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Testis Development and Descent

  • Reference work entry
  • First Online:
Endocrinology of the Testis and Male Reproduction

Part of the book series: Endocrinology ((ENDOCR))

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Abstract

Fetal development of reproductive system is a complex process which can be divided in two main stages: sex determination and sexual differentiation. During sex determination, the bipotential gonadal primordium develops – according to chromosomal sex – into either testis or ovary. Sexual differentiation subsequently involves fetal gonadal production of peptide and steroid hormones that are responsible for male or female phenotype.

This process occurs during a brief window of time and is based on sex-specific expression of transcription factors and signaling molecules that in turn drive cell fate commitment by regulating migration, proliferation, and patterning of somatic and germ cells into testis and ovary.

Pathway to maleness relies on mechanisms that have recently been shown to both promote testis development and simultaneously antagonize ovarian fate. Our understanding of these pathways has grown over the past few years, and novel players involved in sexual development, such as epigenetic regulators, have arisen.

Enlightenment of these networks is critical for a better characterization of conditions such as disorders of sex development (DSD) , infertility, and gonadal cancer.

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Abbreviations

DSD:

Disorders of Sex Development

References

  • Aaronson IA. Micropenis: medical and surgical implications. J Urol. 1994;152(1):4–14.

    Article  CAS  PubMed  Google Scholar 

  • Adams IR, McLaren A. Sexually dimorphic development of mouse primordial germ cells: switching from oogenesis to spermatogenesis. Development. 2002;129(5):1155–64.

    CAS  PubMed  Google Scholar 

  • Ansell PE, Bennett VJ, Bone DM, Bull DJ, Jackson MB, Pike LA, Chilvers CED, Dudley NE, Cough MH, Griffiths DM, Redman C, Wilkinson AR, Macfarlane A, Coupland CAC. Cryptorchidism: a prospective study of 7500 consecutive male births, 1984-8. Arch Dis Child. 1992;67(7):892–9.

    Article  Google Scholar 

  • Bagheri-Fam S, Sim H, Bernard P, Jayakody I, Taketo MM, Scherer G, Harley VR. Loss of Fgfr2 leads to partial XY sex reversal. Dev Biol. 2008;314(1):71–83.

    Article  CAS  PubMed  Google Scholar 

  • Biason-Lauber A, Konrad D, Meyer M, DeBeaufort C, Schoenle EJ. Ovaries and female phenotype in a girl with 46,XY karyotype and mutations in the CBX2 gene. Am J Hum Genet. 2009;84(5):658–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Birk OS, Casiano DE, Wassif CA, Cogliati T, Zhao L, Zhao Y, Grinberg A, Huang S, Kreidberg JA, Parker KL, Porter FD, Westphal H. The LIM homeobox gene Lhx9 is essential for mouse gonad formation. Nature. 2000;403(6772):909–13.

    Article  CAS  PubMed  Google Scholar 

  • Bott RC, Clopton DT, Fuller AM, McFee RM, Lu N, McFee RM, Cupp AS. KDR-LacZ-expressing cells are involved in ovarian and testis-specific vascular development, suggesting a role for VEGFA in the regulation of this vasculature. Cell Tissue Res. 2010;342(1):117–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bouty A, Ayers KL, Pask A, Heloury Y, Sinclair AH. The genetic and environmental factors underlying hypospadias. Sex Dev. 2015;9(5):239–59.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bowles J, Feng CW, Spiller C, Davidson TL, Jackson A, Koopman P. FGF9 suppresses meiosis and promotes male germ cell fate in mice. Dev Cell. 2010;19(3):440–9.

    Article  CAS  PubMed  Google Scholar 

  • Bredfeldt TG, Greathouse KL, Safe SH, Hung MC, Bedford MT, Walker CL. Xenoestrogen-induced regulation of EZH2 and histone methylation via estrogen receptor signaling to PI3K/AKT. Mol Endocrinol. 2010;24(5):993–1006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brennan J, Tilmann C, Capel B. Pdgfr-alpha mediates testis cord organization and fetal Leydig cell development in the XY gonad. Genes Dev. 2003;17(6):800–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bu Q, Pan Z, Jiang S, Wang A, Cheng H. The effectiveness of hCG and LHRH in boys with cryptorchidism: a meta-analysis of randomized controlled trials. Horm Metab Res. 2016;48(5):318–24.

    Article  CAS  PubMed  Google Scholar 

  • Byskov AG, Fenger M, Westergaard L, Andersen CY. Forskolin and the meiosis inducing substance synergistically initiate meiosis in fetal male germ cells. Mol Reprod Dev. 1993;34(1):47–52.

    Article  CAS  PubMed  Google Scholar 

  • Carmichael SL, Shaw GM, Lammer EJ. Environmental and genetic contributors to hypospadias: a review of the epidemiologic evidence. Birth Defects Res A Clin Mol Teratol. 2012;94:499–510.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chassot AA, Gregoire EP, Lavery R, Taketo MM, de Rooij DG, Adams IR, Chaboissier MC. RSPO1/β-catenin signaling pathway regulates oogonia differentiation and entry into meiosis in the mouse fetal ovary. PLoS One. 2011;6(10):e25641.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cho P, Cendron M. The surgical management of male epispadias in the new millennium. Curr Urol Rep. 2014;15(12):472.

    Article  PubMed  Google Scholar 

  • Chua ME, Mendoza JS, Gaston MJ, Luna Jr SL, Morales Jr ML. Hormonal therapy using gonadotropin releasing hormone for improvement of fertility index among children with cryptorchidism: a meta-analysis and systematic review. J Pediatr Surg. 2014;49(11):1659–67.

    Article  PubMed  Google Scholar 

  • 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. 2000;63(6):1825–38.

    Article  CAS  PubMed  Google Scholar 

  • Colvin JS, Green RP, Schmahl J, Capel B, Ornitz DM. Male-to-female sex reversal in mice lacking fibroblast growth factor 9. Cell. 2001;104(6):875–89.

    Article  CAS  PubMed  Google Scholar 

  • Combes AN, Wilhelm D, Davidson T, Dejana E, Harley V, Sinclair A, Koopman P. Endothelial cell migration directs testis cord formation. Dev Biol. 2009;326(1):112–20.

    Article  CAS  PubMed  Google Scholar 

  • Cook MS, Munger SC, Nadeau JH, Capel B. Regulation of male germ cell cycle arrest and differentiation by DND1 is modulated by genetic background. Development. 2011;138(1):23–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cool J, Capel B. Mixed signals: development of the testis. Semin Reprod Med. 2009;27(1):5–13.

    Article  CAS  PubMed  Google Scholar 

  • Cool J, Carmona FD, Szucsik JC, Capel B. Peritubular myoid cells are not the migrating population required for testis cord formation in the XY gonad. Sex Dev. 2008;2(3):128–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cortes D, Thorup J. Histology of testicular biopsies taken at operation for bilateral maldescended testes in relation to fertility in adulthood. Br J Urol. 1991;68(3):285–91.

    Article  CAS  PubMed  Google Scholar 

  • Cortes D, Thorup J, Visfeldt J. Hormonal treatment may harm the germ cells in 1 to 3-year-old boys with cryptorchidism. J Urol. 2000;163(4):1290–2.

    Article  CAS  PubMed  Google Scholar 

  • Cortes D, Thorup JM, Visfeldt J. Cryptorchidism: aspects of fertility and neoplasms. A study including data of 1,335 consecutive boys who underwent testicular biopsy simultaneously with surgery for cryptorchidism. Horm Res. 2001;55(1):21–7.

    CAS  PubMed  Google Scholar 

  • Cortes D, Thorup J, Lindenberg S, et al. Infertility despite surgery for cryptorchidism in childhood can be classified by patients with normal or elevated follicle-stimulating hormone and identified at orchidopexy. BJU Int. 2003;91(7):670–4.

    Article  CAS  PubMed  Google Scholar 

  • Cortes D, Holt R, de Knegt VE. Hormonal aspects of the pathogenesis and treatment of cryptorchidism. Eur J Pediatr Surg. 2016;26(5):409–17.

    Article  PubMed  Google Scholar 

  • Coughlin MT, Bellinger MF, Lee PA. Age at unilateral orchiopexy: effect on hormone levels and sperm count in adulthood. J Urol. 1999;162(3 Pt 2):986–8.

    CAS  PubMed  Google Scholar 

  • Cupp AS, Kim GH, Skinner MK. Expression and action of neurotropin-3 and nerve growth factor in embryonic and early postnatal rat testis development. Biol Reprod. 2000;63(6):1617–28.

    Article  CAS  PubMed  Google Scholar 

  • Cupp AS, Uzumcu M, Skinner MK. Chemotactic role of neurotropin 3 in the embryonic testis that facilitates male sex determination. Biol Reprod. 2003;68(6):2033–7.

    Article  CAS  PubMed  Google Scholar 

  • Domenice S, Latronico AC, Brito VN, Arnhold IJ, Kok F, Mendonca BB. Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene. J Clin Endocrinol Metab. 2001;86(9):4068–71.

    Article  CAS  PubMed  Google Scholar 

  • Durairajanayagam D, Agarwal A, Ong C. Causes, effects and molecular mechanisms of testicular heat stress. Reprod BioMed Online. 2015;30(1):14–27.

    Article  CAS  PubMed  Google Scholar 

  • Elder JS. Ultrasonography is unnecessary in evaluating boys with a nonpalpable testis. Pediatrics. 2002;110(4):748–51.

    Article  PubMed  Google Scholar 

  • Engeler DS, Hösli PO, John H, Bannwart F, Sulser T, Amin MB, Heitz PU, Hailemariam S. Early orchiopexy: prepubertal intratubular germ cell neoplasia and fertility outcome. Urology. 2000;56(1):144–8.

    Article  CAS  PubMed  Google Scholar 

  • Ferguson L, Agoulnik AI. Testicular cancer and cryptorchidism. Front Endocrinol. 2013;4:32.

    Article  Google Scholar 

  • Ferrara N, Carver-Moore K, Chen H, Dowd M, Lu L, O’Shea KS, Powell-Braxton L, Hillan KJ, Moore MW. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature. 1996;380(6573):439–42.

    Article  CAS  PubMed  Google Scholar 

  • Frimberger D. Diagnosis and management of epispadias. Semin Pediatr Surg. 2011;20(2):85–90.

    Article  PubMed  Google Scholar 

  • Giannopoulos MF, Vlachakis IG, Charissis GC. 13 years’ experience with the combined hormonal therapy of cryptorchidism. Horm Res. 2001;55(1):33–7.

    CAS  PubMed  Google Scholar 

  • Gnessi L, Basciani S, Mariani S, Arizzi M, Spera G, Wang C, Bondjers C, Karlsson L, Betsholtz C. Leydig cell loss and spermatogenic arrest in platelet-derived growth factor (PDGF)-A-deficient mice. J Cell Biol. 2000;149(5):1019–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hadziselimovic F. Successful treatment of unilateral cryptorchid boys risking infertility with LH-RH analogue. Int Braz J Urol. 2008;34(3):319–26.

    Article  PubMed  Google Scholar 

  • Hadziselimovic F, Herzog B. Treatment with a luteinizing hormone-releasing hormone analogue after successful orchiopexy markedly improves the chance of fertility later in life. J Urol. 1997;158(3 Pt 2):1193–5.

    Article  CAS  PubMed  Google Scholar 

  • Hadziselimovic F, Herzog B, Seguchi H. Surgical correction of cryptorchism at 2 years: electron microscopic and morphometric investigations. J Pediatr Surg. 1975;10(1):19–26.

    Article  CAS  PubMed  Google Scholar 

  • 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. 1996;1(7):663–71.

    Article  CAS  PubMed  Google Scholar 

  • Hatipoğlu N, Kurtoğlu S. Micropenis: etiology, diagnosis and treatment approaches. J Clin Res Pediatr Endocrinol. 2013;5(4):217–23

    Google Scholar 

  • Henna MR, Del Nero RG, Sampaio CZ, et al. Hormonal cryptorchidism therapy: systematic review with meta-analysis of randomized clinical trials. Pediatr Surg Int. 2004;20(5):357–9.

    Article  PubMed  Google Scholar 

  • Hiramatsu R, Matoba S, Kanai-Azuma M, Tsunekawa N, Katoh-Fukui Y, Kurohmaru M, Morohashi K, Wilhelm D, Koopman P, Kanai Y. A critical time window of SRY action in gonadal sex determination in mice. Development. 2009;136(1):129–38.

    Article  CAS  PubMed  Google Scholar 

  • Hoy NY, Rourke KF. Better defining the spectrum of adult hypospadias: examining the effect of childhood surgery on adult presentation. Urology. 2017;99:281–6.

    Article  PubMed  Google Scholar 

  • Huff DS, Fenig DM, Canning DA, Carr MG, Zderic SA, Snyder 3rd HM. Abnormal germ cell development in cryptorchidism. Horm Res. 2001;55(1):11–7.

    CAS  PubMed  Google Scholar 

  • Hughes IA, Houk C, Ahmed SF, Lee PA. Lawson Wilkins Pediatric Endocrine Society/European Society for Paediatric Endocrinology Consensus Group: consensus statement on management of intersex disorders. J Pediatr Urol. 2006;2:148–62.

    Article  CAS  PubMed  Google Scholar 

  • Hutson JM, Hasthorpe S. Testicular descent and cryptorchidism: the state of the art in 2004. J Pediatr Surg. 2005;40(2):297–302.

    Article  PubMed  Google Scholar 

  • Kalfa N, Philibert P, Sultan C. Is hypospadias a genetic, endocrine or environmental disease, or still an unexplained malformation? Int J Androl. 2009;32(3):187–97.

    Article  CAS  PubMed  Google Scholar 

  • Katoh-Fukui Y, Miyabayashi K, Komatsu T, Owaki A, Baba T, Shima Y, Kidokoro T, Kanai Y, Schedl A, Wilhelm D, Koopman P, Okuno Y, Morohashi K. Cbx2, a polycomb group gene, is required for SRY gene expression in mice. Endocrinology. 2012;153(2):913–24.

    Article  CAS  PubMed  Google Scholar 

  • Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier MC, Poulat F, Behringer RR, Lovell-Badge R, Capel B. FGF9 and WNT4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol. 2006;4(6):e187.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kitamura K, Yanazawa M, Sugiyama N, Miura H, Iizuka-Kogo A, Kusaka M, Omichi K, Suzuki R, Kato-Fukui Y, Kamiirisa K, Matsuo M, Kamijo S, Kasahara M, Yoshioka H, Ogata T, Fukuda T, Kondo I, Kato M, Dobyns WB, Yokoyama M, Morohashi K. Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans. Nat Genet. 2002;32(3):359–69.

    Article  CAS  PubMed  Google Scholar 

  • Kocer A, Reichmann J, Best D, Adams IR. Germ cell sex determination in mammals. Mol Hum Reprod. 2009;15(4):205–13

    Google Scholar 

  • Köhler B, Achermann JC. Update–steroidogenic factor 1 (SF-1, NR5A1). Minerva Endocrinol. 2010;35(2):73–86.

    PubMed  Google Scholar 

  • Köhler B, Biebermann H, Friedsam V, Gellermann J, Maier RF, Pohl M, Wieacker P, Hiort O, Grüters A, Krude H. Analysis of the Wilms’ tumor suppressor gene (WT1) in patients 46,XY disorders of sex development. J Clin Endocrinol Metab. 2011;96(7):E1131–6.

    Article  PubMed  Google Scholar 

  • Kolasa A, Misiakiewicz K, Marchlewicz M, Wiszniewska B. The generation of spermatogonial stem cells and spermatogonia in mammals. Reprod Biol. 2012;12(1):5–23.

    Article  PubMed  Google Scholar 

  • Kolon TF, Herndon CDA, Baker LA, et al. American Urological Assocation. Evaluation and treatment of cryptorchidism: AUA guideline. J Urol. 2014;192(2):337–45.

    Article  PubMed  Google Scholar 

  • Kraft KH, Shukla AR, Canning DA. Hypospadias. Urol Clin North Am. 2010;37(2):167–81.

    Article  PubMed  Google Scholar 

  • Kraft KH, Canning DA, Snyder 3rd HM, Kolon TF. Undescended testis histology correlation with adult hormone levels and semen analysis. J Urol. 2012;188:1429e35.

    Article  CAS  Google Scholar 

  • Kramer SA, Kelalis PP. Assessment of urinary continence in epispadias: review of 94 patients. J Urol. 1982;128(2):290–3.

    Article  CAS  PubMed  Google Scholar 

  • Kremer H, Kraaij R, Toledo SP, Post M, Fridman JB, Hayashida CY, van Reen M, Milgrom E, Ropers HH, Mariman E. Male pseudohermaphroditism due to a homozygous missense mutation of the luteinizing hormone receptor gene. Nat Genet. 1995;9(2):160–4.

    Article  CAS  PubMed  Google Scholar 

  • Lala R, Matarazzo P, Chiabotto P, de Sanctis C, Canavese F, Hadziselimovic F. Combined therapy with LHRH and HCG in cryptorchid infants. Eur J Pediatr. 1993;152(Suppl. 2):S31e3.

    Google Scholar 

  • Lee PA. Fertility after cryptorchidism: epidemiology and other outcome studies. Urology. 2005;66(2):427–31.

    Article  PubMed  Google Scholar 

  • Lin YT, Capel B. Cell fate commitment during mammalian sex determination. Curr Opin Genet Dev. 2015;32:144–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loftin CD, Tiano HF, Langenbach R. Phenotypes of the COX-deficient mice indicate physiological and pathophysiological roles for COX-1 and COX-2. Prostaglandins Other Lipid Mediat. 2002;68–69:177–85.

    Google Scholar 

  • Lu N, Sargent KM, Clopton DT, Pohlmeier WE, Brauer VM, McFee RM, Weber JS, Ferrara N, Silversides DW, Cupp AS. Loss of vascular endothelial growth factor A (VEGFA) isoforms in the testes of male mice causes subfertility, reduces sperm numbers, and alters expression of genes that regulate undifferentiated spermatogonia. Endocrinology. 2013;154(12):4790–802.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ludwig G, Potempa J. Optimal time for treating cryptorchism. Dtsch Med Wochenschr. 1975;100(13):680–3.

    Article  CAS  PubMed  Google Scholar 

  • MacLean G, Li H, Metzger D, Chambon P, Petkovich M. Apoptotic extinction of germ cells in testes of Cyp26b1 knockout mice. Endocrinology. 2007;148(10):4560–7.

    Article  CAS  PubMed  Google Scholar 

  • Mandat KM, Wieczorkiewicz B, Gubała-Kacała M, Sypniewski J, Bujok G. Semen analysis of patients who had orchidopexy in childhood. Eur J Pediatr Surg. 1994;4(2):94–7.

    Article  CAS  PubMed  Google Scholar 

  • Manzoni G, Bracka A, Palminteri E, Marrocco G. Hypospadias surgery: when, what and by whom? BJU Int. 2004;94(8):1188–95.

    Article  PubMed  Google Scholar 

  • Mayr J, Pusch HH, Schimpl G, Reitinger T, Sorantin E, Mayr-Koci M. Semen quality and gonadotropin levels in patients operated upon for cryptorchidism. Pediatr Surg Int. 1996;11(5–6):354–8.

    Article  CAS  PubMed  Google Scholar 

  • McAleer IM, Packer MG, Kaplan GW, Scherz HC, Krous HF, Billman GF. Fertility index analysis in cryptorchidism. J Urol. 1995;153(4):1255–8.

    Article  CAS  PubMed  Google Scholar 

  • McLaren A, Southee D. Entry of mouse embryonic germ cells into meiosis. Dev Biol. 1997;187(1):107–13.

    Article  CAS  PubMed  Google Scholar 

  • Mehendale VG, Shenoy SN, Shah RS, Chaudhari NC, Mehendale AV. Laparoscopic management of impalpable undescended testes: 20 years’ experience. J Minim Access Surg. 2013;9(4):149–53.

    Article  PubMed  PubMed Central  Google Scholar 

  • Møller H, Prener A, Skakkebaek NE. Testicular cancer, cryptorchidism, inguinal hernia, testicular atrophy, and genital malformations: case-control studies in Denmark. Cancer Causes Control. 1996;7(2):264–74.

    Article  PubMed  Google Scholar 

  • Morita Y, Tilly JL. Segregation of retinoic acid effects on fetal ovarian germ cell mitosis versus apoptosis by requirement for new macromolecular synthesis. Endocrinology. 1999;140(6):2696–703.

    Article  CAS  PubMed  Google Scholar 

  • Munger SC, Natarajan A, Looger LL, Ohler U, Capel B. Fine time course expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination. PLoS Genet. 2013;9(7):e1003630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murphy F, Paran TS, Puri P. Orchidopexy and its impact on fertility. Pediatr Surg Int. 2007;23(7):625–32.

    Article  PubMed  Google Scholar 

  • Nelson CP, Park JM, Wan J, Bloom DA, Dunn RL, Wei JT. The increasing incidence of congenital penile anomalies in the United States. J Urol. 2005;174:1573–6.

    Article  PubMed  Google Scholar 

  • Nel-Themaat L, Vadakkan TJ, Wang Y, Dickinson ME, Akiyama H, Behringer RR. Morphometric analysis of testis cord formation in SOX9-EGFP mice. Dev Dyn. 2009;238(5):1100–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nel-Themaat L, Jang CW, Stewart MD, Akiyama H, Viger RS, Behringer RR. Sertoli cell behaviors in developing testis cords and postnatal seminiferous tubules of the mouse. Biol Reprod. 2011;84(2):342–50.

    Article  CAS  PubMed  Google Scholar 

  • O’Shaughnessy PJ, Baker PJ, Johnston H. Neuroendocrine regulation of Leydig cell development. Ann N Y Acad Sci. 2005;1061:109–19.

    Article  PubMed  CAS  Google Scholar 

  • O’Shaughnessy PJ, Baker PJ, Johnston H. The foetal Leydig cell – differentiation, function and regulation. Int J Androl. 2006;29(1):90–5. discussion 105-8.

    Article  PubMed  CAS  Google Scholar 

  • Penson D, Krishnaswami S, Jules A, McPheeters ML. Effectiveness of hormonal and surgical therapies for cryptorchidism: a systematic review. Pediatrics. 2013;131(6):e1897–907.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pettersson A, Richiardi L, Nordenskjold A, Kaijser M, Akre O. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med. 2007;356(18):1835–41.

    Article  CAS  PubMed  Google Scholar 

  • Piard J, Mignot B, Arbez-Gindre F, Aubert D, Morel Y, Roze V, McElreavy K, Jonveaux P, Valduga M, Van Maldergem L. Severe sex differentiation disorder in a boy with a 3.8 Mb 10q25.3-q26.12 microdeletion encompassing EMX2. Am J Med Genet A. 2014;164A(10):2618–22.

    Article  PubMed  CAS  Google Scholar 

  • Puri P, Sparnon A. Relationship of primary site of testis to final testicular size in cryptorchid patients. Br J Urol. 1990;66(2):208–10.

    Article  CAS  PubMed  Google Scholar 

  • Radmayr C, Dogan HS, Hoebeke P, Kocvara R, Nijman R, Stein R, Undre S, Tekgul S. Management of undescended testes: European Association of Urology/European Society for Paediatric Urology Guidelines. J Pediatr Urol. 2016;12:335e343.

    Article  Google Scholar 

  • Rajfer J, Handelsman DJ, Swerdloff RS, Hurwitz R, Kaplan H, Vandergast T, et al. Hormonal therapy of cryptorchidism. A randomized, double-blind study comparing human chorionic gonadotropin and gonadotropin-releasing hormone. New Engl J Med. 1986;314:466e70.

    Article  Google Scholar 

  • Rey RA, Codner E, Iñíguez G, Bedecarrás P, Trigo R, Okuma C, Gottlieb S, Bergadá I, Campo SM, Cassorla FG. Low risk of impaired testicular Sertoli and Leydig cell functions in boys with isolated hypospadias. J Clin Endocrinol Metab. 2005;90(11):6035–40.

    Article  CAS  PubMed  Google Scholar 

  • Ritzén EM, Bergh A, Bjerknes R, et al. Nordic consensus on treatment of undescended testes. Acta Paediatr. 2007;96(5):638–43.

    Article  PubMed  Google Scholar 

  • Ságodi L, Kiss A, Kiss-Tóth E, Barkai L. Prevalence and possible causes of hypospadias (in Hungarian). Orv Hetil. 2014;155:978–85.

    Article  PubMed  Google Scholar 

  • Sargent KM, McFee RM, Spuri Gomes R, Cupp AS. Vascular endothelial growth factor A: just one of multiple mechanisms for sex-specific vascular development within the testis? J Endocrinol. 2015;227(2):R31–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmahl J, Eicher EM, Washburn LL, Capel B. SRY induces cell proliferation in the mouse gonad. Development. 2000;127(1):65–73.

    CAS  PubMed  Google Scholar 

  • Schmahl J, Kim Y, Colvin JS, Ornitz DM, Capel B. FGF9 induces proliferation and nuclear localization of FGFR2 in Sertoli precursors during male sex determination. Development. 2004;131(15):3627–36.

    Article  CAS  PubMed  Google Scholar 

  • Schreiber K, Menardi G, Marberger H, et al. Late results after surgical treatment of maldescended testes with special regard to exocrine and endocrine testicular function. Eur Urol. 1981;7:268–73.

    Article  Google Scholar 

  • Skakkebaek NE, Rajpert-De Meyts E, Buck Louis GM, Toppari J, Andersson AM, Eisenberg ML, Jensen TK, Jørgensen N, Swan SH, Sapra KJ, Ziebe S, Priskorn L, Juul A. Male reproductive disorders and fertility trends: influences of environment and genetic susceptibility. Physiol Rev. 2016;96(1):55–97.

    Article  CAS  PubMed  Google Scholar 

  • Springer A, Krois W, Horcher E. Trends in hypospadias surgery: results of a worldwide survey. Eur Urol. 2011;60:1184e9.

    Google Scholar 

  • Springer A, van den Heijkant M, Baumann S. Worldwide prevalence of hypospadias. J Pediatr Urol. 2016;12(3):152.e1–7.

    Article  CAS  Google Scholar 

  • Stedman F, Bradshaw CJ, Kufeji D. Current practice and outcomes in the management of intra-abdominal testes. Eur J Pediatr Surg. 2015;25(5):409–13.

    PubMed  Google Scholar 

  • Suzuki A, Niimi Y, Saga Y. Interaction of NANOS2 and NANOS3 with different components of the CNOT complex may contribute to the functional differences in mouse male germ cells. Biol Open. 2014;3(12):1207–16.

    Article  PubMed  PubMed Central  Google Scholar 

  • Svingen T, Koopman P. Building the mammalian testis: origins, differentiation, and assembly of the component cell populations. Genes Dev. 2013;27(22):2409–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang H, Brennan J, Karl J, Hamada Y, Raetzman L, Capel B. Notch signaling maintains Leydig progenitor cells in the mouse testis. Development. 2008;135(22):3745–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teerds KJ, Huhtaniemi IT. Morphological and functional maturation of Leydig cells: from rodent models to primates. Hum Reprod Update. 2015;21(3):310–28.

    Article  PubMed  Google Scholar 

  • Thorup J, McLachlan R, Cortes D, Nation TR, Balic A, Southwell BR, Hutson JM. What is new in cryptorchidism and hypospadias – a critical review on the testicular dysgenesis hypothesis. J Pediatr Surg. 2010;45(10):2074–86.

    Article  PubMed  Google Scholar 

  • Thorup J, Clasen-Linde E, Thorup SC, et al. Pre- and postoperative status of gonadotropins (FSH and LH) and inhibin B in relation to testicular histopathology at orchidopexy in infant boys with unilateral undescended testes. J Pediatr Urol. 2015;11(1):25.e1–5.

    Article  Google Scholar 

  • Virtanen HE, Toppari J. Cryptorchidism and fertility. Endocrinol Metab Clin North Am. 2015;44(4):751–60.

    Article  PubMed  Google Scholar 

  • Wilhelm D, Martinson F, Bradford S, Wilson MJ, Combes AN, Beverdam A, Bowles J, Mizusaki H, Koopman P. Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signaling during mammalian sex determination. Dev Biol. 2005;287(1):111–24.

    Article  CAS  PubMed  Google Scholar 

  • Wilson-Storey D, McGenity K, Dickson JA. Orchidopexy: the younger the better? J R Coll Surg Edinb. 1990;35(6):362–4.

    CAS  PubMed  Google Scholar 

  • Wong RL, Walker CL. Molecular pathways: environmental estrogens activate nongenomic signaling to developmentally reprogram the epigenome. Clin Cancer Res. 2013;19(14):3732–7.

    Article  CAS  PubMed  Google Scholar 

  • Wood D, Woodhouse C. Penile anomalies in adolescence. ScientificWorldJournal. 2011;11:614–23.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yao HH, Whoriskey W, Capel B. Desert Hedgehog/Patched 1 signaling specifies fetal Leydig cell fate in testis organogenesis. Genes Dev. 2002;16(11):1433–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Istituto Giannina Gaslini, University of Genova, Largo Gaslini 5, 16147, Genova, Italy

    Girolamo Mattioli & Irene Paraboschi

  2. Department of Pediatrics, Istituto Giannina Gaslini, University of Genova, Largo Gaslini 5, 16147, Genova, Italy

    Pietro Lazzeroni, Natascia Di Iorgi, Flavia Napoli & Mohamad Maghnie

Authors
  1. Girolamo Mattioli
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  2. Pietro Lazzeroni
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  3. Irene Paraboschi
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  4. Natascia Di Iorgi
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  5. Flavia Napoli
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  6. Mohamad Maghnie
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Corresponding author

Correspondence to Mohamad Maghnie .

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Editors and Affiliations

  1. Unit of Endocrinology Department of Biomedical Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy

    Manuela Simoni

  2. Faculty of Medicine Department of Surgery and Cancer, Imperial College London, London, United Kingdom

    Ilpo T. Huhtaniemi

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Mattioli, G., Lazzeroni, P., Paraboschi, I., Di Iorgi, N., Napoli, F., Maghnie, M. (2017). Testis Development and Descent. In: Simoni, M., Huhtaniemi, I. (eds) Endocrinology of the Testis and Male Reproduction. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-44441-3_8

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  • DOI: https://doi.org/10.1007/978-3-319-44441-3_8

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-44440-6

  • Online ISBN: 978-3-319-44441-3

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