ToxSci Advance Access published online on June 14, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm160
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Developmental Changes in Testicular Sensitivity to Estrogens Throughout Fetal and Neonatal life
1 Laboratory of Differentiation and Radiobiology of the Gonads, Unit of Gametogenesis and Genotoxicity, Unité Mixte de Recherche-S 566, Université Denis Diderot-Paris 7, F-92265, Fontenay aux Roses, France; CEA, DSV/IRCM/SCSR/LDRG, F-92265, Fontenay aux Roses, France; INSERM, Unité 566, F-92265, Fontenay aux Roses, France
Correspondence: Dr Christine LEVACHER, LDRG/SCSR/IRCM /DSV, Centre CEA, BP6, F-92265, Fontenay aux Roses, France, Tel: 33 1 46 54 99 12, Fax: 33 1 46 54 99 06, E-mail: christine.levacher{at}cea.fr
Received April 6, 2007; revision received June 11, 2007; accepted June 11, 2007
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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), we showed that the inhibitory effect of exogenous estrogens on testosterone production is masked in the whole testis at later stages (20.5 dpc) due essentially to local production of estrogens. In both systems, additions of high concentrations (10-6 M) of 17ß-estradiol (E2) or diethylstilbestrol (DES) 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.
Key Words: testis development; fetus; neonate; gonocyte; Leydig; testosterone; estrogen.
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