McGivern R F, Sokol R Z, Berman N G
Department of Medicine, UCLA School of Medicine, Torrance 90509.
Toxicol Appl Pharmacol. 1991 Sep 1;110(2):206-15. doi: 10.1016/s0041-008x(05)80003-1.
Sprague-Dawley dams were administered lead acetate (0.1%) in their drinking water from Day 14 of gestation to parturition to determine whether exposure of the fetus to elevated lead (Pb) levels during a period of rapid differentiation of the hypothalamic-pituitary-gonadal (HPG) axis would disrupt HPG function in adulthood. At birth, offspring from 20 Pb-treated and 10 control dams were weighed and 2 litter representatives from each sex were fostered to untreated dams. Animals were weaned at 26 days of age and subsequently group housed by sex and treatment. Blood Pb levels in prenatally exposed pups were below the limits of detectability at weaning. Female offspring from Pb-treated dams were found to have a significant delay in the day of vaginal opening. In a sample of lead exposed females, 50% were found to exhibit prolonged and irregular periods of diestrous which was accompanied by an absence of observable corpora lutea when they were euthanized at 83 days of age. Male offspring from these dams were found to have decreased sperm counts at 70 and 160 days of age and to exhibit significantly less territorial scent marking and masculine sex behavior in adulthood compared to controls. Azoospermia was observed in 1 lead exposed animal at 70 days of age and 2 animals at 160 days. Enlarged prostates were observed in Pb-exposed males measured at 160 days, but other sex organ weights were normal. Volume of the sexually dimorphic nucleus of the preoptic area of the hypothalamus in adulthood was significantly reduced by approximately 35% in Pb-exposed males. Pulsatile release of gonadotropins, measured in castrated adult animals of both sexes, revealed irregular release patterns of both FSH and LH in some Pb animals which were not observed in controls. The overall pattern of results suggests that multiple levels of the HPG axis can be affected by exposure to Pb during a period of gestation when structures related to the HPG axis are undergoing rapid proliferation. These data indicate that lead exposure during this period places the exposed animal at significant risk for reduced reproductive capacity in adulthood.
从妊娠第14天到分娩，给斯普拉格-道利母鼠饮用含0.1%醋酸铅的水，以确定在丘脑下部-垂体-性腺（HPG）轴快速分化期间，胎儿暴露于升高的铅（Pb）水平是否会破坏成年期的HPG功能。出生时，对20只经铅处理母鼠和10只对照母鼠的后代进行称重，并将每种性别的2只窝代表寄养给未经处理的母鼠。动物在26日龄时断奶，随后按性别和处理方式分组饲养。产前暴露幼崽的血铅水平在断奶时低于可检测限度。发现经铅处理母鼠的雌性后代阴道开口日明显延迟。在一组铅暴露雌性动物中，发现50%表现出延长且不规律的间情期，在83日龄安乐死时未观察到黄体。与对照组相比，这些母鼠的雄性后代在70日龄和160日龄时精子数量减少，成年期表现出明显较少的领地气味标记和雄性性行为。在1只70日龄的铅暴露动物和2只160日龄的动物中观察到无精子症。在160日龄时测量，铅暴露雄性动物的前列腺增大，但其他性器官重量正常。成年期，铅暴露雄性动物下丘脑视前区性二态核的体积显著减少约35%。在两性去势成年动物中测量促性腺激素的脉冲释放，发现一些铅处理动物中促卵泡激素（FSH）和促黄体生成素（LH）的释放模式不规则，而对照组未观察到这种情况。总体结果模式表明，在与HPG轴相关的结构正在快速增殖的妊娠期，暴露于铅会影响HPG轴的多个水平。这些数据表明，在此期间铅暴露使暴露动物在成年期生殖能力降低方面面临重大风险。
