Male sexual differentiation is a complex process requiring the hormone-producing function of somatic cells in the gonad, including Sertoli cells and fetal Leydig cells (FLCs). FLCs are essential for virilization of the male embryo, but despite their crucial function, relatively little is known about their origins or development. Adult Leydig cells (ALCs), which arise at puberty, have been studied extensively and much of what has been learned about this cell population has been extrapolated to FLCs. This approach is problematic in that prevailing dogma in the field asserts that these 2 populations are distinct in origin. As such, it is imprudent to assume that FLCs arise and develop in a similar manner to ALCs. This review provides a critical assessment of studies performed on FLC populations, rather than those extrapolated from ALC studies to assemble a model for FLC origins and development. Furthermore, we underscore the need for conclusive identification of the source population of fetal Leydig cells.

Keywords:
Adrenogonadal primordium, Adult Leydig cells, Fetal Leydig cells, Leydig stem cells, Multipotent progenitor, SF-1, Testis development
1.
Adham IM, Emmen JM, Engel W: The role of the testicular factor INSL3 in establishing the gonadal position. Mol Cell Endocrinol 160:11–16 (2000).
2.
Adham IM, Steding G, Thamm T, Bullesbach EE, Schwabe C, et al: The overexpression of the Insl3 in female mice causes descent of the ovaries. Mol Endocrinol 16:244–252 (2002).
3.
Agoulnik AI: Relaxin and related peptides in male reproduction. Adv Exp Med Biol 612:49–64 (2007).
4.
Anand-Ivell RJ, Relan V, Balvers M, Coiffec-Dorval I, Fritsch M, et al: Expression of the insulin-like peptide 3 (INSL3) hormone-receptor (LGR8) system in the testis. Biol Reprod 74:945–953 (2006).
5.
Andrew A, Kramer B: An experimental investigation into the possible origin of pancreatic islet cells from rhombencephalic neurectoderm. J Embryol Exp Morphol 52:23–38 (1979).
6.
Andrew A, Kramer B, Rawdon BB: The origin of gut and pancreatic neuroendocrine (APUD) cells – the last word? J Pathol 186:117–118 (1998).
7.
Baker PJ, Sha JH, O’Shaughnessy PJ: Localisation and regulation of 17β-hydroxysteroid dehydrogenase type 3 mRNA during development in the mouse testis. Mol Cell Endocrinol 133:127–133 (1997).
8.
Baker PJ, Sha JA, McBride MW, Peng L, Payne AH, O’Shaughnessy PJ: Expression of 3β-hydroxysteroid dehydrogenase type I and type VI isoforms in the mouse testis during development. Eur J Biochem 260:911–917 (1999).
9.
Barker DJ: The fetal and infant origins of adult disease. BMJ 301:1111 (1990).
10.
Basciani S, Mariani S, Arizzi M, Ulisse S, Rucci N, et al: Expression of platelet-derived growth factor-A (PDGF-A), PDGF-B, and PDGF receptor-alpha and -beta during human testicular development and disease. J Clin Endocrinol Metab 87:2310–2319 (2002).
11.
Bhattacharyya S, Kulesa PM, Fraser SE: Vital labeling of embryonic cells using fluorescent dyes and proteins. Methods Cell Biol 87:187–210 (2008).
12.
Birnbacher R, Frisch H: Hormonal, genetic and clinical findings in an XX male. Horm Res 43:213–215 (1995).
13.
Bitgood MJ, Shen L, McMahon AP: Sertoli cell signaling by Desert hedgehog regulates the male germline. Curr Biol 6:298–304 (1996).
14.
Bogatcheva NV, Truong A, Feng S, Engel W, Adham IM, Agoulnik AI: GREAT/LGR8 is the only receptor for insulin-like 3 peptide. Mol Endocrinol 17:2639–2646 (2003).
15.
Brennan J, Tilmann C, Capel B: Pdgfr-α mediates testis cord organization and fetal Leydig cell development in the XY gonad. Genes Dev 17:800–810 (2003).
16.
Buehr M, Gu S, McLaren A: Mesonephric contribution to testis differentiation in the fetal mouse. Development 117:273–281 (1993).
17.
Chang C, Chen YT, Yeh SD, Xu Q, Wang RS, et al: Infertility with defective spermatogenesis and hypotestosteronemia in male mice lacking the androgen receptor in Sertoli cells. Proc Natl Acad Sci USA 101:6876–6881 (2004).
18.
Chau YM, Crawford PA, Woodson KG, Polish JA, Olson LM, Sadovsky Y: Role of steroidogenic-factor 1 in basal and 3′,5′-cyclic adenosine monophosphate-mediated regulation of cytochrome P450 side-chain cleavage enzyme in the mouse. Biol Reprod 57:765–771 (1997).
19.
Clark AM, Garland KK, Russell LD: Desert hedgehog (Dhh) gene is required in the mouse testis for formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules. Biol Reprod 63:1825–1838 (2000).
20.
Clark BJ, Wells J, King SR, Stocco DM: The purification, cloning, and expression of a novel luteinizing hormone-induced mitochondrial protein in MA-10 mouse Leydig tumor cells. Characterization of the steroidogenic acute regulatory protein (StAR). J Biol Chem 269:28314–28322 (1994).
21.
Davidoff MS, Schulze W, Middendorff R, Holstein AF: The Leydig cell of the human testis – a new member of the diffuse neuroendocrine system. Cell Tissue Res 271:429–439 (1993).
22.
Davidoff MS, Middendorff R, Kofuncu E, Muller D, Jezek D, Holstein AF: Leydig cells of the human testis possess astrocyte and oligodendrocyte marker molecules. Acta Histochem 104:39–49 (2002).
23.
De Gendt K, Swinnen JV, Saunders PT, Schoonjans L, Dewerchin M, et al: A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc Natl Acad Sci USA 101:1327–1332 (2004).
24.
De Gendt K, Atanassova N, Tan KA, de Franca LR, Parreira GG, et al: Development and function of the adult generation of Leydig cells in mice with Sertoli cell-selective or total ablation of the androgen receptor. Endocrinology 146:4117–4126 (2005).
25.
Emmen JM, McLuskey A, Adham IM, Engel W, Grootegoed JA, Brinkmann AO: Hormonal control of gubernaculum development during testis descent: gubernaculum outgrowth in vitro requires both insulin-like factor and androgen. Endocrinology 141:4720–4727 (2000a).
26.
Emmen JM, McLuskey A, Adham IM, Engel W, Verhoef-Post M, et al: Involvement of insulin-like factor 3 (Insl3) in diethylstilbestrol-induced cryptorchidism. Endocrinology 141:846–849 (2000b).
27.
Fechner PY, Marcantonio SM, Jaswaney V, Stetten G, Goodfellow PN, et al: The role of the sex-determining region Y gene in the etiology of 46,XX maleness. J Clin Endocrinol Metab 76:690–695 (1993).
28.
Gautier C, Levacher C, Saez JM, Habert R: Transforming growth factor beta1 inhibits steroidogenesis in dispersed fetal testicular cells in culture. Mol Cell Endocrinol 131:21–30 (1997).
29.
Ge RS, Dong Q, Sottas CM, Papadopoulos V, Zirkin BR, Hardy MP: In search of rat stem Leydig cells: identification, isolation, and lineage-specific development. Proc Natl Acad Sci USA 103:2719–2724 (2006).
30.
Gnessi L, Emidi A, Jannini EA, Carosa E, Maroder M, et al: Testicular development involves the spatiotemporal control of PDGFs and PDGF receptors gene expression and action. J Cell Biol 131:1105–1121 (1995).
31.
Gnessi L, Basciani S, Mariani S, Arizzi M, Spera G, et al: Leydig cell loss and spermatogenic arrest in platelet-derived growth factor (Pdgf)-a-deficient mice. J Cell Biol 149:1019–1026 (2000).
32.
Greco TL, Payne AH: Ontogeny of expression of the genes for steroidogenic enzymes P450 side-chain cleavage, 3 β-hydroxysteroid dehydrogenase, P450 17α-hydroxylase/C17–20 lyase, and P450 aromatase in fetal mouse gonads. Endocrinology 135:262–268 (1994).
33.
Greenfield A, Koopman P: SRY and mammalian sex determination. Curr Top Dev Biol 34:1–23 (1996).
34.
Habert R, Lejeune H, Saez JM: Origin, differentiation and regulation of fetal and adult Leydig cells. Mol Cell Endocrinol 179:47–74 (2001).
35.
Haider SG: Cell biology of Leydig cells in the testis. Int Rev Cytol 233:181–241 (2004).
36.
Haider SG, Passia D, Rommert FF: Histochemical demonstration of 11 β-hydroxysteroid dehydrogenase as a marker for Leydig cell maturation in rat. Acta Histochem Suppl 38:203–207 (1990).
37.
Haider SG, Laue D, Schwochau G, Hilscher B: Morphological studies on the origin of adult-type Leydig cells in rat testis. Ital J Anat Embryol 100 Suppl 1:535–541 (1995).
38.
Haider SG, Servos G, Tajtaraghi S, Berthold G, Mukhopadhyay AK, et al: Functional markers for fetal and postnatal differentiation of rat Leydig cells. Adv Exp Med Biol 424:143–144 (1997).
39.
Hatano O, Takayama K, Imai T, Waterman MR, Takakusu A, et al: Sex-dependent expression of a transcription factor, Ad4BP, regulating steroidogenic P-450 genes in the gonads during prenatal and postnatal rat development. Development 120:2787–2797 (1994).
40.
Hatano O, Takakusu A, Nomura M, Morohashi K: Identical origin of adrenal cortex and gonad revealed by expression profiles of Ad4BP/SF-1. Genes Cells 1:663–671 (1996).
41.
Heikkila M, Peltoketo H, Leppaluoto J, Ilves M, Vuolteenaho O, Vainio S: Wnt-4 deficiency alters mouse adrenal cortex function, reducing aldosterone production. Endocrinology 143:4358–4365 (2002).
42.
Holdcraft RW, Braun RE: Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids. Development 131:459–467 (2004).
43.
Hu L, Monteiro A, Johnston H, King P, O’Shaughnessy PJ: Expression of Cyp21a1 and Cyp11b1 in the fetal mouse testis. Reproduction 134:585–591 (2007).
44.
Huber K: The sympathoadrenal cell lineage: specification, diversification, and new perspectives. Dev Biol 298:335–343 (2006).
45.
Hutson JM, Hasthorpe S: Abnormalities of testicular descent. Cell Tissue Res 322:155–158 (2005).
46.
Ikeda Y, Luo X, Abbud R, Nilson JH, Parker KL: The nuclear receptor steroidogenic factor 1 is essential for the formation of the ventromedial hypothalamic nucleus. Mol Endocrinol 9:478–486 (1995).
47.
Jeyasuria P, Ikeda Y, Jamin SP, Zhao L, De Rooij DG, et al: Cell-specific knockout of steroidogenic factor 1 reveals its essential roles in gonadal function. Mol Endocrinol 18:1610–1619 (2004).
48.
Joyner AL, Zervas M: Genetic inducible fate mapping in mouse: establishing genetic lineages and defining genetic neuroanatomy in the nervous system. Dev Dyn 235:2376–2385 (2006).
49.
Karl J, Capel B: Sertoli cells of the mouse testis originate from the coelomic epithelium. Dev Biol 203:323–333 (1998).
50.
Kent J, Wheatley SC, Andrews JE, Sinclair AH, Koopman P: A male-specific role for SOX9 in vertebrate sex determination. Development 122:2813–2822 (1996).
51.
Kerr JB, Knell CM: The fate of fetal Leydig cells during the development of the fetal and postnatal rat testis. Development 103:535–544 (1988).
52.
Kirchgessner AL, Adlersberg MA, Gershon MD: Colonization of the developing pancreas by neural precursors from the bowel. Dev Dyn 194:142–154 (1992).
53.
Kirsch AJ, Bastian W, Cohen HL, Glassberg KI: Precocious puberty in a child with unilateral Leydig cell tumor of the testis following orchiopexy. J Urol 150:1483–1485 (1993).
54.
Kitamura K, Yanazawa M, Sugiyama N, Miura H, Iizuka-Kogo A, et al: Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. Nat Genet 32:359–369 (2002).
55.
Klonisch T, Fowler PA, Hombach-Klonisch S: Molecular and genetic regulation of testis descent and external genitalia development. Dev Biol 270:1–18 (2004).
56.
Koopman P, Munsterberg A, Capel B, Vivian N, Lovell-Badge R: Expression of a candidate sex-determining gene during mouse testis differentiation. Nature 348:450–452 (1990).
57.
Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R: Male development of chromosomally female mice transgenic for Sry. Nature 351:117–121 (1991).
58.
Kumagai J, Hsu SY, Matsumi H, Roh JS, Fu P, et al: INSL3/Leydig insulin-like peptide activates the LGR8 receptor important in testis descent. J Biol Chem 277:31283–31286 (2002).
59.
Lalli E, Melner MH, Stocco DM, Sassone-Corsi P: DAX-1 blocks steroid production at multiple levels. Endocrinology 139:4237–4243 (1998).
60.
Latronico AC, Arnhold IJ: Inactivating mutations of LH and FSH receptors – from genotype to phenotype. Pediatr Endocrinol Rev 4:28–31 (2006).
61.
Lawson KA: Fate mapping the mouse embryo. Int J Dev Biol 43:773–775 (1999).
62.
Leers-Sucheta S, Morohashi K, Mason JI, Melner MH: Synergistic activation of the human type II 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase promoter by the transcription factor steroidogenic factor-1/adrenal 4-binding protein and phorbol ester. J Biol Chem 272:7960–7967 (1997).
63.
Lei ZM, Mishra S, Zou W, Xu B, Foltz M, et al: Targeted disruption of luteinizing hormone/human chorionic gonadotropin receptor gene. Mol Endocrinol 15:184–200 (2001).
64.
Levacher C, Gautier C, Saez JM, Habert R: Immunohistochemical localization of transforming growth factor beta 1 and beta 2 in the fetal and neonatal rat ovary. Differentiation 61:45–51 (1996).
65.
Liu JP, Baker J, Perkins AS, Robertson EJ, Efstratiadis A: Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75:59–72 (1993).
66.
Lobo MV, Arenas MI, Alonso FJ, Gomez G, Bazan E, et al: Nestin, a neuroectodermal stem cell marker molecule, is expressed in Leydig cells of the human testis and in some specific cell types from human testicular tumours. Cell Tissue Res 316:369–376 (2004).
67.
Lording DW, De Kretser DM: Comparative ultrastructural and histochemical studies of the interstitial cells of the rat testis during fetal and postnatal development. J Reprod Fertil 29:261–269 (1972).
68.
Loveland KL, Zlatic K, Stein-Oakley A, Risbridger G, deKretser DM: Platelet-derived growth factor ligand and receptor subunit mRNA in the Sertoli and Leydig cells of the rat testis. Mol Cell Endocrinol 108:155–159 (1995).
69.
Luo X, Ikeda Y, Parker KL: A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 77:481–490 (1994).
70.
Luo X, Ikeda Y, Schlosser DA, Parker KL: Steroidogenic factor 1 is the essential transcript of the mouse Ftz-F1 gene. Mol Endocrinol 9:1233–1239 (1995).
71.
Ma X, Dong Y, Matzuk MM, Kumar TR: Targeted disruption of luteinizing hormone beta-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility. Proc Natl Acad Sci USA 101:17294–17299 (2004).
72.
Mack SO, Garrett WM, Guthrie HD: Absence of correlation between in situ expression of cytochrome P450 17α-hydroxylase/lyase and 3β-hydroxysteroid dehydrogenase/(Delta5-4) isomerase messenger ribonucleic acids and steroidogenesis during pubertal development in the rat testis. J Steroid Biochem Mol Biol 73:19–28 (2000).
73.
Mariani S, Basciani S, Arizzi M, Spera G, Gnessi L: PDGF and the testis. Trends Endocrinol Metab 13:11–17 (2002).
74.
Martineau J, Nordqvist K, Tilmann C, Lovell-Badge R, Capel B: Male-specific cell migration into the developing gonad. Curr Biol 7:958–968 (1997).
75.
Mayerhofer A, Lahr G, Seidl K, Eusterschulte B, Christoph A, Gratzl M: The neural cell adhesion molecule (NCAM) provides clues to the development of testicular Leydig cells. J Androl 17:223–230 (1996).
76.
McKinnell C, Sharpe RM, Mahood K, Hallmark N, Scott H, et al: Expression of insulin-like factor 3 protein in the rat testis during fetal and postnatal development and in relation to cryptorchidism induced by in utero exposure to di (n-Butyl) phthalate. Endocrinology 146:4536–4544 (2005).
77.
Mendis-Handagama SM, Risbridger GP, de Kretser DM: Morphometric analysis of the components of the neonatal and the adult rat testis interstitium. Int J Androl 10:525–534 (1987).
78.
Mendis-Handagama SM, Ariyaratne HB, Teunissen van Manen KR, Haupt RL: Differentiation of adult Leydig cells in the neonatal rat testis is arrested by hypothyroidism. Biol Reprod 59:351–357 (1998).
79.
Mendis-Handagama SM, Ariyaratne HB, Mrkonjich L, Ivell R: Expression of insulin-like peptide 3 in the postnatal rat Leydig cell lineage: timing and effects of triiodothyronine-treatment. Reproduction 133:479–485 (2007).
80.
Merchant-Larios H, Moreno-Mendoza N: Mesonephric stromal cells differentiate into Leydig cells in the mouse fetal testis. Exp Cell Res 244:230–238 (1998).
81.
Merchant-Larios H, Moreno-Mendoza N, Buehr M: The role of the mesonephros in cell differentiation and morphogenesis of the mouse fetal testis. Int J Dev Biol 37:407–415 (1993).
82.
Merlet J, Moreau E, Habert R, Racine C: Development of fetal testicular cells in androgen receptor deficient mice. Cell Cycle 6:2258–2262 (2007).
83.
Middendorff R, Davidoff M, Holstein AF: Neuroendocrine marker substances in human Leydig cells – changes by disturbances of testicular function. Andrologia 25:257–262 (1993).
84.
Mishina Y, Rey R, Finegold MJ, Matzuk MM, Josso N, et al: Genetic analysis of the Mullerian-inhibiting substance signal transduction pathway in mammalian sexual differentiation. Genes Dev 10:2577–2587 (1996).
85.
Morais da Silva S, Hacker A, Harley V, Goodfellow P, Swain A, Lovell-Badge R: Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds. Nat Genet 14:62–68 (1996).
86.
Morohashi K: The ontogenesis of the steroidogenic tissues. Genes Cells 2:95–106 (1997).
87.
Nachtigal MW, Hirokawa Y, Enyeart-VanHouten DL, Flanagan JN, Hammer GD, Ingraham HA: Wilms’ tumor 1 and Dax-1 modulate the orphan nuclear receptor SF-1 in sex-specific gene expression. Cell 93:445–454 (1998).
88.
Nef S, Parada LF: Cryptorchidism in mice mutant for Insl3. Nat Genet 22:295–299 (1999).
89.
O’Shaughnessy PJ, Baker PJ, Heikkila M, Vainio S, McMahon AP: Localization of 17β-hydroxysteroid dehydrogenase/17-ketosteroid reductase isoform expression in the developing mouse testis – androstenedione is the major androgen secreted by fetal/neonatal Leydig cells. Endocrinology 141:2631–2637 (2000).
90.
O’Shaughnessy PJ, Johnston H, Willerton L, Baker PJ: Failure of normal adult Leydig cell development in androgen-receptor-deficient mice. J Cell Sci 115:3491–3496 (2002).
91.
O’Shaughnessy PJ, Fleming LM, Jackson G, Hochgeschwender U, Reed P, Baker PJ: Adrenocorticotropic hormone directly stimulates testosterone production by the fetal and neonatal mouse testis. Endocrinology 144:3279–3284 (2003).
92.
O’Shaughnessy PJ, Baker PJ, Johnston H: The foetal Leydig cell – differentiation, function and regulation. Int J Androl 29:90–95; discussion 105–108 (2006).
93.
Olaso R, Gautier C, Levacher C, Durand P, Saez J, Habert R: The immunohistochemical localization of transforming growth factor-beta 2 in the fetal and neonatal rat testis. Mol Cell Endocrinol 126:165–172 (1997).
94.
Park SY, Tong M, Jameson JL: Distinct roles for steroidogenic factor 1 and desert hedgehog pathways in fetal and adult Leydig cell development. Endocrinology 148:3704–3710 (2007).
95.
Pictet RL, Rall LB, Phelps P, Rutter WJ: The neural crest and the origin of the insulin-producing and other gastrointestinal hormone-producing cells. Science 191:191–192 (1976).
96.
Pierucci-Alves F, Clark AM, Russell LD: A developmental study of the Desert hedgehog-null mouse testis. Biol Reprod 65:1392–1402 (2001).
97.
Qin Y, Bishop CE: Sox9 is sufficient for functional testis development producing fertile male mice in the absence of Sry. Hum Mol Genet 14:1221–1229 (2005).
98.
Racine C, Rey R, Forest MG, Louis F, Ferre A, et al: Receptors for anti-mullerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation. Proc Natl Acad Sci USA 95:594–599 (1998).
99.
Robinson J: Prenatal programming of the female reproductive neuroendocrine system by androgens. Reproduction 132:539–547 (2006).
100.
Roosen-Runge EC, Anderson D: The development of the interstitial cells in the testis of the albino rat. Acta Anat (Basel) 37:125–137 (1959).
101.
Rouiller-Fabre V, Lecref L, Gautier C, Saez JM, Habert R: Expression and effect of insulin-like growth factor I on rat fetal Leydig cell function and differentiation. Endocrinology 139:2926–2934 (1998).
102.
Sadovsky Y, Crawford PA, Woodson KG, Polish JA, Clements MA, et al: Mice deficient in the orphan receptor steroidogenic factor 1 lack adrenal glands and gonads but express P450 side-chain-cleavage enzyme in the placenta and have normal embryonic serum levels of corticosteroids. Proc Natl Acad Sci USA 92:10939–10943 (1995).
103.
Salvi R, Gomez F, Fiaux M, Schorderet D, Jameson JL, et al: Progressive onset of adrenal insufficiency and hypogonadism of pituitary origin caused by a complex genetic rearrangement within DAX-1. J Clin Endocrinol Metab 87:4094–4100 (2002).
104.
Soriano P: The PDGF alpha receptor is required for neural crest cell development and for normal patterning of the somites. Development 124:2691–2700 (1997).
105.
Stocco DM, Clark BJ: Role of the steroidogenic acute regulatory protein (StAR) in steroidogenesis. Biochem Pharmacol 51:197–205 (1996).
106.
Suzuki T, Kasahara M, Yoshioka H, Morohashi K, Umesono K: LXXLL-related motifs in Dax-1 have target specificity for the orphan nuclear receptors Ad4BP/SF-1 and LRH-1. Mol Cell Biol 23:238–249 (2003).
107.
Tabarin A, Achermann JC, Recan D, Bex V, Bertagna X, et al: A novel mutation in DAX1 causes delayed-onset adrenal insufficiency and incomplete hypogonadotropic hypogonadism. J Clin Invest 105:321–328 (2000).
108.
Teerds KJ, Dorrington JH: Localization of transforming growth factor beta 1 and beta 2 during testicular development in the rat. Biol Reprod 48:40–45 (1993).
109.
Tomboc M, Lee PA, Mitwally MF, Schneck FX, Bellinger M, Witchel SF: Insulin-like 3/relaxin-like factor gene mutations are associated with cryptorchidism. J Clin Endocrinol Metab 85:4013–4018 (2000).
110.
Tomiyama H, Hutson JM, Truong A, Agoulnik AI: Transabdominal testicular descent is disrupted in mice with deletion of insulinlike factor 3 receptor. J Pediatr Surg 38:1793–1798 (2003).
111.
Tran N, Servos G, Haider SG: Ultrastructure of cell contacts of fetal and adult Leydig cells in the rat: a systematic study from birth to senium. Anat Embryol (Berl) 211:273–282 (2006).
112.
Upadhyay S, Zamboni L: Ectopic germ cells: natural model for the study of germ cell sexual differentiation. Proc Natl Acad Sci USA 79:6584–6588 (1982).
113.
Val P, Jeays-Ward K, Swain A: Identification of a novel population of adrenal-like cells in the mammalian testis. Dev Biol 299:250–256 (2006).
114.
Vidal VP, Chaboissier MC, de Rooij DG, Schedl A: Sox9 induces testis development in XX transgenic mice. Nat Genet 28:216–217 (2001).
115.
Vilain E, McCabe ER: Mammalian sex determination: from gonads to brain. Mol Genet Metab 65:74–84 (1998).
116.
Wang G, Hardy MP: Development of Leydig cells in the insulin-like growth factor-I (Igf-I) knockout mouse: effects of Igf-I replacement and gonadotropic stimulation. Biol Reprod 70:632–639 (2004).
117.
Wang GM, Ge RS, Latif SA, Morris DJ, Hardy MP: Expression of 11β-hydroxylase in rat Leydig cells. Endocrinology 143:621–626 (2002).
118.
Wang GM, O’Shaughnessy PJ, Chubb C, Robaire B, Hardy MP: Effects of insulin-like growth factor I on steroidogenic enzyme expression levels in mouse Leydig cells. Endocrinology 144:5058–5064 (2003).
119.
Wang ZJ, Jeffs B, Ito M, Achermann JC, Yu RN, et al: Aromatase (Cyp19) expression is up-regulated by targeted disruption of Dax1. Proc Natl Acad Sci USA 98:7988–7993 (2001).
120.
Yao HH, Capel B: Disruption of testis cords by cyclopamine or forskolin reveals independent cellular pathways in testis organogenesis. Dev Biol 246:356–365 (2002).
121.
Yao HH, Whoriskey W, Capel B: Desert Hedgehog/Patched 1 signaling specifies fetal Leydig cell fate in testis organogenesis. Genes Dev 16:1433–1440 (2002).
122.
Yu RN, Ito M, Saunders TL, Camper SA, Jameson JL: Role of Ahch in gonadal development and gametogenesis. Nat Genet 20:353–357 (1998).
123.
Zazopoulos E, Lalli E, Stocco DM, Sassone-Corsi P: DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis. Nature 390:311–315 (1997).
124.
Zhang FP, Poutanen M, Wilbertz J, Huhtaniemi I: Normal prenatal but arrested postnatal sexual development of luteinizing hormone receptor knockout (LuRKO) mice. Mol Endocrinol 15:172–183 (2001).
125.
Zimmermann S, Steding G, Emmen JM, Brinkmann AO, Nayernia K, et al: Targeted disruption of the Insl3 gene causes bilateral cryptorchidism. Mol Endocrinol 13:681–691 (1999).
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