The molecular and cellular basis of gonadal sex reversal in mice and humans

Wiley Interdiscip Rev Dev Biol. 2012 Jul-Aug;1(4):559-77. doi: 10.1002/wdev.42. Epub 2012 Feb 28.

Abstract

The mammalian gonad is adapted for the production of germ cells and is an endocrine gland that controls sexual maturation and fertility. Gonadal sex reversal, namely, the development of ovaries in an XY individual or testes in an XX, has fascinated biologists for decades. The phenomenon suggests the existence of genetic suppressors of the male and female developmental pathways and molecular genetic studies, particularly in the mouse, have revealed controlled antagonism at the core of mammalian sex determination. Both testis and ovary determination represent design solutions to a number of problems: how to generate cells with the right properties to populate the organ primordium; how to produce distinct organs from an initially bipotential primordium; how to pattern an organ when the expression of key cell fate determinants is initiated only in a discrete region of the primordium and extends to other regions asynchronously; how to coordinate the interaction between distinct cell types in time and space and stabilize the resulting morphology; and how to maintain the differentiated state of the organ throughout the adult period. Some of these, and related problems, are common to organogenesis in general; some are distinctive to gonad development. In this review, we discuss recent studies of the molecular and cellular events underlying testis and ovary development, with an emphasis on the phenomenon of gonadal sex reversal and its causes in mice and humans. Finally, we discuss sex-determining loci and disorders of sex development in humans and the future of research in this important area.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Lineage
  • Disorders of Sex Development / genetics
  • Disorders of Sex Development / metabolism*
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Gonads / cytology
  • Gonads / embryology
  • Gonads / growth & development
  • Humans
  • Male
  • Mice
  • Sex Determination Processes / genetics*