Pathways of endocrine disruption during male sexual differentiation and masculinization.
After testis formation, further development of a male phenotype (masculinization) is driven by three hormones from the foetal testis: anti-Müllerian hormone, insulin-like factor 3, and testosterone. These hormones divert the development of reproductive and other organs from female to male and also play a role in testis development. The hormone dependence of masculinization renders this process inherently susceptible to disruption by factors that interfere with hormone production, bioavailability, metabolism, or action. This susceptibility is illustrated by the high prevalence of congenital masculinization disorders (cryptorchidism, hypospadias) and disorders in young adult men (low sperm counts, testis cancer), which may also stem from maldevelopment (dysgenesis) of the foetal testis. Testicular dysgenesis occurring in humans, or which is induced in animal models by foetal exposure to certain phthalates, is associated with impaired hormone production by the foetal testis. There is currently no definitive evidence that exposure of humans to environmental chemicals can induce testicular dysgenesis and/or impair masculinization, though pathways via which this could potentially occur are established.
Sharpe
Richard M
RM
MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. r.sharpe@hrsu.mrc.ac.uk
D000818:Animals; D054304:Anti-Mullerian Hormone; D052244:Endocrine Disruptors / Q000633:toxicity*; D004702:Endocrine Glands / Q000187:drug effects*; D006023:Glycoproteins / Q000502:physiology; D006059:Gonadal Dysgenesis / Q000139:chemically induced*; D006801:Humans; D007328:Insulin / Q000502:physiology; D008297:Male; D011506:Proteins / Q000502:physiology; D011944:Receptors, Androgen / Q000187:drug effects; D011960:Receptors, Estrogen / Q000187:drug effects; D019849:Sex Determination Processes; D012733:Sex Differentiation / Q000187:drug effects*; D012738:Sex Hormone-Binding Globulin / Q000096:biosynthesis; D013735:Testicular Hormones / Q000502:physiology; D013737:Testis / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D013739:Testosterone / Q000502:physiology
D052244:Endocrine Disruptors; D006023:Glycoproteins; D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D012738:Sex Hormone-Binding Globulin; D013735:Testicular Hormones; D013739:Testosterone; D054304:Anti-Mullerian Hormone