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The Molecular Genetics of Testis Determination

  • Neha Singh
  • Deepak ModiEmail author
Chapter
  • 35 Downloads

Abstract

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.

Keywords

Gonads SRY gene Mullerian ducts Sertoli cell Sex differentiation Testis 

Abbreviations

ALCs

Adult Leydig cells

AMH

Anti-Mullerian hormone

ATRX

Alpha thalassemia/mental retardation syndrome

BPES

Blepharophimosis/ptosis/epicanthus inversus syndrome

CAH

Congenital adrenal hypoplasia

CBX2

Chromobox homolog 2

CGD

Complete gonadal dysgenesis

CYP26B1

Cytochrome P450, family 26, subfamily b, polypeptide 1

DAX1

DSS AHC critical region on the chromosome X

DAZL

Deleted in azoospermia-like

DDX4

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

DHH

Desert hedgehog

DMRT1

dsx- and mab3-related transcription factor 1

DSD

Disorders of sex development

E

Embryonic day

EMX2

Empty spiracles homeobox 2

FGFR2

FGF receptor 2

FLCs

Fetal Leydig cells

FOG2

Friend of GATA-2

FOXL2

Forkhead box L2

GADD45G

Growth arrest and DNA damage-inducible 45 G

GATA4

GATA binding protein 4

GD

Gonadal dysgenesis

HMG

High-mobility group

LHX9

LIM homeobox 9

LOF

Loss of function

NR0B1

Nuclear receptor subfamily 0, group B, gene 1

NR5A1/SF1

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

PGCs

Primordial germ cells

PGD

Partial gonadal dysgenesis

PMCS

Peritubular myoid cells

PTCH1

Patched receptor 1

RSPO1

R-spondin family 1

SIX1/4

SIX homeobox 1/4

SOX

Sry-related HMG box

SOX10

Sry-related HMG box 10

SOX9

Sry-related HMG box 9

SRY

Sex-determining region on Y chromosome

WES

Whole exome sequencing

WNT4

Wingless-type MMTV integration site family, member 4

WT1

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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