A molecular basis for estrogen-induced cryptorchidism.
Male sexual differentiation relies upon testicular secretion of the hormones testosterone, Mullerian inhibiting substance, and insulin-3 (Insl3). Insl3 is responsible for testicular descent through virilization and outgrowth of the embryonic gubernaculum. In mouse, prenatal exposure to 17beta-estradiol and the nonsteroidal synthetic estrogen diethylstilbestrol (DES) disturbs the endocrine balance, causing demasculinizing and feminizing effects in the male embryo, including impaired testicular descent (cryptorchidism). In the current study, we show that maternal exposure to estrogens, including 17alpha- and beta-estradiol, as well as DES, specifically down regulates Insl3 expression in embryonic Leydig cells, thereby providing a mechanism for cryptorchidism. These experiments may have implications for the widespread use of estrogenic substances in agriculture and the environment.
Center for Developmental Biology, University of Texas, Southwestern Medical Center, Dallas 75390-9133, USA.
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D000818:Animals; D003456:Cryptorchidism / Q000139:chemically induced*; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007328:Insulin; D008297:Male; D051379:Mice; D008855:Microscopy, Electron, Scanning; D011247:Pregnancy; D011506:Proteins / Q000235:genetics; D013737:Testis / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D014158:Transcription, Genetic / Q000187:drug effects
D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; D004958:Estradiol