The Molecular Genetics of Testis Determination

  • Neha Singh
  • Deepak ModiEmail author


Testis development involves the initial specification of Sertoli cells by expression of SRY-SOX9-FGF9 cascade that triggers organization of seminiferous tubules, differentiation of Leydig and peritubular myoid cells, and finally vascularization. At the same time, germ cells inhibit meiosis by the virtue of Sertoli cells degrading retinoic acid and entering spermatogonia fate. Decision of the bipotential gonad to form the testis is however not irreversible and requires maintenance by DMRT1. In absence of the key genetic players involved in Sertoli cell development and maintenance, the gonad can be compromised, and the cells can take an alternate (ovarian) fate. While the picture of the genetic network required for testis development and sex differentiation is clear, we are unable to explain the etiology of DSD in most of the cases. A better understanding of the players involved in the process of testis differentiation is required for evolving strategies for diagnosis and management of DSDs.


Gonads SRY gene Mullerian ducts Sertoli cell Sex differentiation Testis 



Adult Leydig cells


Anti-Mullerian hormone


Alpha thalassemia/mental retardation syndrome


Blepharophimosis/ptosis/epicanthus inversus syndrome


Congenital adrenal hypoplasia


Chromobox homolog 2


Complete gonadal dysgenesis


Cytochrome P450, family 26, subfamily b, polypeptide 1


DSS AHC critical region on the chromosome X


Deleted in azoospermia-like


DEAD (Asp-Glu-Ala-Asp) box polypeptide 4


Desert hedgehog


dsx- and mab3-related transcription factor 1


Disorders of sex development


Embryonic day


Empty spiracles homeobox 2


FGF receptor 2


Fetal Leydig cells


Friend of GATA-2


Forkhead box L2


Growth arrest and DNA damage-inducible 45 G


GATA binding protein 4


Gonadal dysgenesis


High-mobility group


LIM homeobox 9


Loss of function


Nuclear receptor subfamily 0, group B, gene 1


Nuclear receptor subfamily 5, group A, gene 1/steroidogenic factor 1


Primordial germ cells


Partial gonadal dysgenesis


Peritubular myoid cells


Patched receptor 1


R-spondin family 1


SIX homeobox 1/4


Sry-related HMG box


Sry-related HMG box 10


Sry-related HMG box 9


Sex-determining region on Y chromosome


Whole exome sequencing


Wingless-type MMTV integration site family, member 4


Wilms’ tumor 1


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Molecular and Cellular Biology LaboratoryNational Institute for Research in Reproductive Health – Indian Council of Medical ResearchMumbaiIndia

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