8(1–2), 2531.Google Scholar
Fushii, M., Yamada, R. and Miyano, T. (2021). In vitro growth of bovine oocytes in oocyte-cumulus cell complexes and the effect of follicle stimulating hormone on the growth of oocytes. Journal of Reproduction and Development, 67(1), 513. doi: 10.1262/jrd.2020-102 CrossRefGoogle ScholarPubMed
Gannon, A. M., Stämpfli, M. R. and Foster, W. G. (2012). Cigarette smoke exposure leads to follicle loss via an alternative ovarian cell death pathway in a mouse model. Toxicological Sciences, 125(1), 274284. doi: 10.1093/toxsci/kfr279 CrossRefGoogle ScholarPubMed
García-Guerra, A., Canavessi, A. M. O., Monteiro, P. L. J. Jr, Mezera, M. A., Sartori, R., Kirkpatrick, B. W. and Wiltbank, M. C. (2018). Trio, a novel bovine high fecundity allele: III. Acquisition of dominance and ovulatory capacity at a smaller follicle size. Biology of Reproduction, 98(3), 350365. doi: 10.1093/biolre/iox157 Google Scholar
Gautam, D., Vats, A., Pal, P., Haldar, A. and De, S. (2021). Characterization of anti-Müllerian hormone (AMH) gene in buffaloes and goats. Frontiers in Veterinary Science, 8, 627094. doi: 10.3389/fvets.2021.627094 CrossRefGoogle ScholarPubMed
Ghorbani, S., Eyni, H., Norahan, M. H., Zarrintaj, P., Urban, N., Mohammadzadeh, A., Mostafavi, E. and Sutherland, D. S. (2022). Advanced bioengineering of female germ cells to preserve fertility. Biology of Reproduction, 107(5), 11771204. doi: 10.1093/biolre/ioac160 Google ScholarPubMed
Ginther, O. J., Beg, M. A., Bergfelt, D. R., Donadeu, F. X. and Kot, K. (2001). Follicle selection in monovular species. Biology of Reproduction, 65(3), 638647. doi: 10.1095/biolreprod65.3.638 CrossRefGoogle ScholarPubMed
Glister, C., Kemp, C. F. and Knight, P. G. (2004). Bone morphogenetic protein (BMP) ligands and receptors in bovine ovarian follicle cells: Actions of BMP-4, -6 and -7 on granulosa cells and differential modulation of Smad-1 phosphorylation by follistatin. Reproduction, 127(2), 239254. doi: 10.1530/rep.1.00090 CrossRefGoogle ScholarPubMed
Gomes, F. D. R., de Brito, D. C. C., de Sá, N. A. R., Ñaupas, L. V. S., Palomino, G. J. Q., da Silva, R. F., Lopes, É. P. F., Mbemya, G. T., Alves, B. G., Zelinski, M., de Figueiredo, J. R. and Rodrigues, A. P. R. (2022). Development of sheep secondary follicles and preservation of aromatase and metalloproteinases 2 and 9 after vitrification and in vitro culture. Cell and Tissue Banking, 23(2), 247259. doi: 10.1007/s10561-021-09937-5 CrossRefGoogle ScholarPubMed
Gordy, C. and He, Y. W. (2012). The crosstalk between autophagy and apoptosis: Where does this lead? Protein and Cell, 3(1), 1727. doi: 10.1007/s13238-011-1127-x CrossRefGoogle ScholarPubMed
Green, L. J. and Shikanov, A. (2016). In vitro culture methods of preantral follicles. Theriogenology, 86(1), 229238. doi: 10.1016/j.theriogenology.2016.04.036 CrossRefGoogle ScholarPubMed
Hao, J., Tuck, A. R., Prakash, C. R., Damdimopoulos, A., Sjödin, M. O. D., Lindberg, J., Niklasson, B., Pettersson, K., Hovatta, O. and Damdimopoulou, P. (2020). Culture of human ovarian tissue in xeno-free conditions using laminin components of the human ovarian extracellular matrix. Journal of Assisted Reproduction and Genetics, 37(9), 21372150. doi: 10.1007/s10815-020-01886-4 CrossRefGoogle ScholarPubMed
Healy, M. W., Dolitsky, S. N., Villancio-Wolter, M., Raghavan, M., Tillman, A. R., Morgan, N. Y., DeCherney, A. H., Park, S. and Wolff, E. F. (2021). Creating an artificial 3-dimensional ovarian follicle culture system using a microfluidic system. Micromachines, 12(3), 261. doi: 10.3390/mi12030261 CrossRefGoogle ScholarPubMed
Huang, C. T., Weitsman, S. R., Dykes, B. N. and Magoffin, D. A. (2001). Stem cell factor and insulin-like growth factor-I stimulate luteinizing hormone-independent differentiation of rat ovarian theca cells. Biology of Reproduction, 64(2), 451456. doi: 10.1095/biolreprod64.2.451 CrossRefGoogle ScholarPubMed
Iber, D. and Geyter, C. D. (2013). Computational modelling of bovine ovarian follicle development. BMC Systems Biology, 7, 60. doi: 10.1186/1752-0509-7-60 CrossRefGoogle ScholarPubMed
Ishibashi, K., Hara, S. and Kondo, S. (2009). Aquaporin water channels in mammals. Clinical and Experimental Nephrology, 13(2), 107117. doi: 10.1007/s10157-008-0118-6 CrossRefGoogle ScholarPubMed
Ismail, R. S., Dubé, M. and Vanderhyden, B. C. (1997). Hormonally regulated expression and alternative splicing of kit ligand may regulate kit-induced inhibition of meiosis in rat oocytes. Developmental Biology, 184(2), 333342. doi: 10.1006/dbio.1997.8531 CrossRefGoogle ScholarPubMed
Jachter, S. L., Simmons, W. P., Estill, C., Xu, J. and Bishop, C. V. (2022). Matrix-free three-dimensional culture of bovine secondary follicles to antral stage: Impact of media formulation and epidermal growth factor (EGF). Theriogenology, 181, 8994. doi: 10.1016/j.theriogenology.2022.01.013 CrossRefGoogle ScholarPubMed
Kawashima, I. and Kawamura, K. (2018). Regulation of follicle growth through hormonal factors and mechanical cues mediated by Hippo signaling pathway. Systems Biology in Reproductive Medicine, 64(1), 311. doi: 10.1080/19396368.2017.1411990 CrossRefGoogle ScholarPubMed
Kayamori, T., Kosaka, N., Miyamoto, A. and Shimizu, T. (2009). The differential pathways of bone morphogenetic protein (BMP)-4 and -7 in the suppression of the bovine granulosa cell apoptosis. Molecular and Cellular Biochemistry, 323(1–2), 161168. doi: 10.1007/s11010-008-9976-1 CrossRefGoogle ScholarPubMed
Kere, M., Liu, P. C., Chen, Y. K., Chao, P. C., Tsai, L. K., Yeh, T. Y., Siriboon, C., Intawicha, P., Lo, N. W., Chiang, H. I., Fan, Y. K. and Ju, J. C. (2020). Ultrastructural characterization of porcine growing and in vitro matured oocytes. Animals: An Open Access Journal from MDPI, 10(4), 116. doi: 10.3390/ani10040664 CrossRefGoogle ScholarPubMed
Khunmanee, S. and Park, H. (2022). Three-dimensional culture for in vitro folliculogenesis in the aspect of methods and materials. Tissue Engineering. Part B, Reviews, 28(6), 12421257. doi: 10.1089/ten.TEB.2021.0229 CrossRefGoogle ScholarPubMed
Kim, J., Kundu, M., Viollet, B. and Guan, K. L. (2011). AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature Cell Biology, 13(2), 132141. doi: 10.1038/ncb2152 CrossRefGoogle ScholarPubMed
Lima, I. M. T., Brito, I. R., Rodrigues, G. Q., Silva, C. M. G., Magalhães-Padilha, D. M., Lima, L. F., Celestino, J. J. H., Campello, C. C., Silva, J. R. V., Figueiredo, J. R. and Rodrigues, A. P. R. (2011). Presence of c-kit mRNA in goat ovaries and improvement of in vitro preantral follicle survival and development with kit ligand. Molecular and Cellular Endocrinology, 345(1–2), 3847. doi: 10.1016/j.mce.2011.07.006 CrossRefGoogle ScholarPubMed
Lins, T. L. B. G., Cavalcante, A. Y. P., Santos, J. M. S., Menezes, V. G., Barros, V. R. P., Barberino, R. S., Bezerra, M. É. S., Macedo, T. J. S. and Matos, M. H. T. (2017). Rutin can replace the use of three other antioxidants in the culture medium, maintaining the viability of sheep isolated secondary follicles. Theriogenology, 89, 263270. doi: 10.1016/j.theriogenology.2016.11.019 CrossRefGoogle ScholarPubMed
Ma, L., Tang, X., Guo, S., Liang, M., Zhang, B. and Jiang, Z. (2020). miRNA-21-3p targeting of FGF2 suppresses autophagy of bovine ovarian granulosa cells through AKT/mTOR pathway. Theriogenology, 157, 226237. doi: 10.1016/j.theriogenology.2020.06.021 CrossRefGoogle ScholarPubMed
Macedo, T. J. S., Santos, J. M. S., Bezerra, M. É. S., Menezes, V. G., Gouveia, B. B., Barbosa, L. M. R., Lins, T. L. B. G., Monte, A. P. O., Barberino, R. S., Batista, A. M., Barros, V. R. P., Wischral, A., Queiroz, M. A. A., Araújo, G. G. L. and Matos, M. H. T. (2019). Immunolocalization of leptin and its receptor in the sheep ovary and in vitro effect of leptin on follicular development and oocyte maturation. Molecular and Cellular Endocrinology, 495, 110506. doi: 10.1016/j.mce.2019.110506 CrossRefGoogle ScholarPubMed
Magoffin, D. A. and Weitsman, S. R. (1994). Insulin-like growth factor-I regulation of luteinizing hormone (LH) receptor messenger ribonucleic acid expression and LH-stimulated signal transduction in rat ovarian theca-interstitial cells. Biology of Reproduction, 51(4), 766775. doi: 10.1095/biolreprod51.4.766 CrossRefGoogle ScholarPubMed
Makarevich, A. V., Földešiová, M., Pivko, J., Kubovičová, E. and Chrenek, P. (2018). Histological characteristics of ovarian follicle atresia in dairy cows with different milk production. Anatomia, Histologia, Embryologia, 47(6), 510516. doi: 10.1111/ahe.12389 CrossRefGoogle ScholarPubMed
Mbemya, G. T., de Sá, N. A. R., Guerreiro, D. D., de Sousa, F. G. C., Nguedia, S. N., Alves, B. G., Santos, F. W., Pessoa, O. D. L., Comizzoli, P., Figueiredo, J. R. and Rodrigues, A. P. R. (2019). Early ovine preantral follicles have a potential to grow until antral stage in two-step culture system in the presence of aqueous extract of Justicia insularis . Reproduction in Domestic Animals, 54(8), 11211130. doi: 10.1111/rda.13477 CrossRefGoogle ScholarPubMed
McGee, E. A., Chun, S. Y., Lai, S., He, Y. E. and Hsueh, A. J. (1999). Keratinocyte growth factor promotes the survival, growth, and differentiation of preantral ovarian follicles. Fertility and Sterility, 71(4), 732738. doi: 10.1016/s0015-0282(98)00547-0 CrossRefGoogle ScholarPubMed
Méduri, G., Charnaux, N., Driancourt, M. A., Combettes, L., Granet, P., Vannier, B., Loosfelt, H. and Milgrom, E. (2002). Follicle-stimulating hormone receptors in oocytes? Journal of Clinical Endocrinology and Metabolism, 87(5), 22662276. doi: 10.1210/jcem.87.5.8502 CrossRefGoogle ScholarPubMed
Meng, L., Jan, S. Z., Hamer, G., van Pelt, A. M., van der Stelt, I., Keijer, J. and Teerds, K. J. (2018). Preantral follicular atresia occurs mainly through autophagy, while antral follicles degenerate mostly through apoptosis. Biology of Reproduction, 99(4), 853863. doi: 10.1093/biolre/ioy116 Google ScholarPubMed
Monte, A. P. O., Santos, J. M., Menezes, V. G., Gouveia, B. B., Lins, T. L. B. G., Barberino, R. S., Oliveira, J. L., Donfack, N. J. and Matos, M. H. T. (2019). Growth differentiation factor-9 improves development, mitochondrial activity and meiotic resumption of sheep oocytes after in vitro culture of secondary follicles. Reproduction in Domestic Animals, 54(9), 11691176. doi: 10.1111/rda.13485 CrossRefGoogle ScholarPubMed
Nagyova, E., Salustri, A., Nemcova, L., Scsukova, S., Kalous, J. and Camaioni, A. (2020). Versican G1 fragment establishes a strongly stabilized interaction with hyaluronan-rich expanding matrix during oocyte maturation. International Journal of Molecular Sciences, 21(7), 114. doi: 10.3390/ijms21072267 CrossRefGoogle ScholarPubMed
Nuttinck, F., Collette, L., Massip, A. and Dessy, F. (1996). Histologic and autoradiographic study of the in vitro effects of FGF-2 and FSH on isolated bovine preantral follicles: Preliminary investigation. Theriogenology, 45(6), 12351245. doi: 10.1016/0093-691x(96)00078-7 CrossRefGoogle ScholarPubMed
O’Brien, M. J., Pendola, J. K. and Eppig, J. J. (2003). A revised protocol for in vitro development of mouse oocytes from primordial follicles dramatically improves their developmental competence. Biology of Reproduction, 68(5), 16821686. doi: 10.1095/biolreprod.102.013029 CrossRefGoogle ScholarPubMed
Oktay, K., Briggs, D. and Gosden, R. G. (1997). Ontogeny of follicle-stimulating hormone receptor gene expression in isolated human ovarian follicles. Journal of Clinical Endocrinology and Metabolism, 82(11), 37483751. doi: 10.1210/jcem.82.11.4346 Google ScholarPubMed
Orisaka, M., Hattori, K., Fukuda, S., Mizutani, T., Miyamoto, K., Sato, T., Tsang, B. K., Kotsuji, F. and Yoshida, Y. (2013). Dysregulation of ovarian follicular development in female rat: LH decreases FSH sensitivity during preantral-early antral transition. Endocrinology, 154(8), 28702880. doi: 10.1210/en.2012-2173 CrossRefGoogle ScholarPubMed
Orisaka, M., Orisaka, S., Jiang, J. Y., Craig, J., Wang, Y., Kotsuji, F. and Tsang, B. K. (2006). Growth differentiation factor 9 is antiapoptotic during follicular development from preantral to early antral stage. Molecular Endocrinology, 20(10), 24562468. doi: 10.1210/me.2005-0357 CrossRefGoogle ScholarPubMed
Orisaka, M., Jiang, J. Y., Orisaka, S., Kotsuji, F. and Tsang, B. K. (2009a). Growth differentiation factor 9 promotes rat preantral follicle growth by up-regulating follicular androgen biosynthesis. Endocrinology, 150(6), 27402748. doi: 10.1210/en.2008-1536 CrossRefGoogle ScholarPubMed
Orisaka, M., Tajima, K., Tsang, B. K. and Kotsuji, F. (2009b). Oocyte-granulosa-theca cell interactions during preantral follicular development. Journal of Ovarian Research, 2(1), 9. doi: 10.1186/1757-2215-2-9 CrossRefGoogle ScholarPubMed
Panta, A. M. T., Silva, A. F. B. D., Padilha, R. T., Correia, H. H. V., Rondina, D., Figueiredo, J. R. and Magalhães Padilha, D. M. (2019). Evaluation of in vitro culture systems for goat preantral follicles using reused ovaries from reproductive biotechniques: An alternative to maximize the potential of reproduction. Reproduction in Domestic Animals, 54(3), 480485. doi: 10.1111/rda.13377 CrossRefGoogle ScholarPubMed
Parrott, J. A. and Skinner, M. K. (1998). Thecal cell-granulosa cell interactions involve a positive feedback loop among keratinocyte growth factor, hepatocyte growth factor, and Kit ligand during ovarian follicular development. Endocrinology, 139(5), 22402245. doi: 10.1210/endo.139.5.6018 CrossRefGoogle ScholarPubMed
Parrott, J. A. and Skinner, M. K. (2000). Kit ligand actions on ovarian stromal cells: Effects on theca cell recruitment and steroid production. Molecular Reproduction and Development, 55(1), 5564. doi: 10.1002/(SICI)1098-2795(200001)55:1<55::AID-MRD8>3.0.CO;2-L3.0.CO;2-L>CrossRefGoogle ScholarPubMed
Passos, M. J., Vasconcelos, G. L., Silva, A. W., Brito, I. R., Saraiva, M. V., Magalhães, D. M., Costa, J. J., Donato, M. A., Ribeiro, R. P., Cunha, E. V., Peixoto, C. A., Campello, C. C., Figueiredo, J. R., van den Hurk, R. and Silva, J. R. (2013). Accelerated growth of bovine preantral follicles in vitro after stimulation with both FSH and BMP-15 is accompanied by ultrastructural changes and increased atresia. Theriogenology, 79(9), 12691277. doi: 10.1016/j.theriogenology.2013.02.023 CrossRefGoogle ScholarPubMed
Paulini, F., Araujo, M. S., Silva, L. P. and Lucci, C. M. (2022). Initial steps on mapping differentially expressed proteins in bovine preantral follicles and ovarian tissue: An approach using single-follicle MALDI-MS and mass spectrometry imaging (MSI) analysis. Reproduction in Domestic Animals, 57(1), 1932. doi: 10.1111/rda.14025 CrossRefGoogle ScholarPubMed
Paulino, L. R. F. M., Cunha, E. V., Barbalho Silva, A. W., Souza, G. B., Lopes, E. P. F., Donato, M. A. M., Peixoto, C. A., Matos-Brito, B. G., van den Hurk, R. and Silva, J. R. V. (2018). Effects of tumour necrosis factor-alpha and interleukin-1 beta on in vitro development of bovine secondary follicles. Reproduction in Domestic Animals, 53(4), 9971005. doi: 10.1111/rda.13199 CrossRefGoogle ScholarPubMed
Paulino, L. R. F. M., Barroso, P. A. A., Silva, A. W. B., Souza, A. L. P., Bezerra, F. T. G., Silva, B. R., Donato, M. M. A., Peixoto, C. A. and Silva, J. R. V. (2020). Effects of epidermal growth factor and progesterone on development, ultrastructure and gene expression of bovine secondary follicles cultured in vitro . Theriogenology, 142, 284290. doi: 10.1016/j.theriogenology.2019.10.031 CrossRefGoogle ScholarPubMed
Paulino, L. R. F. M., de Assis, E. I. T., Azevedo, V. A. N., Silva, B. R., da Cunha, E. V. and Silva, J. R. V. (2022). Why is it so difficult to have competent oocytes from in vitro cultured preantral follicles? Reproductive Sciences, 29(12), 33213334. doi: 10.1007/s43032-021-00840-8 CrossRefGoogle ScholarPubMed
Paz, M. P., de Sousa, F. G. C., Alves, B. G., Lobo, C. H., Sales, A. D., Tavares, K. C. S., de Sá, N. A. R., Guerreiro, D. D., Maside, C., Rocha, R. M. P., Bertolini, L. R., Bordignon, V., de Figueiredo, J. R. and Rodrigues, A. P. R. (2018). Effect of aquaporin 3 knockdown by RNA interference on antrum formation in sheep secondary follicles cultured in vitro . Zygote, 26(5), 350358. doi: 10.1017/S096719941800031X CrossRefGoogle ScholarPubMed
Pontes, L. M. S., Gouveia, B. B., Menezes, V. G., de Barros, V. R. P., Barberino, R. S., do Monte, A. P. O., Donfack, N. J., Celestino, J. J. H., Salgueiro, C. C. M., de Figueiredo, J. R. and de Matos, M. H. T. (2019). Supplemented powdered coconut water (ACP-406®) promotes growth of goat secondary follicles and oocyte meiotic resumption. Animal Reproduction, 16(4), 819828. doi: 10.21451/1984-3143-AR2019-0008 CrossRefGoogle ScholarPubMed
Reineri, P. S., Coria, M. S., Barrionuevo, M. G., Hernández, O., Callejas, S. and Palma, G. A. (2018). Gene expression of growth factor BMP15, GDF9, FGF2 and their receptors in bovine follicular cells. Revista MVZ Córdoba, 23(3), 67786787. doi: 10.21897/rmvz.1367 CrossRefGoogle Scholar
Riaz, H., Yousuf, M. R., Liang, A., Hua, G. H. and Yang, L. (2019). Effect of melatonin on regulation of apoptosis and steroidogenesis in cultured buffalo granulosa cells. Animal Science Journal, 90(4), 473480. doi: 10.1111/asj.13152 CrossRefGoogle ScholarPubMed
Rocha, R. M. P., Rubessa, M., de Lima, L. F., da Silva, A. F. B., Winters, R., Polkoff, K., Milner, D., Campello, C. C., de Figueiredo, J. R. and Wheeler, M. (2021). Effect of base media, FSH and anti-Müllerian hormone (AMH) alone or in combination on the growth of pig preantral follicles in vitro . Research, Society and Development, 10(15), e53101522488. doi: 10.33448/rsd-v10i15.22488 CrossRefGoogle Scholar
Rodgers, R. J. and Irving-Rodgers, H. F. (2010). Formation of the ovarian follicular antrum and follicular fluid. Biology of Reproduction, 82(6), 10211029. doi: 10.1095/biolreprod.109.082941 CrossRefGoogle ScholarPubMed
Russell, D. L. and Robker, R. L. (2018). Cumulus cells. In: Skinner, M. K. (ed.) Encyclopedia of Reproduction, 2nd edition vol. 2, Academic Press, pp. 4346. doi: 10.1016/B978-0-12-801238-3.64392-1 CrossRefGoogle Scholar
Sabbah, D. A., Hajjo, R. and Sweidan, K. (2020). Review on epidermal growth factor receptor (EGFR) structure, signaling pathways, interactions, and recent updates of EGFR inhibitors. Current Topics in Medicinal Chemistry, 20(10), 815834. doi: 10.2174/1568026620666200303123102 CrossRefGoogle ScholarPubMed
Sakaguchi, K., Huang, W., Yang, Y., Yanagawa, Y. and Nagano, M. (2017). Relationship between in vitro growth of bovine oocytes and steroidogenesis of granulosa cells cultured in medium supplemented with bone morphogenetic protein-4 and follicle stimulating hormone. Theriogenology, 97, 113123. doi: 10.1016/j.theriogenology.2017.04.030 CrossRefGoogle ScholarPubMed
Sales, A. D., Duarte, A. B. G., Rodrigues, G. Q., Lima, L. F., Silva, G. M., Carvalho, A. A., Brito, I. R., da Maranguape, R. M. S., Lobo, C. H., Aragão, J. A. S., Moura, A. A., Figueiredo, J. R. and Rodrigues, A. P. R. (2015). Steady-state level of messenger RNA and immunolocalization of aquaporins 3, 7, and 9 during in vitro growth of ovine preantral follicles. Theriogenology, 84(1), 110. doi: 10.1016/j.theriogenology.2015.01.005 CrossRefGoogle ScholarPubMed
Santos, J. M. S., Monte, A. P. O., Lins, T. L. B. G., Barberino, R. S., Menezes, V. G., Gouveia, B. B., Macedo, T. J. S., Oliveira Júnior, J. L., Donfack, N. J. and Matos, M. H. T. (2019). Kaempferol can be used as the single antioxidant in the in vitro culture medium, stimulating sheep secondary follicle development through the phosphatidylinositol 3-kinase signaling pathway. Theriogenology, 136, 8694. doi: 10.1016/j.theriogenology.2019.06.036 CrossRefGoogle ScholarPubMed
Saraiva, M. V. A., Celestino, J. J. H., Araújo, V. R., Chaves, R. N., Almeida, A. P., Lima-Verde, I. B., Duarte, A. B. G., Silva, G. M., Martins, F. S., Bruno, J. B., Matos, M. H. T., Campello, C. C., Silva, J. R. V. and Figueiredo, J. R. (2011). Expression of follicle-stimulating hormone receptor (FSHR) in goat ovarian follicles and the impact of sequential culture medium on in vitro development of caprine preantral follicles. Zygote, 19(3), 205214. doi: 10.1017/S0967199410000511 CrossRefGoogle ScholarPubMed
Schoenfelder, M. and Einspanier, R. (2003). Expression of hyaluronan synthases and corresponding hyaluronan receptors is differentially regulated during oocyte maturation in cattle. Biology of Reproduction, 69(1), 269277. doi: 10.1095/biolreprod.102.011577 CrossRefGoogle ScholarPubMed
Seneda, M. M., Bergamo, L. Z., González, S. M., Zangirolamo, A. F. and Morotti, F. (2021). Oogênese e Foliculogênese em bovinos. Revista Brasileira de Reprodução Animal, 45(4), 323328. doi: 10.21451/1809-3000.RBRA2021.042 CrossRefGoogle Scholar
Sharma, G. T., Dubey, P. K. and Kumar, G. S., and Kumar. (2011) Localization and expression of follicle-stimulating hormone receptor gene in buffalo (Bubalus bubalis) pre-antral follicles. Reproduction in Domestic Animals, 46(1), 114120. doi: 10.1111/j.1439-0531.2010.01604.x CrossRefGoogle ScholarPubMed
Silva, A. W. B., Bezerra, F. T. G., Costa, J. J. N., Rossi, R. O. D. S., Passos, M. J., Vasconcelos, G. L., Rossetto, R., Donato, M. A. M., Magalhães-Padilha, D. M., Campello, C. C., Saraiva, M. V. A., Figueiredo, J. R., Peixoto, C. A., Van den Hurk, R. and Silva, J. R. V. (2014). Differential effects of activin-A and FSH on growth, viability and messenger RNA expression in cultured bovine preantral follicles. Livestock Science, 160(1), 199207. doi: 10.1016/j.livsci.2013.12.003 CrossRefGoogle Scholar
Silva, G. A. L., Araújo, L. B., Silva, L. C. R., Gouveia, B. B., Barberino, R. S., Lins, T. L. B. G., Monte, A. P. O., Macedo, T. J. S., Santos, J. M. S., Menezes, V. G., Silva, R. L. S. and Matos, M. H. T. (2021). Gallic acid promotes the in vitro development of sheep secondary isolated follicles involving the phosphatidylinositol 3-kinase pathway. Animal Reproduction Science, 230, 106767. doi: 10.1016/j.anireprosci.2021.106767 CrossRefGoogle ScholarPubMed
Simon, L. E., Kumar, T. R. and Duncan, F. E. (2020). In vitro ovarian follicle growth: A comprehensive analysis of key protocol variables. Biology of Reproduction, 103(3), 455470. doi: 10.1093/biolre/ioaa073 CrossRefGoogle ScholarPubMed
Skowronski, M. T., Kwon, T. H. and Nielsen, S. (2009). Immunolocalization of aquaporin 1, 5, and 9 in the female pig reproductive system. Journal of Histochemistry and Cytochemistry, 57(1), 6167. doi: 10.1369/jhc.2008.952499 CrossRefGoogle ScholarPubMed
Soares-Costa, M. A. A., Costa, J. J. N., Silva, A. W. B., Cunha, E. V., Paulino, L. R. F. M., Silva, B. R., Silva, A. L. C., van den Hurk, R. and Silva, J. R. V. (2018). Effects of frutalin and doxorubicin on growth, ultrastructure and gene expression in goat secondary follicles cultured in vitro . Research in Veterinary Science, 120, 3340. doi: 10.1016/j.rvsc.2018.08.006 CrossRefGoogle ScholarPubMed
Spicer, L. J., Aad, P. Y., Allen, D. T., Mazerbourg, S., Payne, A. H. and Hsueh, A. J. (2008). Growth differentiation factor 9 (GDF9) stimulates proliferation and inhibits steroidogenesis by bovine theca cells: Influence of follicle size on responses to GDF9. Biology of Reproduction, 78(2), 243253. doi: 10.1095/biolreprod.107.063446 CrossRefGoogle ScholarPubMed
Sugiura, K., Su, Y. Q., Diaz, F. J., Pangas, S. A., Sharma, S., Wigglesworth, K., O’Brien, M. J., Matzuk, M. M., Shimasaki, S. and Eppig, J. J. (2007). Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells. Development, 134(14), 25932603. doi: 10.1242/dev.006882 CrossRefGoogle ScholarPubMed
Tanaka, Y., Matsuzaki, T., Tanaka, N., Iwasa, T., Kuwahara, A. and Irahara, M. (2019). Activin effects on follicular growth in in vitro preantral follicle culture. Journal of Medical Investigation, 66(1), (165171). doi: 10.2152/jmi.66.165 CrossRefGoogle ScholarPubMed
Tanimoto, R., Sekii, K., Morohaku, K., Li, J., Pépin, D. and Obata, Y. (2021). Blocking estrogen-induced AMH expression is crucial for normal follicle formation. Development, 148(6), 18. doi: 10.1242/dev.197459 CrossRefGoogle ScholarPubMed
Tomaszewski, C. E., DiLillo, K. M., Baker, B. M., Arnold, K. B. and Shikanov, A. (2021). Sequestered cell-secreted extracellular matrix proteins improve murine folliculogenesis and oocyte maturation for fertility preservation. Acta Biomaterialia, 132, 313324. doi: 10.1016/j.actbio.2021.03.041 CrossRefGoogle ScholarPubMed
Umer, S., Zhao, S. J., Sammad, A., Weldegebriall Sahlu, B. W., Yunwei, P. and Zhu, H. (2019). AMH: Could it be used as a biomarker for fertility and superovulation in domestic animals? Genes, 10(12), 114. doi: 10.3390/genes10121009 CrossRefGoogle ScholarPubMed
Vasconcelos, G. L., Saraiva, M. V. A., Costa, J. J. N., Passos, M. J., Silva, A. W. B., Rossi, R. O. D. S., Portela, A. M. L. R., Duarte, A. B. G., Magalhães-Padilha, D. M., Campelo, C. C., Figueiredo, J. R., Van den Hurk, R. and Silva, J. R. (2013). Effects of growth differentiation factor-9 and FSH on in vitro development, viability and mRNA expression in bovine preantral follicles. Reproduction, Fertility, and Development, 25(8), 11941203. doi: 10.1071/RD12173 CrossRefGoogle ScholarPubMed
Vasconcelos, E. M., Costa, F. C., Azevedo, A. V. N., Barroso, P. A. A., de Assis, E. I. T., Paulino, L. R. F. M., Silva, B. R., Silva, A. W. B., Souza, A. L. P. and Silva, J. R. V. (2021). Eugenol influences the expression of messenger RNAs for superoxide dismutase and glutathione peroxidase 1 in bovine secondary follicles cultured in vitro . Zygote, 29(4), 301306. doi: 10.1017/S0967199420000908 CrossRefGoogle ScholarPubMed
Wu, J. and Tian, Q. (2007). Role of follicle stimulating hormone and epidermal growth factor in the development of porcine preantral follicle in vitro . Zygote (Cambridge, England), 15(3), 233240. doi: 10.1017/S0967199407004194 CrossRefGoogle ScholarPubMed
Xavier, S. E. C. and Freitas, O. F. M. N. (2021). Manejo dietético e suplementar na fisiopatologia da síndrome dos ovários policísticos. [Dietary and supplementary management in the pathophysiology of polycystic ovary syndrome.] Research, Society and Development, 10(15), e237101522975e237101522975. doi: 10.33448/rsd-v10i15.22975 CrossRefGoogle Scholar
Xu, J., Xu, M., Bernuci, M. P., Fisher, T. E., Shea, L. D., Woodruff, T. K., Zelinski, M. B. and Stouffer, R. L. (2013). Primate follicular development and oocyte maturation in vitro . Advances in Experimental Medicine and Biology, 761, 4367. doi: 10.1007/978-1-4614-8214-7_5 CrossRefGoogle ScholarPubMed
Xu, F., Lawson, M. S., Bean, Y., Ting, A. Y., Pejovic, T., De Geest, K., Moffitt, M., Mitalipov, S. M. and Xu, J. (2021). Matrix-free 3D culture supports human follicular development from the unilaminar to the antral stage in vitro yielding morphologically normal metaphase II oocytes. Human Reproduction (Oxford), 36(5), 13261338. doi: 10.1093/humrep/deab003 CrossRefGoogle Scholar
Young, J. M. and McNeilly, A. S. (2010). Theca: The forgotten cell of the ovarian follicle. Reproduction, 140(4), 489504. doi: 10.1530/REP-10-0094 CrossRefGoogle ScholarPubMed
Yuan, J. H., Wang, J. Z., Lan, G. C., Sui, H. S., Yu, J. N. and Tan, J. H. (2008). Expression of steroidogenic enzymes and synthesis of steroid hormones during development of ovarian follicles in prepubertal goats. Domestic Animal Endocrinology, 34(4), 451460. doi: 10.1016/j.domaniend.2008.01.002 CrossRefGoogle ScholarPubMed
Zeleznik, A. J. (2004). The physiology of follicle selection. Reproductive Biology and Endocrinology: RB&E, 2, 31. doi: 10.1186/1477-7827-2-31 CrossRefGoogle ScholarPubMed
Zhang, M. (2018). Oocyte meiotic arrest. In: Skinner, M. K. (ed.) Encyclopedia of Reproduction, 2nd edition vol. 3, Academic Press, pp. 153158. doi: 10.1016/B978-0-12-801238-3.64443-4 CrossRefGoogle Scholar
Zhang, J., Liu, Y., Yao, W., Li, Q., Liu, H. and Pan, Z. (2018). Initiation of follicular atresia: Gene networks during early atresia in pig ovaries. Reproduction, 156(1), 2333. doi: 10.1530/REP-18-0058 CrossRefGoogle ScholarPubMed
Zhou, H. and Zhang, Y. (2005). Effect of growth factors on in vitro development of caprine preantral follicle oocytes. Animal Reproduction Science, 90(3–4), 265272. doi: 10.1016/j.anireprosci.2005.01.008 CrossRefGoogle ScholarPubMed
Zoheir, K. M., Harisa, G. I., Allam, A. A., Yang, L., Li, X., Liang, A., Abd-Rabou, A. A. and Harrath, A. H. (2017). Effect of alpha lipoic acid on in vitro development of bovine secondary preantral follicles. Theriogenology, 88, 124130. doi: 10.1016/j.theriogenology.2016.09.013 CrossRefGoogle ScholarPubMed
Zoheir, K. M., Darwish, A. M., Liguo, Y. and Ashour, A. E. (2021). Transcriptome comparisons detect new genes associated with apoptosis of cattle and buffaloes preantral follicles. Journal of Genetic Engineering and Biotechnology, 19(1), 151. doi: 10.1186/s43141-021-00253-9 CrossRefGoogle ScholarPubMed
Figure 0

Figure 1. Factors that control the transition from preantral to early antral follicle.

Figure 1

Table 1. Role of growth factors in oocyte, granulosa and theca cells during the transition from preantral to early antral follicle

Figure 2

Figure 2. Hormones and growth factors that control the formation of the antral cavity during the transition from preantral to early antral follicles.

Figure 3

Figure 3. Mechanisms that control production of estradiol (E2) during the transition from preantral to early antral follicles.

Figure 4

Figure 4. Strategies to promote in vitro growth of preantral follicles.