Optimisation of hormonal treatment to improve follicular development in one-day-old mice ovaries cultured under in vitro condition
Tahoura Torkzadeh A # , Zahra Asadi A B # , Mohammad Jafari Atrabi C D , Farideh Eivazkhani E , Maryam Khodadi A , Samira Hajiaghalou E , Vahid Akbarinejad
A * and Rouhollah Fathi E *
A
B
C
D
E
Handling Editor: Jennifer Juengel
Abstract
Base medium containing knock-out serum replacement (KSR) has been found to support formation and maintenance of follicles in one-day-old mice ovaries, but has not been shown to properly support activation and growth of primordial follicles.
The present study was conducted to tailor the hormonal content of base medium containing KSR to enhance development of primordial follicles in neonatal ovaries.
One-day-old mice ovaries were initially cultured with base medium for four days, and then, different hormonal treatments were added to the culture media and the culture was proceeded for four additional days until day eight. Ovaries were collected for histological and molecular assessments on days four and eight.
In experiment I, the main and interactive effects of FSH and testosterone were investigated and FSH promoted activation of primordial follicles and development of primary and preantral follicles, and upregulated genes of phosphoinositide 3-kinase (Pi3k), KIT ligand (Kitl), growth differentiation factor 9 (Gdf9) and follicle stimulating hormone receptor (Fshr) (P < 0.05). Combination of testosterone and FSH, moreover, boosted gene expression of bone morphogenetic protein 15 (Bmp15), Connexin-43 (Cx43) and luteinising hormone and choriogonadotropin receptor (Lhcgr) (P < 0.05). In experiment II, the effect of various gonadotropins including FSH, equine chorionic gonadotropin (eCG) and human menopausal gonadotropin (hMG) on cultured ovaries was assessed and hMG supported development of primary follicles greater than eCG and FSH did (P < 0.05). Additionally, eCG and hMG increased gene expression of Lhcgr (P < 0.05), but FSH did not (P > 0.05).
Supplementation of culture medium containing KSR with gonadotropins, particularly hMG, could improve follicular growth and expression of factors regulating follicular development.
This study was a step forward in formulating an optimal medium for development of follicles in cultured one-day-old mice ovaries.
Keywords: assisted reproductive technique (ART), folliculogenesis, FSH, LH, one-day-old mouse ovary, ovarian follicle development, premature ovarian failure (POF), premature ovarian insufficiency (POI), regenerative medicine, testosterone.
References
Abedel-Majed MA, Romereim SM, Davis JS, Cupp AS (2019) Perturbations in lineage specification of granulosa and theca cells may alter corpus luteum formation and function. Frontiers in Endocrinology 10, 832.
| Crossref | Google Scholar | PubMed |
Alam H, Maizels ET, Park Y, Ghaey S, Feiger ZJ, Chandel NS, Hunzicker-Dunn M (2004) Follicle-stimulating hormone activation of hypoxia-inducible factor-1 by the phosphatidylinositol 3-kinase/AKT/Ras homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) pathway is necessary for induction of select protein markers of follicular differentiation. The Journal of Biological Chemistry 279(19), 19431-19440.
| Crossref | Google Scholar | PubMed |
Alborzi P, Jafari Atrabi M, Akbarinejad V, Khanbabaei R, 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 2020, 1-8.
| Google Scholar |
Allan CM, Wang Y, Jimenez M, Marshan B, Spaliviero J, Illingworth P, Handelsman DJ (2006) Follicle-stimulating hormone increases primordial follicle reserve in mature female hypogonadal mice. Journal of Endocrinology 188(3), 549-557.
| Crossref | Google Scholar | PubMed |
Amorim CA, Shikanov A (2016) The artificial ovary: current status and future perspectives. Future Oncology 12(20), 2323-2332.
| Crossref | Google Scholar | PubMed |
Atrabi MJ, Akbarinejad V, Khanbabaee R, Dalman A, Amorim CA, Najar-Asl M, Valojerdi MR, Fathi R (2019) Formation and activation induction of primordial follicles using granulosa and cumulus cells conditioned media. Journal of Cellular Physiology 234(7), 10148-10156.
| Crossref | Google Scholar | PubMed |
Atrabi MJ, Alborzi P, Akbarinejad V, 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), 468-475.
| Crossref | Google Scholar | PubMed |
Bukovský A, Chen TT, Wimalasena J, Caudle MR (1993) Cellular localization of luteinizing hormone receptor immunoreactivity in the ovaries of immature, gonadotropin-primed and normal cycling rats. Biology of Reproduction 48(6), 1367-1382.
| Crossref | Google Scholar | PubMed |
Casarini L, Crépieux P (2019) Molecular mechanisms of action of FSH. Frontiers in Endocrinology 10, 305.
| Crossref | Google Scholar | PubMed |
Chen X-Y, Xia H-X, Guan H-Y, Li B, Zhang W (2016) Follicle loss and apoptosis in cyclophosphamide-treated mice: what’s the matter? International Journal of Molecular Sciences 17, 836.
| Crossref | Google Scholar | PubMed |
Chen F, Wang Y, Liu Q, Hu J, Jin J, Ma Z, Zhang J (2020) ERO1α promotes testosterone secretion in hCG-stimulated mouse Leydig cells via activation of the PI3K/AKT/mTOR signaling pathway. Journal of Cellular Physiology 235(7–8), 5666-5678.
| Crossref | Google Scholar | PubMed |
Cortvrindt R, Smitz J, Van Steirteghem AC (1997) Assessment of the need for follicle stimulating hormone in early preantral mouse follicle culture in vitro. Human Reproduction (Oxford, England) 12(4), 759-768.
| Crossref | Google Scholar | PubMed |
Cossigny DA, Findlay JK, Drummond AE (2012) The effects of FSH and activin A on follicle development in vitro. Reproduction 143(2), 221-229.
| Crossref | Google Scholar | PubMed |
Del Castillo LM, Buigues A, Rossi V, Soriano MJ, Martinez J, De Felici M, Lamsira HK, Di Rella F, Klinger FG, Pellicer A, Herraiz S (2021) The cyto-protective effects of LH on ovarian reserve and female fertility during exposure to gonadotoxic alkylating agents in an adult mouse model. Human Reproduction 36(9), 2514-2528.
| Crossref | Google Scholar | PubMed |
Driancourt MA, Reynaud K, Cortvrindt R, Smitz J (2000) Roles of KIT and KIT LIGAND in ovarian function. Reviews of Reproduction 5(3), 143-152.
| Crossref | Google Scholar | PubMed |
Durlinger ALL, Kramer P, Karels B, de Jong FH, Uilenbroek JTJ, Grootegoed JA, Themmen APN (1999) Control of primordial follicle recruitment by anti-Müllerian hormone in the mouse ovary. Endocrinology 140(12), 5789-5796.
| Crossref | Google Scholar | PubMed |
Eppig JJ, O’Brien MJ (1996) Development in vitro of mouse oocytes from primordial follicles. Biology of Reproduction 54(1), 197-207.
| Crossref | Google Scholar | PubMed |
Erickson GF, Wang C, Hsueh AJW (1979) FSH induction of functional LH receptors in granulosa cells cultured in a chemically defined medium. Nature 279(5711), 336-338.
| Crossref | Google Scholar | PubMed |
Fan H-Y, Liu Z, Cahill N, Richards JAS (2008) Targeted disruption of pten in ovarian granulosa cells enhances ovulation and extends the life span of luteal cells. Molecular Endocrinology 22(9), 2128-2140.
| Crossref | Google Scholar | PubMed |
Filatov MA, Nikishin DA, Khramova YV, Semenova ML (2019) Reference genes selection for real-time quantitative PCR analysis in mouse germinal vesicle oocytes. Zygote 27(6), 392-397.
| Crossref | Google Scholar | PubMed |
Findlay JK, Hutt KJ, Hickey M, Anderson RA (2015) How is the number of primordial follicles in the ovarian reserve established? Biology of Reproduction 93(5), 111.
| Crossref | Google Scholar | PubMed |
Ford EA, Beckett EL, Roman SD, McLaughlin EA, Sutherland JM (2020) Advances in human primordial follicle activation and premature ovarian insufficiency. Reproduction 159(1), R15-R29.
| Crossref | Google Scholar | PubMed |
Fortune JE, Kito S, Wandji S-A, Srsen V (1998) Activation of bovine and baboon primordial follicles in vitro. Theriogenology 49(2), 441-449.
| Crossref | Google Scholar | PubMed |
Fujibe Y, Baba T, Nagao S, Adachi S, Ikeda K, Morishita M, Kuno Y, Suzuki M, Mizuuchi M, Honnma H, Endo T, Saito T (2019) Androgen potentiates the expression of FSH receptor and supports preantral follicle development in mice. Journal of Ovarian Research 12(1), 31.
| Crossref | Google Scholar | PubMed |
George JW, Dille EA, Heckert LL (2011) Current concepts of follicle-stimulating hormone receptor gene regulation. Biology of Reproduction 84(1), 7-17.
| Crossref | Google Scholar | PubMed |
Gilchrist RB, Lane M, Thompson JG (2008) Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Human Reproduction Update 14(2), 159-177.
| Crossref | Google Scholar | PubMed |
Gonzalez-Robayna IJ, Falender AE, Ochsner S, Firestone GL, Richards JAS (2000) Follicle-stimulating hormone (FSH) stimulates phosphorylation and activation of protein kinase B (PKB/Akt) and serum and glucocorticoid-lnduced kinase (Sgk): evidence for a kinase-independent signaling by FSH in granulosa cells. Molecular Endocrinology 14(8), 1283-1300.
| Crossref | Google Scholar | PubMed |
Herndon MK, Law NC, Donaubauer EM, Kyriss B, Hunzicker-Dunn M (2016) Forkhead box O member FOXO1 regulates the majority of follicle-stimulating hormone responsive genes in ovarian granulosa cells. Molecular and Cellular Endocrinology 434, 116-126.
| Crossref | Google Scholar | PubMed |
Honda A, Hirose M, Hara K, Matoba S, Inoue K, Miki H, Hiura H, Kanatsu-Shinohara M, Kanai Y, Kono T, Shinohara T, Ogura A (2007) Isolation, characterization, and in vitro and in vivo differentiation of putative thecal stem cells. Proceedings of the National Academy of Sciences of the United States of America 104(30), 12389-12394.
| Crossref | Google Scholar | PubMed |
Hreinsson JG, Scott JE, Rasmussen C, Swahn ML, Hsueh AJW, 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 & Metabolism 87(1), 316-321.
| Crossref | Google Scholar | PubMed |
Huang C, Gu H, Zhang W, Herrmann JL, Wang M (2010) Testosterone-down-regulated Akt pathway during cardiac ischemia/reperfusion: a mechanism involving BAD, Bcl-2 and FOXO3a. Journal of Surgical Research 164(1), e1-e11.
| Crossref | Google Scholar | PubMed |
Hunzicker-Dunn M, Maizels ET (2006) FSH signaling pathways in immature granulosa cells that regulate target gene expression: branching out from protein kinase A. Cellular Signalling 18(9), 1351-1359.
| Crossref | Google Scholar | PubMed |
Hunzicker-Dunn ME, Lopez-Biladeau B, Law NC, Fiedler SE, Carr DW, Maizels ET (2012) PKA and GAB2 play central roles in the FSH signaling pathway to PI3K and AKT in ovarian granulosa cells. Proceedings of the National Academy of Sciences of the United States of America 109(44), E2979-E2988.
| Crossref | Google Scholar | PubMed |
Hussein MR (2005) Apoptosis in the ovary: molecular mechanisms. Human Reproduction Update 11, 162-178.
| Crossref | Google Scholar | PubMed |
Hutt KJ, McLaughlin EA, Holland MK (2006) KIT/KIT ligand in mammalian oogenesis and folliculogenesis: roles in rabbit and murine ovarian follicle activation and oocyte growth. Biology of Reproduction 75(3), 421-433.
| Crossref | Google Scholar | PubMed |
Jewgenow K, Paris MCJ (2006) Preservation of female germ cells from ovaries of cat species. Theriogenology 66(1), 93-100.
| Crossref | Google Scholar | PubMed |
Joyce IM, Pendola FL, Wigglesworth K, Eppig JJ (1999) Oocyte regulation of kit ligand expression in mouse ovarian follicles. Developmental Biology 214(2), 342-353.
| Crossref | Google Scholar | PubMed |
Juneja SC, Barr KJ, Enders GC, Kidder GM (1999) Defects in the germ line and gonads of mice lacking connexin43. Biology of Reproduction 60(5), 1263-1270.
| Crossref | Google Scholar | PubMed |
Kedem A, Fisch B, Garor R, Ben-Zaken A, Gizunterman T, Felz C, Ben-Haroush A, Kravarusic D, 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 & Metabolism 96(8), E1246-E1254.
| Crossref | Google Scholar | PubMed |
Kerr JB, Duckett R, Myers M, Britt KL, Mladenovska T, Findlay JK (2006) Quantification of healthy follicles in the neonatal and adult mouse ovary: evidence for maintenance of primordial follicle supply. Reproduction 132(1), 95-109.
| Crossref | Google Scholar | PubMed |
Khodadi M, Atrabi MJ, Torkzadeh T, Fazli M, Akbarinejad V, 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.
| Crossref | Google Scholar | PubMed |
Kim SY, 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), 119-125.
| Google Scholar | PubMed |
Kishi H, Kitahara Y, Imai F, Nakao K, Suwa H (2018) Expression of the gonadotropin receptors during follicular development. Reproductive Medicine and Biology 17(1), 11-19.
| Crossref | Google Scholar | PubMed |
Kreeger PK, Fernandes NN, Woodruff TK, Shea LD (2005) Regulation of mouse follicle development by follicle-stimulating hormone in a three-dimensional in vitro culture system is dependent on follicle stage and dose. Biology of Reproduction 73(5), 942-950.
| Crossref | Google Scholar | PubMed |
Laird M, Thomson K, Fenwick M, Mora J, Franks S, 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), 920-935.
| Crossref | Google Scholar | PubMed |
Li L, Shi X, Shi Y, Wang Z (2021) The signaling pathways involved in ovarian follicle development. Frontiers in Physiology 12, 730196.
| Crossref | Google Scholar | PubMed |
Liu W-X, Zhang Y-J, Wang Y-F, Klinger FG, Tan S-J, Farini D, De Felici M, Shen W, Cheng S-F (2021) Protective mechanism of luteinizing hormone and follicle-stimulating hormone against nicotine-induced damage of mouse early folliculogenesis. Frontiers in Cell and Developmental Biology 9, 723388.
| Crossref | Google Scholar | PubMed |
Lunenfeld B, Bilger W, Longobardi S, Alam V, D’Hooghe T, Sunkara SK (2019) The development of gonadotropins for clinical use in the treatment of infertility. Frontiers in Endocrinology 10, 429.
| Crossref | Google Scholar | PubMed |
Magamage MPS, Zengyo M, Moniruzzaman M, Miyano T (2011) Testosterone induces activation of porcine primordial follicles in vitro. Reproductive Medicine and Biology 10(1), 21-30.
| Crossref | Google Scholar | PubMed |
Makker A, Goel MM, Mahdi AA (2014) PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: an update. Journal of Molecular Endocrinology 53(3), R103-R118.
| Crossref | Google Scholar | PubMed |
Mamo S, Gal AB, Bodo S, Dinnyes A (2007) Quantitative evaluation and selection of reference genes in mouse oocytes and embryos cultured in vivo and in vitro. BMC Developmental Biology 7, 14.
| Crossref | Google Scholar | PubMed |
McGee EA, Hsueh AJW (2000) Initial and cyclic recruitment of ovarian follicles. Endocrine Reviews 21(2), 200-214.
| Crossref | Google Scholar | PubMed |
McGee EA, Perlas E, LaPolt PS, Tsafriri A, Hsueh AJW (1997) Follicle-stimulating hormone enhances the development of preantral follicles in juvenile rats. Biology of Reproduction 57(5), 990-998.
| Crossref | Google Scholar | PubMed |
McLaughlin M, Albertini DF, Wallace WHB, Anderson RA, Telfer EE (2018) Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system. Molecular Human Reproduction 24(3), 135-142.
| Crossref | Google Scholar | PubMed |
Morohaku K, Tanimoto R, Sasaki K, Kawahara-Miki R, Kono T, Hayashi K, Hirao Y, 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), 9021-9026.
| Crossref | Google Scholar | PubMed |
Nagashima JB, Wildt DE, Travis AJ, Songsasen N (2019) Activin promotes growth and antral cavity expansion in the dog ovarian follicle. Theriogenology 129, 168-177.
| Crossref | Google Scholar | PubMed |
Nilsson E, Skinner MK (2001) Cellular interactions that control primordial follicle development and folliculogenesis. Journal of the Society for Gynecologic Investigation 8(1 Suppl), S17-S20.
| Crossref | Google Scholar | PubMed |
O’Brien MJ, Pendola JK, Eppig JJ (2003) A revised protocol for in vitro development of mouse oocytes from primordial follicles dramatically improves their developmental competence. Biology of Reproduction 68(5), 1682-1686.
| Crossref | Google Scholar | PubMed |
Oktay K, Briggs D, Gosden RG (1997) Ontogeny of follicle-stimulating hormone receptor gene expression in isolated human ovarian follicles. The Journal of Clinical Endocrinology & Metabolism 82(11), 3748-3751.
| Crossref | Google Scholar | PubMed |
Ono YJ, Tanabe A, Nakamura Y, Yamamoto H, Hayashi A, Tanaka T, Sasaki H, Hayashi M, Terai Y, Ohmichi M (2014) A low-testosterone state associated with endometrioma leads to the apoptosis of granulosa cells. PLoS ONE 9(12), e115618.
| Crossref | Google Scholar | PubMed |
Orisaka M, Tajima K, Tsang BK, Kotsuji F (2009) Oocyte-granulosa-theca cell interactions during preantral follicular development. Journal of Ovarian Research 2(1), 9.
| Crossref | Google Scholar | PubMed |
Otsuka F, McTavish KJ, Shimasaki S (2011) Integral role of GDF-9 and BMP-15 in ovarian function. Molecular Reproduction and Development 78(1), 9-21.
| Crossref | Google Scholar | PubMed |
Pepling ME (2006) From primordial germ cell to primordial follicle: mammalian female germ cell development. Genesis 44(12), 622-632.
| Crossref | Google Scholar | PubMed |
Persani L, Rossetti R, Di Pasquale E, Cacciatore C, 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), 869-883.
| Crossref | Google Scholar | PubMed |
Qureshi AI, Nussey SS, Bano G, Musonda P, Whitehead SA, Mason HD (2008) Testosterone selectively increases primary follicles in ovarian cortex grafted onto embryonic chick membranes: relevance to polycystic ovaries. Reproduction 136(2), 187-194.
| Crossref | Google Scholar | PubMed |
Richards JAS, Ren YA, Candelaria N, Adams JE, Rajkovic A (2018) Ovarian follicular theca cell recruitment, differentiation, and impact on fertility: 2017 update. Endocrine Reviews 39(1), 1-20.
| Crossref | Google Scholar | PubMed |
Rossi V, Lispi M, Longobardi S, Mattei M, Di Rella F, Salustri A, De Felici M, Klinger FG (2017) LH prevents cisplatin-induced apoptosis in oocytes and preserves female fertility in mouse. Cell Death & Differentiation 24(1), 72-82.
| Crossref | Google Scholar | PubMed |
Roy SK, Albee L (2000) Requirement for follicle-stimulating hormone action in the formation of primordial follicles during perinatal ovarian development in the hamster. Endocrinology 141(12), 4449-4456.
| Crossref | Google Scholar | PubMed |
Santiquet N, Robert C, Richard FJ (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.
| Crossref | Google Scholar | PubMed |
Sarma UC, Findlay JK, Hutt KJ (2019) Oocytes from stem cells. Best Practice & Research Clinical Obstetrics & Gynaecology 55, 14-22.
| Crossref | Google Scholar | PubMed |
Sen A, Prizant H, Light A, Biswas A, Hayes E, Lee H-J, Barad D, Gleicher N, Hammes SR (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), 3008-3013.
| Crossref | Google Scholar | PubMed |
Shen M, Liu Z, Li B, Teng Y, Zhang J, Tang Y, Sun S-C, 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.
| Crossref | Google Scholar | PubMed |
Silva JRV, van den Hurk R, de Matos MHT, dos Santos RR, Pessoa C, de Moraes MO, de Figueiredo JR (2004) Influences of FSH and EGF on primordial follicles during in vitro culture of caprine ovarian cortical tissue. Theriogenology 61(9), 1691-1704.
| Crossref | Google Scholar | PubMed |
Spears N, Murray AA, Allison V, Boland NI, Gosden RG (1998) Role of gonadotrophins and ovarian steroids in the development of mouse follicles in vitro. Journal of Reproduction Fertility 113(1), 19-26.
| Crossref | Google Scholar | PubMed |
Teilmann SC (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), 27-35.
| Crossref | Google Scholar | PubMed |
Telfer EE, McLaughlin M, Ding C, Thong KJ (2008) A two-step serum-free culture system supports development of human oocytes from primordial follicles in the presence of activin. Human Reproduction 23(5), 1151-1158.
| Crossref | Google Scholar | PubMed |
Tepekoy F, Akkoyunlu G (2016) The effect of FSH and activin A on Akt and MAPK1/3 phosphorylation in cultured bovine ovarian cortical strips. Journal of Ovarian Research 9, 13.
| Crossref | Google Scholar | PubMed |
Tingen CM, Bristol-Gould SK, Kiesewetter SE, Wellington JT, Shea L, Woodruff TK (2009) Prepubertal primordial follicle loss in mice is not due to classical apoptotic pathways. Biology of Reproduction 81, 16-25.
| Crossref | Google Scholar | PubMed |
Ueno S, Takahashi M, Manganaro TF, Ragin RC, Donahoe PK (1989) Cellular localization of Müllerian inhibiting substance in the developing rat ovary. Endocrinology 124(2), 1000-1006.
| Crossref | Google Scholar | PubMed |
Vitt UA, Kloosterboer HJ, Rose UM, Mulders JWM, Kiesel PS, Bete S, Nayudu PL (1998) Isoforms of human recombinant follicle-stimulating hormone: comparison of effects on murine follicle development in vitro. Biology of Reproduction 59(4), 854-861.
| Crossref | Google Scholar | PubMed |
Vitt UA, McGee EA, Hayashi M, Hsueh AJW (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), 3814-3820.
| Crossref | Google Scholar | PubMed |
Weng Q, Wang H, Medan MS, Jin W, Xia G, Watanabe G, Taya K (2006) Expression of inhibin/activin subunits in the ovaries of fetal and neonatal mice. Journal of Reproduction and Development 52(5), 607-616.
| Crossref | Google Scholar | PubMed |
Wright CS, Hovatta O, Margara R, Trew G, Winston RML, Franks S, Hardy K (1999) Effects of follicle-stimulating hormone and serum substitution on the in-vitro growth of human ovarian follicles. Human Reproduction 14(6), 1555-1562.
| Crossref | Google Scholar | PubMed |
Wu J, Nayudu PL, Kiesel PS, Michelmann HW (2000) Luteinizing hormone has a stage-limited effect on preantral follicle development in vitro. Biology of Reproduction 63(1), 320-327.
| Crossref | Google Scholar | PubMed |
Yang MY, Fortune JE (2006) Testosterone stimulates the primary to secondary follicle transition in bovine follicles in vitro. Biology of Reproduction 75(6), 924-932.
| Crossref | Google Scholar | PubMed |
Yoo M, Tanaka T, Konishi H, Tanabe A, Taniguchi K, Komura K, Hayashi M, Ohmichi M (2020) The protective effect of testosterone on the ovarian reserve during cyclophosphamide treatment. OncoTargets and Therapy 13, 2987-2995.
| Crossref | Google Scholar |
Young JM, McNeilly AS (2010) Theca: the forgotten cell of the ovarian follicle. Reproduction 140(4), 489-504.
| Crossref | Google Scholar | PubMed |
Zhang M, Shi H, Segaloff DL, Van Voorhis BJ (2001) Expression and localization of luteinizing hormone receptor in the female mouse reproductive tract. Biology of Reproduction 64(1), 179-187.
| Google Scholar | PubMed |
