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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2021

Open Access 01-12-2021 | Fertility | Research

Effect of the spatial–temporal specific theca cell Cyp17 overexpression on the reproductive phenotype of the novel TC17 mouse

Authors: Christian Secchi, Martina Belli, Tracy N. H. Harrison, Joseph Swift, CheMyong Ko, Antoni J. Duleba, Dwayne Stupack, R. Jeffrey Chang, Shunichi Shimasaki

Published in: Journal of Translational Medicine | Issue 1/2021

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Abstract

Background

In the ovarian follicle, the Theca Cells (TCs) have two main functions: preserving morphological integrity and, importantly, secreting steroid androgen hormones. TCs express the essential enzyme 17α-hydroxylase/17,20-desmolase (CYP17), which permits the conversion of pregnenolone and progesterone into androgens. Dysregulation of CYP17 enzyme activity due to an intrinsic ovarian defect is hypothesized to be a cause of hyperandrogenism in women. Androgen excess is observed in women with polycystic ovary syndrome (PCOS) resulting from excess endogenous androgen production, and in transgender males undergoing exogenous testosterone therapy after female sex assignment at birth. However, the molecular and morphological effects of Cyp17 overexpression and androgen excess on folliculogenesis is unknown.

Methods

In this work, seeking a comprehensive profiling of the local outcomes of the androgen excess in the ovary, we generated a transgenic mouse model (TC17) with doxycycline (Dox)-induced Cyp17 overexpression in a local and temporal manner. TC17 mice were obtained by a combination of the Tet-dependent expression system and the Cre/LoxP gene control system.

Results

Ovaries of Dox-treated TC17 mice overexpressed Cyp17 specifically in TCs, inducing high testosterone levels. Surprisingly, TC17 ovarian morphology resembled the human ovarian features of testosterone-treated transgender men (partially impaired folliculogenesis, hypertrophic or luteinized stromal cells, atretic follicles, and collapsed clusters). We additionally assessed TC17 fertility denoting a perturbation of the normal reproductive functions (e.g., low pregnancy rate and numbers of pups per litter). Finally, RNAseq analysis permitted us to identify dysregulated genes (Lhcgr, Fshr, Runx1) and pathways (Extra Cellular Matrix and Steroid Synthesis).

Conclusions

Our novel mouse model is a versatile tool to provide innovative insights into study the effects of Cyp17 overexpression and hyperandrogenism in the ovary.
Appendix
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Literature
1.
McNatty KP, Heath DA, Lundy T, Fidler AE, Quirke L, O’Connell A, Smith P, Groome N, Tisdall DJ. Control of early ovarian follicular development. J Reprod Fertil Suppl. 1999;54:3–16.PubMed
2.
McNatty KP, Moore LG, Hudson NL, Quirke LD, Lawrence SB, Reader K, Hanrahan JP, Smith P, Groome NP, Laitinen M, Ritvos O, Juengel JL. The oocyte and its role in regulating ovulation rate: a new paradigm in reproductive biology. Reproduction. 2004;128(4):379–86.PubMedCrossRef
3.
Tajima K, Orisaka M, Yata H, Goto K, Hosokawa K, Kotsuji F. Role of granulosa and theca cell interactions in ovarian follicular maturation. Microsc Res Tech. 2006;69(6):450–8.PubMedCrossRef
4.
Orisaka M, Tajima K, Tsang BK, Kotsuji F. Oocyte-granulosa-theca cell interactions during preantral follicular development. J Ovarian Res. 2009;2(1):9.PubMedPubMedCentralCrossRef
5.
McNatty KP, Makris A, DeGrazia C, Osathanondh R, Ryan KJ. The production of progesterone, androgens, and estrogens by granulosa cells, thecal tissue, and stromal tissue from human ovaries in vitro. J Clin Endocrinol Metab. 1979;49(5):687–99.PubMedCrossRef
6.
Young JM, McNeilly AS. Theca: the forgotten cell of the ovarian follicle. Reproduction. 2010;140(4):489–504.PubMedCrossRef
7.
Richards JS, Ren YA, Candelaria N, Adams JE, Rajkovic A. Ovarian follicular theca cell recruitment, differentiation, and impact on fertility: 2017 update. Endocr Rev. 2018;39(1):1–20.PubMedCrossRef
8.
Erickson GF, Magoffin DA, Dyer CA, Hofeditz C. The ovarian androgen producing cells: a review of structure/function relationships. Endocr Rev. 1985;6(3):371–99.PubMedCrossRef
9.
Ko C, Gieske MC, Al-Alem L, Hahn Y, Su W, Gong MC, Iglarz M, Koo Y. Endothelin-2 in ovarian follicle rupture. Endocrinology. 2006;147(4):1770–9.PubMedCrossRef
10.
Roberts AJ, Skinner MK. Mesenchymal-epithelial cell interactions in the ovary: estrogen-induced theca cell steroidogenesis. Mol Cell Endocrinol. 1990;72(1):R1-5.PubMedCrossRef
11.
Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic ovary syndrome (PCOS): the hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016;37(5):467–520.PubMedPubMedCentralCrossRef
12.
Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF, Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen E, Society P. The Androgen excess and PCOS society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009;91(2):456–88.PubMedCrossRef
13.
Yang MY, Fortune JE. Testosterone stimulates the primary to secondary follicle transition in bovine follicles in vitro. Biol Reprod. 2006;75(6):924–32.PubMedCrossRef
14.
Franks S. Animal models and the developmental origins of polycystic ovary syndrome: increasing evidence for the role of androgens in programming reproductive and metabolic dysfunction. Endocrinology. 2012;153(6):2536–8.PubMedCrossRef
15.
Caldwell AS, Middleton LJ, Jimenez M, Desai R, McMahon AC, Allan CM, Handelsman DJ, Walters KA. Characterization of reproductive, metabolic, and endocrine features of polycystic ovary syndrome in female hyperandrogenic mouse models. Endocrinology. 2014;155(8):3146–59.PubMedCrossRef
16.
Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA. Androgens stimulate early stages of follicular growth in the primate ovary. J Clin Invest. 1998;101(12):2622–9.PubMedPubMedCentralCrossRef
17.
Harlow CR, Shaw HJ, Hillier SG, Hodges JK. Factors influencing follicle-stimulating hormone-responsive steroidogenesis in marmoset granulosa cells: effects of androgens and the stage of follicular maturity. Endocrinology. 1988;122(6):2780–7.PubMedCrossRef
18.
Abbott DH, Barnett DK, Levine JE, Padmanabhan V, Dumesic DA, Jacoris S, Tarantal AF. Endocrine antecedents of polycystic ovary syndrome in fetal and infant prenatally androgenized female rhesus monkeys. Biol Reprod. 2008;79(1):154–63.PubMedCrossRef
19.
Gleicher N, Weghofer A, Barad DH. The role of androgens in follicle maturation and ovulation induction: friend or foe of infertility treatment? Reprod Biol Endocrinol. 2011;9:116.PubMedPubMedCentralCrossRef
20.
Smith DM, Tenney DY. Effects of steroids on mouse oocyte maturation in vitro. J Reprod Fertil. 1980;60(2):331–8.PubMedCrossRef
21.
Eppig JJ, Freter RR, Ward-Bailey PF, Schultz RM. Inhibition of oocyte maturation in the mouse: participation of cAMP, steroid hormones, and a putative maturation-inhibitory factor. Dev Biol. 1983;100(1):39–49.PubMedCrossRef
22.
Schultz RM, Montgomery RR, Ward-Bailey PF, Eppig JJ. Regulation of oocyte maturation in the mouse: possible roles of intercellular communication, cAMP, and testosterone. Dev Biol. 1983;95(2):294–304.PubMedCrossRef
23.
Anderiesz C, Trounson AO. The effect of testosterone on the maturation and developmental capacity of murine oocytes in vitro. Hum Reprod. 1995;10(9):2377–81.PubMedCrossRef
24.
Kimura S, Matsumoto T, Matsuyama R, Shiina H, Sato T, Takeyama K, Kato S. Androgen receptor function in folliculogenesis and its clinical implication in premature ovarian failure. Trends Endocrinol Metab. 2007;18(5):183–9.PubMedCrossRef
25.
Li M, Schatten H, Sun QY. Androgen receptor’s destiny in mammalian oocytes: a new hypothesis. Mol Hum Reprod. 2009;15(3):149–54.PubMedCrossRef
26.
Kidder GM, Vanderhyden BC. Bidirectional communication between oocytes and follicle cells: ensuring oocyte developmental competence. Can J Physiol Pharmacol. 2010;88(4):399–413.PubMedPubMedCentralCrossRef
27.
Liu X, Qiao P, Jiang A, Jiang J, Han H, Wang L, Ren C. Paracrine regulation of steroidogenesis in theca cells by granulosa cells derived from mouse preantral follicles. Biomed Res Int. 2015;2015: 925691.PubMedPubMedCentral
28.
Tajima K, Orisaka M, Mori T, Kotsuji F. Ovarian theca cells in follicular function. Reprod Biomed Online. 2007;15(5):591–609.PubMedCrossRef
29.
Tetsuka M, Hillier SG. Androgen receptor gene expression in rat granulosa cells: the role of follicle-stimulating hormone and steroid hormones. Endocrinology. 1996;137(10):4392–7.PubMedCrossRef
30.
Jakimiuk AJ, Weitsman SR, Navab A, Magoffin DA. Luteinizing hormone receptor, steroidogenesis acute regulatory protein, and steroidogenic enzyme messenger ribonucleic acids are overexpressed in thecal and granulosa cells from polycystic ovaries. J Clin Endocrinol Metab. 2001;86(3):1318–23.PubMed
31.
Manneras L, Cajander S, Holmang A, Seleskovic Z, Lystig T, Lonn M, Stener-Victorin E. A new rat model exhibiting both ovarian and metabolic characteristics of polycystic ovary syndrome. Endocrinology. 2007;148(8):3781–91.PubMedCrossRef
32.
Akhtar MK, Kelly SL, Kaderbhai MA. Cytochrome b(5) modulation of 17{alpha} hydroxylase and 17–20 lyase (CYP17) activities in steroidogenesis. J Endocrinol. 2005;187(2):267–74.PubMedCrossRef
33.
Patel SS, Beshay VE, Escobar JC, Carr BR. 17alpha-hydroxylase (CYP17) expression and subsequent androstenedione production in the human ovary. Reprod Sci. 2010;17(11):978–86.PubMedCrossRef
34.
McAllister JM, Kerin JF, Trant JM, Estabrook RW, Mason JI, Waterman MR, Simpson ER. Regulation of cholesterol side-chain cleavage and 17 alpha-hydroxylase/lyase activities in proliferating human theca interna cells in long term monolayer culture. Endocrinology. 1989;125(4):1959–66.PubMedCrossRef
35.
Su AI, Cooke MP, Ching KA, Hakak Y, Walker JR, Wiltshire T, Orth AP, Vega RG, Sapinoso LM, Moqrich A, Patapoutian A, Hampton GM, Schultz PG, Hogenesch JB. Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci USA. 2002;99(7):4465–70.PubMedPubMedCentralCrossRef
36.
Zhang P, Compagnone NA, Fiore C, Vigne JL, Culp P, Musci TJ, Mellon SH. Developmental gonadal expression of the transcription factor SET and its target gene, P450c17 (17alpha-hydroxylase/c17,20 lyase). DNA Cell Biol. 2001;20(10):613–24.PubMedCrossRef
37.
Rosenfield RL, Barnes RB, Cara JF, Lucky AW. Dysregulation of cytochrome P450c 17 alpha as the cause of polycystic ovarian syndrome. Fertil Steril. 1990;53(5):785–91.PubMedCrossRef
38.
Gilling-Smith C, Story H, Rogers V, Franks S. Evidence for a primary abnormality of thecal cell steroidogenesis in the polycystic ovary syndrome. Clin Endocrinol. 1997;47(1):93–9.CrossRef
39.
Nelson VL, Legro RS, Strauss JF 3rd, McAllister JM. Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol. 1999;13(6):946–57.PubMedCrossRef
40.
Comim FV, Teerds K, Hardy K, Franks S. Increased protein expression of LHCG receptor and 17alpha-hydroxylase/17-20-lyase in human polycystic ovaries. Hum Reprod. 2013;28(11):3086–92.PubMedCrossRef
41.
Pache TD, Chadha S, Gooren LJ, Hop WC, Jaarsma KW, Dommerholt HB, Fauser BC. Ovarian morphology in long-term androgen-treated female to male transsexuals. A human model for the study of polycystic ovarian syndrome? Histopathology. 1991;19(5):445–52.PubMedCrossRef
42.
Spinder T, Spijkstra JJ, Gooren LJ, Hompes PG, van Kessel H. Effects of long-term testosterone administration on gonadotropin secretion in agonadal female to male transsexuals compared with hypogonadal and normal women. J Clin Endocrinol Metab. 1989;68(1):200–7.PubMedCrossRef
43.
44.
Kauffman AS, Thackray VG, Ryan GE, Tolson KP, Glidewell-Kenney CA, Semaan SJ, Poling MC, Iwata N, Breen KM, Duleba AJ, Stener-Victorin E, Shimasaki S, Webster NJ, Mellon PL. A novel letrozole model recapitulates both the reproductive and metabolic phenotypes of polycystic ovary syndrome in female mice. Biol Reprod. 2015;93(3):69.PubMedPubMedCentralCrossRef
45.
46.
Maliqueo M, Sun M, Johansson J, Benrick A, Labrie F, Svensson H, Lonn M, Duleba AJ, Stener-Victorin E. Continuous administration of a P450 aromatase inhibitor induces polycystic ovary syndrome with a metabolic and endocrine phenotype in female rats at adult age. Endocrinology. 2013;154(1):434–45.PubMedCrossRef
47.
Belteki G, Haigh J, Kabacs N, Haigh K, Sison K, Costantini F, Whitsett J, Quaggin SE, Nagy A. Conditional and inducible transgene expression in mice through the combinatorial use of cre-mediated recombination and tetracycline induction. Nucleic Acids Res. 2005;33(5): e51.PubMedPubMedCentralCrossRef
48.
Yu HM, Liu B, Chiu SY, Costantini F, Hsu W. Development of a unique system for spatiotemporal and lineage-specific gene expression in mice. Proc Natl Acad Sci USA. 2005;102(24):8615–20.PubMedPubMedCentralCrossRef
49.
El Andaloussi A, Graves S, Meng F, Mandal M, Mashayekhi M, Aifantis I. Hedgehog signaling controls thymocyte progenitor homeostasis and differentiation in the thymus. Nat Immunol. 2006;7(4):418–26.PubMedCrossRef
50.
Maes C, Goossens S, Bartunkova S, Drogat B, Coenegrachts L, Stockmans I, Moermans K, Nyabi O, Haigh K, Naessens M, Haenebalcke L, Tuckermann JP, Tjwa M, Carmeliet P, Mandic V, David JP, Behrens A, Nagy A, Carmeliet G, Haigh JJ. Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones. EMBO J. 2010;29(2):424–41.PubMedCrossRef
51.
Pan W, Jin Y, Stanger B, Kiernan AE. Notch signaling is required for the generation of hair cells and supporting cells in the mammalian inner ear. Proc Natl Acad Sci USA. 2010;107(36):15798–803.PubMedPubMedCentralCrossRef
52.
Parsa S, Ramasamy SK, De Langhe S, Gupte VV, Haigh JJ, Medina D, Bellusci S. Terminal end bud maintenance in mammary gland is dependent upon FGFR2b signaling. Dev Biol. 2008;317(1):121–31.PubMedCrossRef
53.
Eshkar-Oren I, Viukov SV, Salameh S, Krief S, Oh CD, Akiyama H, Gerber HP, Ferrara N, Zelzer E. The forming limb skeleton serves as a signaling center for limb vasculature patterning via regulation of Vegf. Development. 2009;136(8):1263–72.PubMedCrossRef
54.
Noah TK, Kazanjian A, Whitsett J, Shroyer NF. SAM pointed domain ETS factor (SPDEF) regulates terminal differentiation and maturation of intestinal goblet cells. Exp Cell Res. 2010;316(3):452–65.PubMedCrossRef
55.
Pi M, Chen L, Huang M, Luo Q, Quarles LD. Parathyroid-specific interaction of the calcium-sensing receptor and G alpha q. Kidney Int. 2008;74(12):1548–56.PubMedPubMedCentralCrossRef
56.
Tang S, Snider P, Firulli AB, Conway SJ. Trigenic neural crest-restricted Smad7 over-expression results in congenital craniofacial and cardiovascular defects. Dev Biol. 2010;344(1):233–47.PubMedPubMedCentralCrossRef
57.
Wehn AK, Chapman DL. Tbx18 and Tbx15 null-like phenotypes in mouse embryos expressing Tbx6 in somitic and lateral plate mesoderm. Dev Biol. 2010;347(2):404–13.PubMedCrossRef
58.
Xu K, Nieuwenhuis E, Cohen BL, Wang W, Canty AJ, Danska JS, Coultas L, Rossant J, Wu MY, Piscione TD, Nagy A, Gossler A, Hicks GG, Hui CC, Henkelman RM, Yu LX, Sled JG, Gridley T, Egan SE. Lunatic fringe-mediated Notch signaling is required for lung alveogenesis. Am J Physiol Lung Cell Mol Physiol. 2010;298(1):L45-56.PubMedCrossRef
59.
Parsa S, Kuremoto K, Seidel K, Tabatabai R, Mackenzie B, Yamaza T, Akiyama K, Branch J, Koh CJ, Al Alam D, Klein OD, Bellusci S. Signaling by FGFR2b controls the regenerative capacity of adult mouse incisors. Development. 2010;137(22):3743–52.PubMedPubMedCentralCrossRef
60.
Bridges PJ, Koo Y, Kang DW, Hudgins-Spivey S, Lan ZJ, Xu X, DeMayo F, Cooney A, Ko C. Generation of Cyp17iCre transgenic mice and their application to conditionally delete estrogen receptor alpha (Esr1) from the ovary and testis. Genesis. 2008;46(9):499–505.PubMedPubMedCentralCrossRef
61.
Wang L, Feng Z, Wang X, Wang X, Zhang X. DEGseq: an R package for identifying differentially expressed genes from RNA-seq data. Bioinformatics. 2010;26(1):136–8.CrossRefPubMed
62.
63.
64.
Amirikia H, Savoy-Moore RT, Sundareson AS, Moghissi KS. The effects of long-term androgen treatment on the ovary. Fertil Steril. 1986;45(2):202–8.PubMedCrossRef
65.
Spinder T, Spijkstra JJ, van den Tweel JG, Burger CW, van Kessel H, Hompes PG, Gooren LJ. The effects of long term testosterone administration on pulsatile luteinizing hormone secretion and on ovarian histology in eugonadal female to male transsexual subjects. J Clin Endocrinol Metab. 1989;69(1):151–7.PubMedCrossRef
66.
Grynberg M, Fanchin R, Dubost G, Colau JC, Bremont-Weil C, Frydman R, Ayoubi JM. Histology of genital tract and breast tissue after long-term testosterone administration in a female-to-male transsexual population. Reprod Biomed Online. 2010;20(4):553–8.PubMedCrossRef
67.
Ikeda K, Baba T, Noguchi H, Nagasawa K, Endo T, Kiya T, Saito T. Excessive androgen exposure in female-to-male transsexual persons of reproductive age induces hyperplasia of the ovarian cortex and stroma but not polycystic ovary morphology. Hum Reprod. 2013;28(2):453–61.PubMedCrossRef
68.
Loverro G, Resta L, Dellino M, Edoardo DN, Cascarano MA, Loverro M, Mastrolia SA. Uterine and ovarian changes during testosterone administration in young female-to-male transsexuals. Taiwan J Obstet Gynecol. 2016;55(5):686–91.PubMedCrossRef
69.
Reeves G. Specific stroma in the cortex and medulla of the ovary. Cell types and vascular supply in relation to follicular apparatus and ovulation. Obstet Gynecol. 1971;37(6):832–44.PubMed
70.
Moravek MB. Gender-affirming hormone therapy for transgender men. Clin Obstet Gynecol. 2018;61(4):687–704.PubMedCrossRef
71.
Kinnear HM, Tomaszewski CE, Chang FL, Moravek MB, Xu M, Padmanabhan V, Shikanov A. The ovarian stroma as a new frontier. Reproduction. 2020;160(3):R25–39.PubMedPubMedCentralCrossRef
72.
Kinnear HM, Constance ES, David A, Marsh EE, Padmanabhan V, Shikanov A, Moravek MB. A mouse model to investigate the impact of testosterone therapy on reproduction in transgender men. Hum Reprod. 2019;34(10):2009–17.PubMedPubMedCentralCrossRef
73.
Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998;19(3):225–68.PubMedCrossRef
74.
Nicol B, Grimm SA, Chalmel F, Lecluze E, Pannetier M, Pailhoux E, Dupin-De-Beyssat E, Guiguen Y, Capel B, Yao HH. RUNX1 maintains the identity of the fetal ovary through an interplay with FOXL2. Nat Commun. 2019;10(1):5116.PubMedPubMedCentralCrossRef
75.
Ederveen EGT, van Hunsel F, Wondergem MJ, van Puijenbroek EP. Severe secondary polycythemia in a female-to-male transgender patient while using lifelong hormonal therapy: a patient’s perspective. Drug Saf Case Rep. 2018;5(1):6.PubMedPubMedCentralCrossRef
76.
Madsen MC, van Dijk D, Wiepjes CM, Conemans EB, Thijs A, den Heijer M. Erythrocytosis in a large cohort of trans men using testosterone: a long-term follow-up study on prevalence, determinants, and exposure years. J Clin Endocrinol Metab. 2021;106(6):1710–7.PubMedPubMedCentralCrossRef
77.
Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, Rosenthal SM, Safer JD, Tangpricha V, T’Sjoen GG. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2017;102(11):3869–903.PubMedCrossRef
78.
Coleman E, Bockting W, Botzer M, Cohen-Kettenis P, DeCuypere G, Feldman J, Fraser L, Green J, Knudson G, Meyer WJ, Monstrey S, Adler RK, Brown GR, Devor AH, Ehrbar R, Ettner R, Eyler E, Garofalo R, Karasic DH, Lev AI, Mayer G, Meyer-Bahlburg H, Hall BP, Pfaefflin F, Rachlin K, Robinson B, Schechter LS, Tangpricha V, van Trotsenburg M, Vitale A, Winter S, Whittle S, Wylie KR, Zucker K. Standards of care for the health of transsexual, transgender, and gender-nonconforming people, version 7. Int J Transgenderism. 2012;13(4):165–232.CrossRef
79.
McFarland J, Craig W, Clarke NJ, Spratt DI. Serum testosterone concentrations remain stable between injections in patients receiving subcutaneous testosterone. J Endocr Soc. 2017;1(8):1095–103.PubMedPubMedCentralCrossRef
80.
Nakamura A, Watanabe M, Sugimoto M, Sako T, Mahmood S, Kaku H, Nasu Y, Ishii K, Nagai A, Kumon H. Dose-response analysis of testosterone replacement therapy in patients with female to male gender identity disorder. Endocr J. 2013;60(3):275–81.PubMedCrossRef
81.
82.
Taub RL, Ellis SA, Neal-Perry G, Magaret AS, Prager SW, Micks EA. The effect of testosterone on ovulatory function in transmasculine individuals. Am J Obstet Gynecol. 2020;223(2):229.e221-8.CrossRef
83.
Radix A, Davis AM. Endocrine treatment of gender-dysphoric/gender-incongruent persons. JAMA. 2017;318(15):1491–2.PubMedCrossRef
84.
Lapinski J, Covas T, Perkins JM, Russell K, Adkins D, Coffigny MC, Hull S. Best practices in transgender health: a clinician’s guide. Prim Care. 2018;45(4):687–703.PubMedCrossRef
85.
Wakefield BW, Boguszewski KE, Cheney D, Taylor JF. Patterns of fertility discussions and referrals for youth at an interdisciplinary gender clinic. LGBT Health. 2019;6(8):417–21.PubMedCrossRef
86.
87.
Rafferty J, Committee on Psychosocial Aspects Of Child And Family Health, Committee on Adolescence, Section on Lesbian, Gay, Bisexual, and Transgender Health and Wellness. Ensuring comprehensive care and support for transgender and gender-diverse children and adolescents. Pediatrics. 2018. https://​doi.​org/​10.​1542/​peds.​2018-2162.CrossRefPubMed
Metadata
Title
Effect of the spatial–temporal specific theca cell Cyp17 overexpression on the reproductive phenotype of the novel TC17 mouse
Authors
Christian Secchi
Martina Belli
Tracy N. H. Harrison
Joseph Swift
CheMyong Ko
Antoni J. Duleba
Dwayne Stupack
R. Jeffrey Chang
Shunichi Shimasaki
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-021-03103-x

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