title: Genetic mechanisms of fetal male undermasculinization: a background to the role of endocrine disruptors.
abstract: Fetal male sex development proceeds along an orderly sequence of events coordinated by an interplay of genetic and hormonal events. These operate in a time- and concentration-dependent manner. Once a testis is formed (the female sex being constitutive in nature), differentiation of the internal and external male genitalia is androgen dependent. A number of genetic syndromes of sex reversal are well characterized at the biochemical and molecular levels. They fall into three principal categories: defects in formation of the testis, defects in production of androgens, and defects in the action of androgens. In many instances, the precise cause is not established, although the investigative evidence points in the direction of one of the three stated classifications. Polymorphic variants in several of the genes involved in male development are associated with certain degrees of male undermasculinization. While the genetic background is essentially static, it is plausible that the effect of endocrine disruptors during fetal life acting through epigenetic mechanisms may partly explain the observed changing trends in male reproductive tract disorders.
authors.affiliation: Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Box 116, Level 8, Hills Road, Cambridge CB2 2QQ, UK. iah1000@cam.ac.uk
authors.forename: Ieuan A
authors.initials: IA
authors.lastname: Hughes
authors.forename: Howard
authors.initials: H
authors.lastname: Martin
authors.forename: Jarmo
authors.initials: J
authors.lastname: Jääskeläinen
mesh_terms: D000818:Animals; D012734:Disorders of Sex Development / Q000196:embryology* / Q000235:genetics; D047108:Embryonic Development / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005837:Genitalia, Male / Q000187:drug effects / Q000196:embryology; D006801:Humans; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D019849:Sex Determination Processes; D012733:Sex Differentiation / Q000187:drug effects
chemical_list: D052244:Endocrine Disruptors