title: Developmental changes in testicular sensitivity to estrogens throughout fetal and neonatal life.
abstract: There is now compelling evidence that inappropriate exposure to estrogen during fetal or neonatal life could affect adult reproductive functions because the testis is sensitive to estrogens during specific periods of its development. Therefore, we investigated the effects of exogenous estrogens on gametogenesis and steroidogenesis during fetal and neonatal testicular development in the rat. We used in vitro systems, organ cultures, and dispersed testicular cell cultures, which allow the development of fetal and neonatal germ cells (gonocytes) and Leydig cells. Exogenous estrogens inhibited testosterone production in dispersed testicular cell cultures throughout fetal life, but this inhibition was observed only in the early fetal stages in organ culture. By using an aromatase inhibitor (letrozole, Novartis Pharma AG), we showed that the inhibitory effect of exogenous estrogens on testosterone production is masked in the whole testis at later stages (20.5 days postconception) due essentially to local production of estrogens. In both systems, additions of high concentrations (10(-6) M) of 17beta-estradiol or diethylstilbestrol decreased the number of gonocytes during the first fetal proliferative period but not during the neonatal period. Letrozole was without effect, suggesting that the aging-related loss of responsiveness of gonocytes is not due to any aromatase activity in the gonocytes.
authors.affiliation: Laboratory of Differentiation and Radiobiology of the Gonads, Université Paris 7-Denis Diderot and CEA, DSV/iRCM/SCSR/LDRG and INSERM, Unité 566, F-92265, Fontenay aux Roses, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Delbès
authors.forename: Clotilde
authors.initials: C
authors.lastname: Duquenne
authors.forename: Jessica
authors.initials: J
authors.lastname: Szenker
authors.forename: Julie
authors.initials: J
authors.lastname: Taccoen
authors.forename: René
authors.initials: R
authors.lastname: Habert
authors.forename: Christine
authors.initials: C
authors.lastname: Levacher
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D047072:Aromatase Inhibitors / Q000494:pharmacology; D002452:Cell Count; D002478:Cells, Cultured; D004054:Diethylstilbestrol / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000633:toxicity*; D047109:Fetal Development / Q000187:drug effects*; D005865:Gestational Age; D000077289:Letrozole; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D009924:Organ Culture Techniques; D038081:Organogenesis / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D004958:Estradiol; D004054:Diethylstilbestrol; D000077289:Letrozole