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Prenatal and pubertal exposure to 17α-ethinylestradiol disrupts folliculogenesis and promotes morphophysiological changes in ovaries of old gerbils (Meriones unguiculatus)

Published online by Cambridge University Press:  02 March 2021

Vinícius Gonçalves de Souza ,
Laura Borges Bandeira ,
Nátaly Caroline Silva e Souza ,
Sebastião Roberto Taboga ,
Tracy Martina Marques Martins  and
Ana Paula Silva Perez Open the ORCID record for Ana Paula Silva Perez [Opens in a new window]
Vinícius Gonçalves de Souza
Affiliation:
Institute of Health Sciences, Medicine Course, Federal University of Jataí, UFJ, Jataí, Goiás 75801-615, Brazil
Laura Borges Bandeira
Affiliation:
Institute of Health Sciences, Medicine Course, Federal University of Jataí, UFJ, Jataí, Goiás 75801-615, Brazil
Nátaly Caroline Silva e Souza
Affiliation:
Institute of Health Sciences, Medicine Course, Federal University of Jataí, UFJ, Jataí, Goiás 75801-615, Brazil
Sebastião Roberto Taboga
Affiliation:
Department of Biology, Laboratory of Microscopy and Microanalysis, São Paulo State University – UNESP, São José do Rio Preto, São Paulo 15054-000, Brazil Department of Structural and Functional Biology, State University of Campinas – UNICAMP, Campinas, São Paulo 13083-970, Brazil
Tracy Martina Marques Martins
Affiliation:
Institute of Health Sciences, Medicine Course, Federal University of Jataí, UFJ, Jataí, Goiás 75801-615, Brazil
Ana Paula Silva Perez*
Affiliation:
Institute of Health Sciences, Medicine Course and Graduate Program of Animal Bioscience, Federal University of Jataí, UFJ, Jataí, Goiás 75801-615, Brazil
*
Address for correspondence: Dr. Ana Paula Silva Perez, Institute of Health Sciences, Medicine Course – Federal University of Goiás – UFG, Jataí, Goiás, BR 364, Km 194, number 3800, Class of Teachers II, number 26, Jatobá campus – University City, Jataí, GO, Brazil. Email: [email protected]
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Abstract

17α-Ethinylestradiol is an endocrine-disrupting chemical that make up most contraceptive pills and can be found in the environment. Exposure to ethinylestradiol in different development periods may promote changes in morphophysiological parameters of reproductive and endocrine organs. Considering that the effects of low doses (15 µg/kg/day) of ethinylestradiol in ovaries from 12-month-old female gerbils (Meriones unguiculatus) were investigated. Four experimental groups used were control (without treatment), EE/PRE (treated from the 18th to the 22nd gestational day), EE/PUB (treated from the 42nd to the 49th day of life), and EE/PRE-PUB (treated in the both periods). The animals were euthanized at 12 months. Testosterone and 17β-estradiol levels were measured. The ovaries were stained with Hematoxylin and Eosin, Periodic Acid Schiff, and Gomori’s Trichome. The follicles, corpus luteum, interstitial gland, lipofuscin, ovarian epithelium, and tunica albuginea were analyzed. Estradiol was higher in EE/PRE and EE/PUB groups, while testosterone was higher only in EE/PUB group. The main changes in follicle count occurred in EE/PUB and EE/PRE-PUB groups, with higher primordial follicle count and lower maturation of follicles. The corpus luteum was more evident in EE/PRE group. No differences were found in atretic follicles count. A higher area occupied by interstitial gland cells and lipofuscin deposit in these cells was noted in EE/PUB and EE/PRE-PUB groups. Higher epithelium height and thicker tunic albuginea were showed in treated groups. These results suggest that exposure to doses of EE2 in prenatal and pubertal periods of the development leads to morphological changes in senile ovaries.

Keywords

Gerbillinaeovarycontraceptive agentsendocrine disruptors
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 13 , Issue 1 , February 2022 , pp. 49 - 60
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Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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References

Fowler, PA, Bellingham, M, Sinclair, KD, et al. Impact of endocrine-disrupting compounds (EDCs) on female reproductive health. Mol Cell Endocrinol. 2012; 355(2), 231–239. doi: 10.1016/j.mce.2011.10.021 CrossRefGoogle ScholarPubMed
Frye, CA, Bo, E, Calamandrei, G, et al. Endocrine disrupters: a review of some sources, effects, and mechanisms of actions on behaviour and neuroendocrine systems. J Neuroendocrinol. 2012; 24(1), 144–159. doi: 10.1111/j.1365-2826.2011.02229.x CrossRefGoogle ScholarPubMed
Nozawa, K, Nagaoka, K, Zhang, H, et al. Neonatal exposure to 17α-ethynyl estradiol affects ovarian gene expression and disrupts reproductive cycles in female rats. Reprod Toxicol. 2014; 46, 77–84. doi: 10.1016/j.reprotox.2014.03.001 CrossRefGoogle ScholarPubMed
Ryan, BC, Hotchkiss, AK, Crofton, KM, Gray, LEJ. In utero and lactational exposure to bisphenol A, in contrast to ethinyl estradiol, does not alter sexually dimorphic behavior, puberty, fertility, and anatomy of female LE rats. Toxicol Sci. 2010; 114(1), 133–148. doi: 10.1093/toxsci/kfp266 CrossRefGoogle Scholar
Kezele, P, Skinner, MK. Regulation of ovarian primordial follicle assembly and development by estrogen and progesterone: endocrine model of follicle assembly. Endocrinology. 2003; 144(8), 3329–3337. doi: 10.1210/en.2002-0131 CrossRefGoogle ScholarPubMed
Drummond, AE, Fuller, PJ. Ovarian actions of estrogen receptor-β: an update. Semin Reprod Med. 2012; 30(1), 32–38. doi: 10.1055/s-0031-1299595 Google ScholarPubMed
Zhang, H, Nagaoka, K, Usuda, K, et al. Estrogenic compounds impair primordial follicle formation by inhibiting the expression of Proapoptotic Hrk in neonatal rat ovary. Biol Reprod. 2016; 95(4), 78. doi: 10.1095/biolreprod.116.141309 CrossRefGoogle ScholarPubMed
Zhang, H, Taya, K, Nagaoka, K, Yoshida, M, Watanabe, G. Neonatal exposure to 17α-ethynyl estradiol (EE) disrupts follicle development and reproductive hormone profiles in female rats. Toxicol Lett. 2017; 276, 92–99. doi: 10.1016/j.toxlet.2017.05.014 CrossRefGoogle ScholarPubMed
Zhang, J, Chen, Q, Du, D, et al. Can ovarian aging be delayed by pharmacological strategies? Aging (Albany NY). 2019; 11(2), 817–832. doi: 10.18632/aging.101784 CrossRefGoogle ScholarPubMed
Vincent, AL, Rodrick, GE, Sodeman, WA. The Mongolian gerbil in aging research. Exp Aging Res. 1980; 6(3), 249–260. doi: 10.1080/03610738008258361 CrossRefGoogle ScholarPubMed
Perez, APS, Biancardi, MF, Caires, CRS, et al. Prenatal exposure to ethinylestradiol alters the morphologic patterns and increases the predisposition for prostatic lesions in male and female gerbils during ageing. Int J Exp Pathol. 2016; 97(1), 5–17. doi: 10.1111/iep.12153 CrossRefGoogle ScholarPubMed
Perez, APS, Biancardi, MF, Caires, CRS, et al. Pubertal exposure to ethinylestradiol promotes different effects on the morphology of the prostate of the male and female gerbil during aging. Environ Toxicol. 2017; 32(2), 477–489. doi: 10.1002/tox.22252 CrossRefGoogle ScholarPubMed
Lv, X, Shi, D. Combined effects of levonorgestrel and quinestrol on reproductive hormone levels and receptor expression in females of the Mongolian gerbil (Meriones unguiculatus). Zoolog Sci. 2012; 29(1), 37–42. doi: 10.2108/zsj.29.37 CrossRefGoogle Scholar
Su, Q-Q, Chen, Y, Qin, J, Wang, T-L, Wang, D-H, Liu, Q-S. Responses in reproductive organs, steroid hormones and CYP450 enzymes in female Mongolian gerbil (Meriones unguiculatus) over time after quinestrol treatment. Pestic Biochem Physiol. 2017; 143, 122–126. doi: 10.1016/j.pestbp.2017.08.008 CrossRefGoogle ScholarPubMed
Thayer, KA, Ruhlen, RL, Howdeshell, KL, et al. Altered prostate growth and daily sperm production in male mice exposed prenatally to subclinical doses of 17alpha-ethinyl oestradiol. Hum Reprod. 2001; 16(5), 988–996. doi: 10.1093/humrep/16.5.988 CrossRefGoogle ScholarPubMed
Pinto-Fochi, ME, Negrin, AC, Scarano, WR, Taboga, SR, Góes, RM. Sexual maturation of the Mongolian gerbil (Meriones unguiculatus): a histological, hormonal and spermatic evaluation. Reprod Fertil Dev. 2016; 28(6), 815–823. doi: 10.1071/RD14074 CrossRefGoogle ScholarPubMed
Siegford, JM, Hadi Mansouri, S, Ulibarri, C. Normal ontogeny of perineal muscles and testosterone levels in Mongolian gerbils; response to testosterone in developing females. Anat Rec Part A, Discov Mol Cell Evol Biol. 2003; 275(1), 997–1008. doi: 10.1002/ar.a.10118 CrossRefGoogle ScholarPubMed
Santos, FCA, Falleiros-Júnior, LR, Corradi, LS, Vilamaior, PSL, Taboga, SR. Experimental endocrine therapies promote epithelial cytodifferentiation and ciliogenesis in the gerbil female prostate. Cell Tissue Res. 2007; 328(3), 617–624. doi: 10.1007/s00441-007-0381-y CrossRefGoogle ScholarPubMed
Scarano, WR, de Sousa, DE, Campos, SGP, Corradi, LS, Vilamaior, PSL, Taboga, SR. Oestrogen supplementation following castration promotes stromal remodelling and histopathological alterations in the Mongolian gerbil ventral prostate. Int J Exp Pathol. 2008; 89(1), 25–37. doi: 10.1111/j.1365-2613.2007.00559.x CrossRefGoogle ScholarPubMed
Scarano, WR, Vilamaior, PSL, Taboga, SR. Tissue evidence of the testosterone role on the abnormal growth and aging effects reversion in the gerbil (Meriones unguiculatus) prostate. Anat Rec Part A, Discov Mol Cell Evol Biol. 2006; 288(11), 1190–1200. doi: 10.1002/ar.a.20391 CrossRefGoogle ScholarPubMed
Nishino, N, Totsukawa, K. Study on the estrous cycle in the Mongolian gerbil (Meriones unguiculatus). Exp Anim. 1996; 45(3), 283–288. doi: 10.1538/expanim.45.283 CrossRefGoogle Scholar
Fochi, RA, Perez, APS, Bianchi, C V, et al. Hormonal oscillations during the estrous cycle influence the morphophysiology of the gerbil (Meriones unguiculatus) female prostate (skene paraurethral glands). Biol Reprod. 2008; 79(6), 1084–1091. doi: 10.1095/biolreprod.108.070540 CrossRefGoogle Scholar
Feldman, AT, Wolfe, D. Tissue processing and hematoxylin and eosin staining. Methods Mol Biol. 2014; 1180, 31–43. doi: 10.1007/978-1-4939-1050-2_3 CrossRefGoogle ScholarPubMed
Kligman, AM, Mescon, H. The periodic acid-Schiff stain for the demonstration of fungi in animal tissue. J Bacteriol. 1950; 60(4), 415–421.CrossRefGoogle ScholarPubMed
Gomori, G. A rapid one-step trichrome stain. Am J Clin Pathol. 1950; 20(7), 661–664. doi: 10.1093/ajcp/20.7_ts.661 CrossRefGoogle ScholarPubMed
Luo, LL, Huang, J, Fu, YC, Xu, JJ, Qian, YS. Effects of tea polyphenols on ovarian development in rats. J Endocrinol Invest. 2008; 31(12), 1110–1118. doi: 10.1007/BF03345661 CrossRefGoogle ScholarPubMed
Takagi, K, Yamada, T, Miki, Y, Umegaki, T, Nishimura, M, Sasaki, J. Histological observation of the development of follicles and follicular atresia in immature rat ovaries. Acta Med Okayama. 2007; 61(5), 283–298. doi: 10.18926/AMO/32892 Google ScholarPubMed
Saidapur, SK, Kamath, SR. Morphometric study of ovarian follicular growth during the estrous cycle of the laboratory-maintained Indian desert gerbil, Meriones hurrianae (Jerdon). Acta Anat (Basel). 1993; 148(4), 189–196. doi: 10.1159/000147540 CrossRefGoogle Scholar
Wang, W, Liu, H-L, Tian, W, et al. Morphologic observation and classification criteria of atretic follicles in guinea pigs. J Zhejiang Univ Sci B. 2010; 11(5), 307–314. doi: 10.1631/jzus.B0900391 CrossRefGoogle ScholarPubMed
Weibel, ER. Principles and methods for the morphometric study of the lung and other organs. Lab Invest. 1963; 12, 131–155.Google ScholarPubMed
Díaz-Hernández, V, Caldelas, I, Montaño, LM, Merchant-Larios, H. Morphological rearrangement of the cortical region, in aging ovaries. Histol Histopathol. 2019; 34(7), 775–789. doi: 10.14670/HH-18-078 Google ScholarPubMed
Angelousi, A, Szarek, E, Shram, V, Kebebew, E, Quezado, M, Stratakis, CA. Lipofuscin accumulation in Cortisol-producing adenomas with and without PRKACA mutations. Horm Metab Res = Horm und Stoffwechselforsch = Horm Metab. 2017; 49(10), 786–792. doi: 10.1055/s-0043-116385 Google ScholarPubMed
Lunde, O, Hoel, PS, Sandvik, L. Ovarian morphology in patients with polycystic ovaries and in an age-matched reference material. A statistical evaluation of 149 cases. Gynecol Obstet Invest. 1988; 25(3), 192–201. doi: 10.1159/000293771 CrossRefGoogle Scholar
Atkins, HM, Willson, CJ, Silverstein, M, et al. Characterization of ovarian aging and reproductive senescence in vervet monkeys (Chlorocebus aethiops sabaeus). Comp Med. 2014; 64(1), 55–62.Google Scholar
Nichols, SM, Bavister, BD, Brenner, CA, Didier, PJ, Harrison, RM, Kubisch, HM. Ovarian senescence in the rhesus monkey (Macaca mulatta). Hum Reprod. 2005; 20(1), 79–83. doi: 10.1093/humrep/deh576 CrossRefGoogle Scholar
Xi, W, Lee, CKF, Yeung, WSB, et al. Effect of perinatal and postnatal bisphenol A exposure to the regulatory circuits at the hypothalamus-pituitary-gonadal axis of CD-1 mice. Reprod Toxicol. 2011; 31(4), 409–417. doi: 10.1016/j.reprotox.2010.12.002 CrossRefGoogle Scholar
Brehm, E, Rattan, S, Gao, L, Flaws, JA. Prenatal exposure to Di(2-Ethylhexyl) phthalate causes long-term transgenerational effects on female reproduction in mice. Endocrinology. 2018; 159(2), 795–809. doi: 10.1210/en.2017-03004 CrossRefGoogle ScholarPubMed
Zha, J, Sun, L, Zhou, Y, Spear, PA, Ma, M, Wang, Z. Assessment of 17alpha-ethinylestradiol effects and underlying mechanisms in a continuous, multigeneration exposure of the Chinese rare minnow (Gobiocypris rarus). Toxicol Appl Pharmacol. 2008; 226(3), 298–308. doi: 10.1016/j.taap.2007.10.006 CrossRefGoogle Scholar
Dávila-Esqueda, ME, Jiménez-Capdeville, ME, Delgado, JM, et al. Effects of arsenic exposure during the pre- and postnatal development on the puberty of female offspring. Exp Toxicol Pathol Off J Gesellschaft fur Toxikologische Pathol. 2012; 64(1–2), 25–30. doi: 10.1016/j.etp.2010.06.001 CrossRefGoogle ScholarPubMed
Lite, C, Ahmed, SSSJ, Santosh, W, Seetharaman, B. Prenatal exposure to bisphenol-A altered miRNA-224 and protein expression of aromatase in ovarian granulosa cells concomitant with elevated serum estradiol levels in F(1) adult offspring. J Biochem Mol Toxicol. 2019; 33(6), e22317. doi: 10.1002/jbt.22317 CrossRefGoogle Scholar
Eppig, JJ, Pendola, FL, Wigglesworth, K, Pendola, JK. Mouse oocytes regulate metabolic cooperativity between granulosa cells and oocytes: amino acid transport. Biol Reprod. 2005; 73(2), 351–357. doi: 10.1095/biolreprod.105.041798 CrossRefGoogle ScholarPubMed
Bendell, JJ, Dorrington, J. Estradiol-17 beta stimulates DNA synthesis in rat granulosa cells: action mediated by transforming growth factor-beta. Endocrinology. 1991; 128(5), 2663–2665. doi: 10.1210/endo-128-5-2663 CrossRefGoogle ScholarPubMed
Dupont, S, Krust, A, Gansmuller, A, Dierich, A, Chambon, P, Mark, M. Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes. Development. 2000; 127(19), 4277–4291.CrossRefGoogle ScholarPubMed
Emmen, JMA, Couse, JF, Elmore, SA, Yates, MM, Kissling, GE, Korach, KS. In vitro growth and ovulation of follicles from ovaries of estrogen receptor (ER){alpha} and ER{beta} null mice indicate a role for ER{beta} in follicular maturation. Endocrinology. 2005; 146(6), 2817–2826. doi: 10.1210/en.2004-1108 CrossRefGoogle ScholarPubMed
Tarumi, W, Itoh, MT, Suzuki, N. Effects of 5α-dihydrotestosterone and 17β-estradiol on the mouse ovarian follicle development and oocyte maturation. PLoS One. 2014; 9(6), e99423. doi: 10.1371/journal.pone.0099423 CrossRefGoogle ScholarPubMed
Sotomayor-Zárate, R, Dorfman, M, Paredes, A, Lara, HE. Neonatal exposure to estradiol valerate programs ovarian sympathetic innervation and follicular development in the adult rat. Biol Reprod. 2008; 78(4), 673–680. doi: 10.1095/biolreprod.107.063974 CrossRefGoogle ScholarPubMed
Sawyer, HR, Smith, P, Heath, DA, Juengel, JL, Wakefield, SJ, McNatty, KP. Formation of ovarian follicles during fetal development in sheep. Biol Reprod. 2002; 66(4), 1134–1150. doi: 10.1095/biolreprod66.4.1134 CrossRefGoogle ScholarPubMed
Pepling, ME, Spradling, AC. Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles. Dev Biol. 2001; 234(2), 339–351. doi: 10.1006/dbio.2001.0269 CrossRefGoogle ScholarPubMed
Chen, Y, Jefferson, WN, Newbold, RR, Padilla-Banks, E, Pepling, ME. Estradiol, progesterone, and genistein inhibit oocyte nest breakdown and primordial follicle assembly in the neonatal mouse ovary in vitro and in vivo. Endocrinology. 2007; 148(8), 3580–3590. doi: 10.1210/en.2007-0088 CrossRefGoogle ScholarPubMed
Rodríguez, HA, Santambrosio, N, Santamaría, CG, Muñoz-de-Toro, M, Luque, EH. Neonatal exposure to bisphenol A reduces the pool of primordial follicles in the rat ovary. Reprod Toxicol. 2010; 30(4), 550–557. doi: 10.1016/j.reprotox.2010.07.008 CrossRefGoogle ScholarPubMed
Wang, C, Roy, SK. Development of primordial follicles in the hamster: role of estradiol-17beta. Endocrinology. 2007; 148(4), 1707–1716. doi: 10.1210/en.2006-1193 CrossRefGoogle ScholarPubMed
Karavan, JR, Pepling, ME. Effects of estrogenic compounds on neonatal oocyte development. Reprod Toxicol. 2012; 34(1), 51–56. doi: 10.1016/j.reprotox.2012.02.005 CrossRefGoogle ScholarPubMed
Edson, MA, Nagaraja, AK, Matzuk, MM. The mammalian ovary from genesis to revelation. Endocr Rev. 2009; 30(6), 624–712. doi: 10.1210/er.2009-0012 CrossRefGoogle ScholarPubMed
Patel, S, Brehm, E, Gao, L, Rattan, S, Ziv-Gal, A, Flaws, JA. Bisphenol A exposure, ovarian follicle numbers, and female sex steroid hormone levels: results from a CLARITY-BPA study. Endocrinology. 2017; 158(6), 1727–1738. doi: 10.1210/en.2016-1887 CrossRefGoogle ScholarPubMed
Shirota, M, Kawashima, J, Nakamura, T, Kamiie, J, Shirota, K, Yoshida, M. Dose-dependent acceleration in the delayed effects of neonatal oral exposure to low-dose 17α-ethynylestradiol on reproductive functions in female Sprague-Dawley rats. J Toxicol Sci. 2015; 40(6), 727–738. doi: 10.2131/jts.40.727 CrossRefGoogle ScholarPubMed
Silvia, WJ, Lewis, GS, McCracken, JA, Thatcher, WW, Wilson, LJ. Hormonal regulation of uterine secretion of prostaglandin F2 alpha during luteolysis in ruminants. Biol Reprod. 1991; 45(5), 655–663. doi: 10.1095/biolreprod45.5.655 CrossRefGoogle ScholarPubMed
Fischer, T V, Fisher, DL. Effect of gonadotropins on ovulation and ovarian histology in the immature Mongolian gerbil. Am J Anat. 1975; 142(3), 391–396. doi: 10.1002/aja.1001420308 CrossRefGoogle ScholarPubMed
Meckley, PE, Ginther, OJ. Effects of litter and male on corpora lutea of the postpartum Mongolian gerbil. J Anim Sci. 1972; 34(2), 297–301. doi: 10.2527/jas1972.342297x CrossRefGoogle ScholarPubMed
Kaptaner, B, Unal, G. Effects of 17α-ethynylestradiol and nonylphenol on liver and gonadal apoptosis and histopathology in Chalcalburnus tarichi. Environ Toxicol. 2011; 26(6), 610–622. doi: 10.1002/tox.20585 CrossRefGoogle ScholarPubMed
Sridevi, P, Chaitanya, RK, Prathibha, Y, Balakrishna, SL, Dutta-Gupta, A, Senthilkumaran, B. Early exposure of 17α-ethynylestradiol and diethylstilbestrol induces morphological changes and alters ovarian steroidogenic pathway enzyme gene expression in catfish, Clarias gariepinus. Environ Toxicol. 2015; 30(4), 439–451. doi: 10.1002/tox.21920 CrossRefGoogle ScholarPubMed
Talsness, C, Grote, K, Kuriyama, S, et al. Prenatal exposure to the phytoestrogen daidzein resulted in persistent changes in ovarian surface epithelial cell height, folliculogenesis, and estrus phase length in adult Sprague-Dawley rat offspring. J Toxicol Environ Health A. 2015; 78(10), 635–644. doi: 10.1080/15287394.2015.1006711 CrossRefGoogle Scholar
Limon, NM. U de, médecine. F de. Étude histologique et histogénique de la glande interstitielle de l’ovaire. Published online 1901.Google Scholar
Guraya, SS, Greenwald, GS. A comparative histochemical study of interstitial tissue and follicular atresia in the mammalian ovary. Anat Rec. 1964; 149, 411–433. doi: 10.1002/ar.1091490311 CrossRefGoogle Scholar
Adashi, EY. The climacteric ovary as a functional gonadotropin-driven androgen-producing gland. Fertil Steril. 1994; 62(1), 20–27. doi: 10.1016/s0015-0282(16)56810-1 CrossRefGoogle ScholarPubMed
Erickson, GF, Magoffin, DA, Dyer, CA, Hofeditz, C. The ovarian androgen producing cells: a review of structure/function relationships. Endocr Rev. 1985; 6(3), 371–399. doi: 10.1210/edrv-6-3-371 CrossRefGoogle ScholarPubMed
Brodowski, J, Brodowska, A, Laszczyńska, M, Chlubek, D, Starczewski, A. Hormone concentrations in the homogenates of ovarian tissue and blood serum in postmenopausal women not using hormone therapy. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol. 2012; 28(5), 396–399. doi: 10.3109/09513590.2012.664189 CrossRefGoogle Scholar
Fogle, RH, Stanczyk, FZ, Zhang, X, Paulson, RJ. Ovarian androgen production in postmenopausal women. J Clin Endocrinol Metab. 2007; 92(8), 3040–3043. doi: 10.1210/jc.2007-0581 CrossRefGoogle ScholarPubMed
Havelock, JC, Rainey, WE, Bradshaw, KD, Carr, BR. The post-menopausal ovary displays a unique pattern of steroidogenic enzyme expression. Hum Reprod. 2006; 21(1), 309–317. doi: 10.1093/humrep/dei373 CrossRefGoogle ScholarPubMed
Laszczyńska, M, Brodowska, A, Starczewski, A, Masiuk, M, Brodowski, J. Human postmenopausal ovary—hormonally inactive fibrous connective tissue or more? Histol Histopathol. 2008; 23(2), 219–226. doi: 10.14670/HH-23.219 Google ScholarPubMed
Brinton, LA, Trabert, B, Anderson, GL, et al. Serum estrogens and estrogen metabolites and endometrial cancer risk among postmenopausal women. Cancer Epidemiol biomarkers Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol. 2016; 25(7), 1081–1089. doi: 10.1158/1055-9965.EPI-16-0225 CrossRefGoogle ScholarPubMed
Yue, W, Wang, J-P, Li, Y, et al. Effects of estrogen on breast cancer development: role of estrogen receptor independent mechanisms. Int J Cancer. 2010; 127(8), 1748–1757. doi: 10.1002/ijc.25207 CrossRefGoogle ScholarPubMed
Iorga, A, Cunningham, CM, Moazeni, S, Ruffenach, G, Umar, S, Eghbali, M. The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biol Sex Differ. 2017; 8(1), 33. doi: 10.1186/s13293-017-0152-8 CrossRefGoogle ScholarPubMed
Ramalho-Santos, J, Amaral, S. Mitochondria and mammalian reproduction. Mol Cell Endocrinol. 2013; 379(1–2), 74–84. doi: 10.1016/j.mce.2013.06.005 CrossRefGoogle ScholarPubMed
López-Otín, C, Blasco, MA, Partridge, L, Serrano, M, Kroemer, G. The hallmarks of aging. Cell. 2013; 153(6), 1194–1217. doi: 10.1016/j.cell.2013.05.039 CrossRefGoogle ScholarPubMed
Jung, T, Bader, N, Grune, T. Lipofuscin: formation, distribution, and metabolic consequences. Ann N Y Acad Sci. 2007; 1119, 97–111. doi: 10.1196/annals.1404.008 CrossRefGoogle ScholarPubMed
Urzua, U, Chacon, C, Espinoza, R, Martínez, S, Hernandez, N. Parity-dependent hemosiderin and lipofuscin accumulation in the reproductively aged mouse ovary. Anal Cell Pathol (Amst). 2018; 2018, 1289103. doi: 10.1155/2018/1289103 Google ScholarPubMed
Bernstein, L, Pike, MC, Ross, RK, Judd, HL, Brown, JB, Henderson, BE. Estrogen and sex hormone-binding globulin levels in nulliparous and parous women. J Natl Cancer Inst. 1985; 74(4), 741–745.Google ScholarPubMed
Wu, R, Van der Hoek, KH, Ryan, NK, Norman, RJ, Robker, RL. Macrophage contributions to ovarian function. Hum Reprod Update. 2004; 10(2), 119–133. doi: 10.1093/humupd/dmh011 CrossRefGoogle ScholarPubMed
Murdoch, WJ, Van Kirk, EA. Steroid hormonal regulation of proliferative, p53 tumor suppressor, and apoptotic responses of sheep ovarian surface epithelial cells. Mol Cell Endocrinol. 2002; 186(1), 61–67. doi: 10.1016/s0303-7207(01)00675-x CrossRefGoogle ScholarPubMed
Syed, V, Ulinski, G, Mok, SC, Ho, S-M. Reproductive hormone-induced, STAT3-mediated interleukin 6 action in normal and malignant human ovarian surface epithelial cells. J Natl Cancer Inst. 2002; 94(8), 617–629. doi: 10.1093/jnci/94.8.617 CrossRefGoogle ScholarPubMed
Hall, JM, Korach, KS. Stromal cell-derived factor 1, a novel target of estrogen receptor action, mediates the mitogenic effects of estradiol in ovarian and breast cancer cells. Mol Endocrinol. 2003; 17(5), 792–803. doi: 10.1210/me.2002-0438 CrossRefGoogle ScholarPubMed
Moll, F, Katsaros, D, Lazennec, G, et al. Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells. Oncogene. 2002; 21(7), 1097–1107. doi: 10.1038/sj.onc.1205171 CrossRefGoogle ScholarPubMed
O’Donnell, AJM, Macleod, KG, Burns, DJ, Smyth, JF, Langdon, SP. Estrogen receptor-alpha mediates gene expression changes and growth response in ovarian cancer cells exposed to estrogen. Endocr Relat Cancer. 2005; 12(4), 851–866. doi: 10.1677/erc.1.01039 CrossRefGoogle Scholar
Perniconi, SE, Simões, M de J, Simões, RDS, Haidar, MA, Baracat, EC, Soares, JMJ. Proliferation of the superficial epithelium of ovaries in senile female rats following oral administration of conjugated equine estrogens. Clinics (Sao Paulo). 2008; 63(3), 381–388. doi: 10.1590/s1807-59322008000300016 CrossRefGoogle ScholarPubMed
Joshi, CL, Nanda, BS, Saigal, RP. Histomorphological and histochemical studies on the female genitalia of ageing goat. IV. Histomorphology of ovarian cortex. Anat Anz. 1977; 141(1), 19–36.Google ScholarPubMed
Bulut, G, Kurdoglu, Z, Dönmez, YB, Kurdoglu, M, Erten, R. Effects of jnk inhibitor on inflammation and fibrosis in the ovary tissue of a rat model of polycystic ovary syndrome. Int J Clin Exp Pathol. 2015; 8(8), 8774–8785.Google ScholarPubMed
Amirikia, H, Savoy-Moore, RT, Sundareson, AS, Moghissi, KS. The effects of long-term androgen treatment on the ovary. Fertil Steril. 1986; 45(2), 202–208. doi: 10.1016/s0015-0282(16)49155-7 CrossRefGoogle ScholarPubMed
Emori, C, Sugiura, K. Role of oocyte-derived paracrine factors in follicular development. Anim Sci J. 2014; 85(6), 627–633. doi: 10.1111/asj.12200 CrossRefGoogle ScholarPubMed