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Combination of FSH and testosterone could enhance activation of primordial follicles and growth of activated follicles in 1-day-old mice ovaries in vitro cultured for 12 days

Published online by Cambridge University Press:  23 December 2024

Tahoura Torkzadeh
Affiliation:
Department of Theriogenology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
Zahra Asadi
Affiliation:
Department of Theriogenology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran Department of Oncology Science, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73014, USA
Mohammad Jafari Atrabi
Affiliation:
Institute of Pharmacology and Toxicology, University Medical Center, Georg August University, Göttingen, Germany Platform Degenerative Diseases, German Primate Center, Leibniz Institute for Primate Research (DPZ), Göttingen, Germany
Maryam Khodadi
Affiliation:
Department of Theriogenology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
Farideh Eivazkhani
Affiliation:
Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Samira Hajiaghalou
Affiliation:
Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Vahid Akbarinejad*
Affiliation:
Department of Theriogenology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
Rouhollah Fathi*
Affiliation:
Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
*
Corresponding authors: Vahid Akbarinejad; Email: [email protected], Rouhollah Fathi; Email: [email protected]
Corresponding authors: Vahid Akbarinejad; Email: [email protected], Rouhollah Fathi; Email: [email protected]

Abstract

Treatment with follicle-stimulating hormone (FSH) and testosterone (T2) and their combination have been observed to be influential on ovarian follicles of 1-day-old mice ovaries cultured for 8 days. Given that extension of the culture period could positively impact the development of follicles in cultured ovaries, the present study was conducted to evaluate the main and interaction effects of FSH by T2 on the development of ovarian follicles in 1-day-old mice ovaries cultured for 12 days. One-day-old mice ovaries were initially cultured with base medium for 4 days; thereafter, different hormonal treatments were added to the culture media, and the culture was continued for 8 additional days until day 12. Ovaries were collected for histological and molecular assessments on day 12. The greatest activation of primordial follicles and progression of activated follicles to the preantral stage was detected in ovaries treated with the combination of FSH and T2 (P < 0.05). This positive effect on the morphology of ovarian follicles was accompanied by upregulation of Pi3k, Gdf9, Bmp15, Cx37 and Fshr in the ovaries cultured with the combination of FSH and T2 (P < 0.05). Nonetheless, treatment with FSH and T2 led to a diminished proportion of intact follicles (P < 0.05), even though Bax/Bcl2 gene expression ratio, as an apoptotic index, was less in hormone-treated ovaries (P < 0.05). In conclusion, the combination of FSH and T2 could improve the activation of primordial follicles and the growth of activated follicles towards the preantral stage. This positive effect of FSH plus T2 appeared to be at least partly mediated through the upregulation of Pi3k and oocyte-derived growth factors including Gdf9 and Bmp15.

Type
Research Article
Copyright
© The Author(s), 2024. Published by Cambridge University Press

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Footnotes

ɸ

These authors equally contributed to the present study.

References

Alborzi, P., Jafari Atrabi, M., Akbarinejad, V., Khanbabaei, R. and Fathi, R. (2020) Incorporation of arginine, glutamine or leucine in culture medium accelerates in vitro activation of primordial follicles in 1-day-old mouse ovary. Zygote 28(5), 409416. https://doi.org/10.1017/s096719942000026x.CrossRefGoogle Scholar
Amorim, C.A. and Shikanov, A. (2016) The artificial ovary: current status and future perspectives. Future Oncology 12(20), 23232332. https://doi.org/10.2217/fon-2016-0202.CrossRefGoogle ScholarPubMed
Atrabi, M.J., Akbarinejad, V., Khanbabaee, R., Dalman, A., Amorim, C.A., Najar-Asl, M, Valojerdi, M.R. and Fathi, R. (2019) Formation and activation induction of primordial follicles using granulosa and cumulus cells conditioned media. Journal of Cellular Physiology 234(7), 1014810156. https://doi.org/10.1002/jcp.27681.CrossRefGoogle ScholarPubMed
Atrabi, M.J., Alborzi, P., Akbarinejad, V. and Fathi, R. (2021) Supplementation of granulosa cells conditioned medium with pyruvate and testosterone could improve early follicular development in cultured 1-day-old mouse ovaries. Zygote 29(6), 468475. https://doi.org/10.1017/s0967199421000174.CrossRefGoogle ScholarPubMed
Bailie, E., Maidarti, M., Jack, S., Hawthorn, R., Watson, N., Telfer, E. and Anderson, R.A. (2023) The ovaries of transgender men indicate effects of high dose testosterone on the primordial and early growing follicle pool. Reproduction Fertility 4(2), e220102. https://doi.org/10.1530/raf-22-0102.CrossRefGoogle ScholarPubMed
Bhardwaj, J.K., Paliwal, A., Saraf, P. and Sachdeva, S.N. (2022) Role of autophagy in follicular development and maintenance of primordial follicular pool in the ovary. Journal of Cellular Physiology 237(2), 11571170. https://doi.org/10.1002/jcp.30613.CrossRefGoogle ScholarPubMed
Bockstaele, L., Tsepelidis, S., Dechene, J., Englert, Y. and Demeestere, I. (2012) Safety of ovarian tissue autotransplantation for cancer patients. Obstetrics and Gynecology International 2012, 495142. https://doi.org/10.1155/2012/495142.CrossRefGoogle ScholarPubMed
Casarini, L. and Crépieux, P. (2019) Molecular mechanisms of action of FSH. Frontiers in Endocrinology 10, 305. https://doi.org/10.3389/fendo.2019.00305.CrossRefGoogle ScholarPubMed
Chen, X.-Y., Xia, H.-X., Guan, H.-Y., Li, B. and Zhang, W. (2016) Follicle loss and apoptosis in cyclophosphamide-treated mice: what’s the matter? International Journal of Molecular Sciences 17(6), 836.CrossRefGoogle ScholarPubMed
Chen, Y., Yang, W., Shi, X., Zhang, C., Song, G. and Huang, D. (2020) The Factors and Pathways Regulating the Activation of Mammalian Primordial Follicles in vivo. Frontiers in Cell and Developmental Biology 8, 575706. https://doi.org/10.3389/fcell.2020.575706.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. https://doi.org/10.1095/biolreprod54.1.197.CrossRefGoogle ScholarPubMed
Fan, X., Bialecka, M., Moustakas, I., Lam, E., Torrens-Juaneda, V., Borggreven, N.V., Trouw, L., Louwe, L.A., Pilgram, G.S.K., Mei, H., van der Westerlaken, L. and Chuva de Sousa Lopes, S.M. (2019) Single-cell reconstruction of follicular remodeling in the human adult ovary. Nature Communications 10(1), 3164. https://doi.org/10.1038/s41467-019-11036-9.CrossRefGoogle ScholarPubMed
Fathi, R., Rezazadeh Valojerdi, M., Ebrahimi, B., Eivazkhani, F., Akbarpour, M., Tahaei, L.S. and Abtahi, N.S. (2017) Fertility preservation in cancer patients: in vivo and in vitro options. Cell Journal (Yakhteh) 19(2), 173183. https://doi.org/10.22074/cellj.2016.4880.Google ScholarPubMed
Findlay, J.K., Hutt, K.J., Hickey, M. and Anderson, R.A. (2015) How is the number of primordial follicles in the ovarian reserve established? Biology of Reproduction 93(5), 111. https://doi.org/10.1095/biolreprod.115.133652.CrossRefGoogle Scholar
Firestone, G.L. and Kapadia, B.J. (2012) Minireview: regulation of gap junction dynamics by nuclear hormone receptors and their ligands. Molecular Endocrinology 26(11), 17981807. https://doi.org/10.1210/me.2012-1065.CrossRefGoogle ScholarPubMed
Ford, E.A., Beckett, E.L., Roman, S.D., McLaughlin, E.A. and Sutherland, J.M. (2020) Advances in human primordial follicle activation and premature ovarian insufficiency. Reproduction 159(1), R15r29. https://doi.org/10.1530/rep-19-0201.CrossRefGoogle Scholar
Fujibe, Y., Baba, T., Nagao, S., Adachi, S., Ikeda, K., Morishita, M., Kuno, Y., Suzuki, M., Mizuuchi, M., Honnma, H., Endo, T. and Saito, T. (2019) Androgen potentiates the expression of FSH receptor and supports preantral follicle development in mice. Journal of Ovarian Research 12(1), 31. https://doi.org/10.1186/s13048-019-0505-5.CrossRefGoogle ScholarPubMed
Gilchrist, R.B., Lane, M. and Thompson, J.G. (2008) Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Human Reproduction Update 14(2), 159177. https://doi.org/10.1093/humupd/dmm040.CrossRefGoogle ScholarPubMed
Griswold, M.D., Kim, J.S. and Tribley, W.A. (2001) Mechanisms involved in the homologous down-regulation of transcription of the follicle-stimulating hormone receptor gene in Sertoli cells. Molecular and Cellular Endocrinology 173(1-2), 95107. https://doi.org/10.1016/s0303-7207(00)00412-3.CrossRefGoogle ScholarPubMed
Hreinsson, J.G., Scott, J.E., Rasmussen, C., Swahn, M.L., Hsueh, A.J. and Hovatta, O. (2002) Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture. The Journal of Clinical Endocrinology and Metabolism 87(1), 316321. https://doi.org/10.1210/jcem.87.1.8185.CrossRefGoogle ScholarPubMed
Hussein, M.R. (2005) Apoptosis in the ovary: molecular mechanisms. Human Reproduction Update 11(2), 162178.CrossRefGoogle ScholarPubMed
Jeruss, J.S. and Woodruff, T.K. (2009) Preservation of fertility in patients with cancer. New England Journal of Medicine 360(9), 902911. https://doi.org/10.1056/NEJMra0801454.CrossRefGoogle ScholarPubMed
Jewgenow, K. and Paris, M.C. (2006) Preservation of female germ cells from ovaries of cat species. Theriogenology 66(1), 93100. https://doi.org/10.1016/j.theriogenology.2006.03.010.CrossRefGoogle ScholarPubMed
Juneja, S.C., Barr, K.J., Enders, G.C. and Kidder, G.M. (1999) Defects in the germ line and gonads of mice lacking connexin43. Biology of Reproduction 60(5), 12631270. https://doi.org/10.1095/biolreprod60.5.1263.CrossRefGoogle ScholarPubMed
Kedem, A., Fisch, B., Garor, R., Ben-Zaken, A., Gizunterman, T., Felz, C., Ben-Haroush, A., Kravarusic, D. and Abir, R. (2011) Growth differentiating factor 9 (GDF9) and bone morphogenetic protein 15 both activate development of human primordial follicles in vitro, with seemingly more beneficial effects of GDF9. The Journal of Clinical Endocrinology and Metabolism 96(8), E12461254. https://doi.org/10.1210/jc.2011-0410.CrossRefGoogle ScholarPubMed
Kerr, J.B., Duckett, R., Myers, M., Britt, K.L., Mladenovska, T. and Findlay, J.K. (2006) Quantification of healthy follicles in the neonatal and adult mouse ovary: evidence for maintenance of primordial follicle supply. Reproduction 132(1), 95109. https://doi.org/10.1530/rep.1.01128.CrossRefGoogle ScholarPubMed
Khajedehi, N., Fathi, R., Akbarinejad, V. and Gourabi, H. (2024) Oocyte vitrification reduces its capability to repair sperm DNA fragmentation and impairs embryonic development. Reproductive Sciences 31(5),12561267. https://doi.org/10.1007/s43032-023-01419-1.CrossRefGoogle ScholarPubMed
Khodadi, M., Atrabi, M.J., Torkzadeh, T., Fazli, M., Akbarinejad, V. and Fathi, R. (2022) High steroid content in conditioned medium of granulosa cells may disrupt primordial follicles formation in in vitro cultured one-day-old murine ovaries. Reproductive Biology 22(1), 100613. https://doi.org/10.1016/j.repbio.2022.100613.CrossRefGoogle ScholarPubMed
Kim, S.Y. and Kurita, T. (2018) New insights into the role of phosphoinositide 3-Kinase activity in the physiology of immature oocytes: lessons from recent mouse model studies. European Medical Journal Reproductive Health 3(2), 119125.Google ScholarPubMed
Kranc, W., Brązert, M., Budna, J., Celichowski, P., Bryja, A., Nawrocki, M.J., Ożegowska, K., Jankowski, M., Chermuła, B., Dyszkiewicz-Konwińska, M., Jeseta, M., Pawelczyk, L., Bręborowicz, A., Rachoń, D., Bruska, M., Nowicki, M., Zabel, M. and Kempisty, B. (2019) Genes responsible for proliferation, differentiation, and junction adhesion are significantly up-regulated in human ovarian granulosa cells during a long-term primary in vitro culture. Histochemistry and Cell Biology 151(2), 125143. https://doi.org/10.1007/s00418-018-1750-1.CrossRefGoogle Scholar
Laird, M., Thomson, K., Fenwick, M., Mora, J., Franks, S. and Hardy, K. (2017) Androgen stimulates growth of mouse preantral follicles in vitro: interaction with follicle-stimulating hormone and with growth factors of the TGFβ superfamily. Endocrinology 158(4), 920935. https://doi.org/10.1210/en.2016-1538.CrossRefGoogle ScholarPubMed
Li, D., Wang, Q., Shi, K., Lu, Y., Yu, D., Shi, X., Du, W. and Yu, M. (2020) Testosterone promotes the proliferation of chicken embryonic myoblasts via androgen receptor mediated PI3K/Akt signaling pathway. International Journal of Molecular Sciences 21(3), 1152. https://doi.org/10.3390/ijms21031152.CrossRefGoogle ScholarPubMed
Li, L., Shi, X., Shi, Y. and Wang, Z. (2021a) The signaling pathways involved in ovarian follicle development. Frontiers in Physiology 12, 730196. https://doi.org/10.3389/fphys.2021.730196.CrossRefGoogle ScholarPubMed
Li, Y., Li, S., Zhang, Y., Shi, S., Qin, S., Wang, C., Du, J., Ma, J., Chen, H. and Cui, H. (2021b) Androgen plays a carcinogenic role in EOC via the PI3K/AKT signaling pathway in an AR-dependent manner. Journal of Cancer 12(6), 18151825. https://doi.org/10.7150/jca.51099.CrossRefGoogle Scholar
Luyckx, V., Scalercio, S., Jadoul, P., Amorim, C.A., Soares, M., Donnez, J. and Dolmans, M.M. (2013) Evaluation of cryopreserved ovarian tissue from prepubertal patients after long-term xenografting and exogenous stimulation. Fertility and Sterility 100(5), 13501357. https://doi.org/10.1016/j.fertnstert.2013.07.202.CrossRefGoogle ScholarPubMed
Magamage, M.P.S., Zengyo, M., Moniruzzaman, M. and Miyano, T. (2011) Testosterone induces activation of porcine primordial follicles in vitro. Reproductive Medicine and Biology 10(1), 2130. https://doi.org/10.1007/s12522-010-0068-z.CrossRefGoogle ScholarPubMed
Makker, A., Goel, M.M. and Mahdi, A.A. (2014) PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: an update. Journal of Molecular Endocrinology 53(3), R103118. https://doi.org/10.1530/jme-14-0220.CrossRefGoogle ScholarPubMed
Morohaku, K., Tanimoto, R., Sasaki, K., Kawahara-Miki, R., Kono, T., Hayashi, K., Hirao, Y. and Obata, Y. (2016) Complete in vitro generation of fertile oocytes from mouse primordial germ cells. Proceedings of the National Academy of Sciences of the United States of America 113(32), 90219026. https://doi.org/10.1073/pnas.1603817113.CrossRefGoogle ScholarPubMed
Mukherjee, A., Reisdorph, N., Guda, C., Pandey, S. and Roy, S.K. (2012) Changes in ovarian protein expression during primordial follicle formation in the hamster. Molecular and Cellular Endocrinology 348(1), 8794. https://doi.org/10.1016/j.mce.2011.07.043.CrossRefGoogle ScholarPubMed
Nagashima, J.B., Wildt, D.E., Travis, A.J. and Songsasen, N. (2019) Activin promotes growth and antral cavity expansion in the dog ovarian follicle. Theriogenology 129, 168177. https://doi.org/10.1016/j.theriogenology.2019.02.018.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. https://doi.org/10.1095/biolreprod.102.013029.CrossRefGoogle ScholarPubMed
Otsuka, F., McTavish, K.J. and Shimasaki, S. (2011) Integral role of GDF-9 and BMP-15 in ovarian function. Molecular Reproduction and Development 78(1), 921. https://doi.org/10.1002/mrd.21265.CrossRefGoogle ScholarPubMed
Pagotto, A., Pilotto, G., Mazzoldi, E.L., Nicoletto, M.O., Frezzini, S., Pastò, A. and Amadori, A. (2017) Autophagy inhibition reduces chemoresistance and tumorigenic potential of human ovarian cancer stem cells. Cell Death & Disease 8(7), e2943e2943. https://doi.org/10.1038/cddis.2017.327.CrossRefGoogle ScholarPubMed
Pepling, M.E. (2006) From primordial germ cell to primordial follicle: mammalian female germ cell development. Genesis 44(12), 622632. https://doi.org/10.1002/dvg.20258.CrossRefGoogle ScholarPubMed
Persani, L., Rossetti, R., Di Pasquale, E., Cacciatore, C. and Fabre, S. (2014) The fundamental role of bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders. Human Reproduction Update 20(6), 869883. https://doi.org/10.1093/humupd/dmu036.CrossRefGoogle ScholarPubMed
Qureshi, A.I., Nussey, S.S., Bano, G., Musonda, P., Whitehead, S.A. and Mason, H.D. (2008) Testosterone selectively increases primary follicles in ovarian cortex grafted onto embryonic chick membranes: relevance to polycystic ovaries. Reproduction 136(2), 187194. https://doi.org/10.1530/rep-07-0172.CrossRefGoogle ScholarPubMed
Santiquet, N., Robert, C. and Richard, F.J. (2013) The dynamics of connexin expression, degradation and localisation are regulated by gonadotropins during the early stages of in vitro maturation of swine oocytes. PLoS One 8(7), e68456. https://doi.org/10.1371/journal.pone.0068456.CrossRefGoogle ScholarPubMed
Sarma, U.C., Findlay, J.K. and Hutt, K.J. (2019) Oocytes from stem cells. Best Practice and Research. Clinical Obstetrics Gynaecology 55, 1422. https://doi.org/10.1016/j.bpobgyn.2018.07.006.CrossRefGoogle ScholarPubMed
Sen, A., Prizant, H., Light, A., Biswas, A., Hayes, E., Lee, H.J., Barad, D., Gleicher, N. and Hammes, S.R. (2014) Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and microRNA-125b expression. Proceedings of the National Academy of Sciences of the United States of America 111(8), 30083013. https://doi.org/10.1073/pnas.1318978111.CrossRefGoogle ScholarPubMed
Shen, M., Liu, Z., Li, B., Teng, Y., Zhang, J., Tang, Y., Sun, S.C. and Liu, H. (2014) Involvement of FoxO1 in the effects of follicle-stimulating hormone on inhibition of apoptosis in mouse granulosa cells. Cell Death & Disease 5(10), e1475. https://doi.org/10.1038/cddis.2014.400.CrossRefGoogle ScholarPubMed
Shi, X.Y., Guan, Z.Q., Yu, J.N. and Liu, H.L. (2020) Follicle stimulating hormone inhibits the expression of p53 Up-regulated modulator of apoptosis induced by reactive oxygen species through PI3K/Akt in mouse granulosa cells. Physiological Research 69(4), 687694. https://doi.org/10.33549/physiolres.934421.CrossRefGoogle ScholarPubMed
Simon, A.M., Chen, H. and Jackson, C.L. (2006) Cx37 and Cx43 localize to zona pellucida in mouse ovarian follicles. Cell Communication Adhesion 13(1-2), 6177. https://doi.org/10.1080/15419060600631748.CrossRefGoogle ScholarPubMed
Simon, A.M., Goodenough, D.A., Li, E. and Paul, D.L. (1997) Female infertility in mice lacking connexin 37. Nature 385(6616), 525529. https://doi.org/10.1038/385525a0.CrossRefGoogle ScholarPubMed
Simoni, M., Gromoll, J. and Nieschlag, E. (1997) The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocrine Reviews 18(6), 739773. https://doi.org/10.1210/edrv.18.6.0320.Google ScholarPubMed
Teilmann, S.C. (2005) Differential expression and localisation of connexin-37 and connexin-43 in follicles of different stages in the 4-week-old mouse ovary. Molecular and Cellular Endocrinology 234(1-2), 2735. https://doi.org/10.1016/j.mce.2004.10.014.CrossRefGoogle ScholarPubMed
Telfer, E.E., McLaughlin, M., Ding, C. and Thong, K.J. (2008) A two-step serum-free culture system supports development of human oocytes from primordial follicles in the presence of activin. Human Reproduction (Oxford, England) 23(5), 11511158. https://doi.org/10.1093/humrep/den070.CrossRefGoogle ScholarPubMed
Telfer, E.E. and Zelinski, M.B. (2013) Ovarian follicle culture: advances and challenges for human and nonhuman primates. Fertility and Sterility 99(6), 15231533. https://doi.org/10.1016/j.fertnstert.2013.03.043.CrossRefGoogle ScholarPubMed
Tingen, C.M., Bristol-Gould, S.K., Kiesewetter, S.E., Wellington, J.T., Shea, L. and Woodruff, T.K. (2009) Prepubertal primordial follicle loss in mice is not due to classical apoptotic pathways. Biology of Reproduction 81(1), 1625.CrossRefGoogle Scholar
Torkzadeh, T., Asadi, Z., Jafari Atrabi, M., Eivazkhani, F., Khodadi, M., Hajiaghalou, S., Akbarinejad, V. and Fathi, R. (2023) Optimisation of hormonal treatment to improve follicular development in one-day-old mice ovaries cultured under in vitro condition. Reproduction Fertility and Development 35(18), 733749. https://doi.org/10.1071/rd23027.CrossRefGoogle ScholarPubMed
Vitt, U.A., McGee, E.A., Hayashi, M. and Hsueh, A.J. (2000) In vivo treatment with GDF-9 stimulates primordial and primary follicle progression and theca cell marker CYP17 in ovaries of immature rats. Endocrinology 141(10), 38143820. https://doi.org/10.1210/endo.141.10.7732.CrossRefGoogle ScholarPubMed
White, J.P., Gao, S., Puppa, M.J., Sato, S., Welle, S.L. and Carson, J.A. (2013) Testosterone regulation of Akt/mTORC1/FoxO3a signaling in skeletal muscle. Molecular and Cellular Endocrinology 365(2), 174186. https://doi.org/10.1016/j.mce.2012.10.019.CrossRefGoogle ScholarPubMed
Yoo, M., Tanaka, T., Konishi, H., Tanabe, A., Taniguchi, K., Komura, K., Hayashi, M. and Ohmichi, M. (2020) The protective effect of testosterone on the ovarian reserve during cyclophosphamide treatment. OncoTargets and therapy 13, 29872995. https://doi.org/10.2147/ott.S242703.CrossRefGoogle ScholarPubMed
Zhang, T., He, M., Zhang, J., Tong, Y., Chen, T., Wang, C., Pan, W. and Xiao, Z. (2023) Mechanisms of primordial follicle activation and new pregnancy opportunity for premature ovarian failure patients. Frontiers in Physiology 14, 1113684. https://doi.org/10.3389/fphys.2023.1113684.CrossRefGoogle ScholarPubMed
Zhao, J., Liu, G.L., Wei, Y., Jiang, L.H., Bao, P.L. and Yang, Q.Y. (2016) Low-dose testosterone alleviates vascular damage caused by castration in male rats in puberty via modulation of the PI3K/AKT signaling pathway. Molecular Medicine Reports 14(3), 25182526. https://doi.org/10.3892/mmr.2016.5562.CrossRefGoogle ScholarPubMed
Zhao, Y., Feng, H., Zhang, Y., Zhang, J.V., Wang, X., Liu, D., Wang, T., Li, R.H.W., Ng, E.H.Y., Yeung, W.S.B., Rodriguez-Wallberg, K.A. and Liu, K. (2021) Current understandings of core pathways for the activation of mammalian primordial follicles. Cells 10(6), 1491. https://doi.org/10.3390/cells10061491.CrossRefGoogle ScholarPubMed
Zhou, J., Peng, X. and Mei, S. (2019) Autophagy in ovarian follicular development and atresia. International Journal of Biological Sciences 15(4), 726737. https://doi.org/10.7150/ijbs.30369.CrossRefGoogle ScholarPubMed