Salian Smita, Doshi Tanvi, Vanage Geeta
National Center for Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health (ICMR), J M Street, Parel, Mumbai, Maharashtra, 400 012, India.
Life Sci. 2009 Nov 18;85(21-22):742-52. doi: 10.1016/j.lfs.2009.10.004. Epub 2009 Oct 21.
The exposure to endocrine disruptor (ED) induces functional and behavioral abnormalities associated with reproduction. Humans are ubiquitously exposed to Bisphenol A (BPA), an ED, as it leaches from polycarbonate plastics into their contents. The aim of the present study was to determine the effect of perinatal exposure of male rats to BPA on fertility parameters and perturbations in the expression of testicular steroid receptors (SRs) in adult F(1) offspring. These effects were studied in adult males of the F(2) and F(3) generations to determine the vertical transmission of BPA exposure.
Pregnant female rats (F(0)) were gavaged with either BPA (1.2 and 2.4 microg/kg bw), a vehicle control or positive control with Diethylstilbestrol (10 microg/kg bw) during the perinatal period. Adult F(1) males were subjected to fertility assessment by mating with unexposed females. The reproductive functions of the subsequent F(2) and F(3) litters were investigated in a similar manner. Immunohistochemical localization of SRs was carried out in the testes of F(1), F(2) and F(3) generation adult rats.
A significant increase in post implantation loss and a decrease in litter size and sperm count and motility were observed in the F(1) male offspring. A reduction in the testicular expression profile of SRs was observed. These effects were very prominent in the subsequent F(2) and F(3) generations.
Perinatal exposure to environmentally relevant doses of BPA affects the male germ line, leading to impairments in the fertility of F(1) male offspring and their subsequent F(2) and F(3) generations.
接触内分泌干扰物（ED）会引发与生殖相关的功能和行为异常。人类普遍接触双酚A（BPA）这种内分泌干扰物，因为它会从聚碳酸酯塑料中渗出到其所含物质中。本研究的目的是确定雄性大鼠围产期接触双酚A对成年F1代后代生育参数以及睾丸类固醇受体（SRs）表达紊乱的影响。在F2和F3代成年雄性大鼠中研究这些影响，以确定双酚A暴露的垂直传播情况。
在围产期，给怀孕的雌性大鼠（F0）灌胃双酚A（1.2和2.4微克/千克体重）、溶剂对照或己烯雌酚阳性对照（10微克/千克体重）。成年F1代雄性大鼠与未接触的雌性大鼠交配以进行生育力评估。以类似方式研究后续F2和F3代幼崽的生殖功能。在F1、F2和F3代成年大鼠的睾丸中进行类固醇受体的免疫组织化学定位。
在F1代雄性后代中观察到着床后损失显著增加、窝仔数、精子数量和活力减少。观察到睾丸中类固醇受体的表达谱降低。这些影响在后续F2和F3代中非常显著。
围产期接触环境相关剂量的双酚A会影响雄性生殖系，导致F1代雄性后代及其后续F2和F3代的生育力受损。
