Prenatal lead exposure in the rat during the third week of gestation: long-term behavioral, physiological, and anatomical effects associated with reproduction.

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.