Effects of fetal and neonatal exposure of male mice to diethylstilbestrol as endocrine disrupter on the reproductive and neuroendocrine system

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The purpose of this study is to determine the effect of fetal and neonatal exposure to diethylstilbestrol (DBS), as a representative endocrine disrupter, on the reproductive function of male mice. Various doses (0.001-100 μg) of DES or a vehicle (control) were administered to the neonatal group on day 3 (single) and on every 2 days from day 3 (N-long-term), and to the fetal group every 2 days from 7 dpc (F-long-term). Endocrinological and morphological changes were evaluated at 25 days of age (immediately before the onset of puberty), 4, 6, 8, and 12 weeks of age. We established a non-RI solid phase immunoassay method, which enables multiple microassay (LH, FSH, PRL, testosterone, inhibin) of the same sample with high sensitivity and specificity. In single administration of 10 and 100 μg of DES at 4 weeks, N-long-term administration at 1.0 μg for 25 days and 10 μg for 6 weeks, aid F-long-term administration at 10 μg for 6 weeks, testis weights were significantly reduced, and no spermat … More ogenesis and immature seminiferous tubules were observed. DES injections caused dose-dependent retardation of pituitary LH, FSH. Using the morphometric immunodetection method for incorporated thymidine analog BrdU, the high-dose groups (10 ＆ 100 μg) showed a marked disruption of sperm production and significant suppression of cellular proliferation in testes. Immunohistochemical analysis in each group showed that immunoreactive neurons for GnRH were generally fewer in number and had thinner neurites in the high-dose groups Immunoreactivity of Era and StAR (steroidogenic acute regulatory protein) in testes was decreased. Thus our findings indicate that 1) single neonatal exposure of male mice to 10 μg of DES can advance the spermatogenesis at 6 weeks of age; 2) long-term exposure of these mice, particularly from fetus, could not recover the spermatogenesis even under 1.0 μg of DES; and 3) there is threshold dose of DES, and these delay and damage in the reproduction system due to reduction of pituitary gonadotropin production. Less