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2 - Molecular genetics of gonad development

from Part I - Normal development

Published online by Cambridge University Press:  04 May 2010

By
Andrew Sinclair  and
Fergus Cameron
Edited by
Adam H. Balen ,
Sarah M. Creighton ,
Melanie C. Davies ,
Jane MacDougall  and
Richard Stanhope
Andrew Sinclair
Affiliation:
Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia
Fergus Cameron
Affiliation:
Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia
Adam H. Balen
Affiliation:
Leeds Teaching Hospitals, University Trust
Sarah M. Creighton
Affiliation:
University College London Hospitals
Melanie C. Davies
Affiliation:
University College London
Jane MacDougall
Affiliation:
Addenbrooke's Hospital, Cambridge
Richard Stanhope
Affiliation:
Great Ormond Street Hospital
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Summary

Introduction

Sex determination involves the commitment of the embryo to follow either a male or female developmental pathway. The key step in this process is the development of the undifferentiated embryonic gonads into either testes or ovaries. In humans, sex is determined at the moment of fertilization by the constitution of the sex chromosomes. Two X chromosomes result in ovaries and a female phenotype while an X and Y constitution produces testes and male development.

It has been known for some time that the Y chromosome carries a dominant testis-determining gene, which causes the undifferentiated embryonic gonad to develop as a testis. The masculinizing effect of the testis results from the secretion of the hormones testosterone and anti-Müllerian hormone (AMH; also known as Müllerian inhibitory substance, MIS). AMH causes regression of the embryonic female Müllerian ducts. In the absence of the Y chromosome (and absence of the testis-determining gene), ovaries will develop. Interestingly, female development will still occur in the absence of ovaries or their hormonal products. Consequently, the decisive event in sex determination is whether or not a testis develops. In humans and other mammals, sex determination can be equated with testis determination.

This chapter describes what we know of the genes that control human gonad development and how alterations in these genes can cause sex-reversed phenotypes. The Y-linked testis-determining gene SRY and others in this complex developmental network, such as SOX9, WT1, SF1, DAX1 and DMRT1, are discussed.

Type
Chapter
Information
Paediatric and Adolescent Gynaecology
A Multidisciplinary Approach
 , pp. 9 - 21
Publisher: Cambridge University Press
Print publication year: 2004

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