Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production

This study assessed whether exposure of male rats to two estrogenic, environmental chemicals, 4-octylphenol (OF) and butyl benzyl phthalate (BBP) during gestation or during the first 21 days of postnatal life, affected testicular size or spermatogenesis in adulthood (90-95 days of age). Chemicals were administered via the drinking water at concentrations of 10-1000 mu g/l (OF) or 1000 mu g/l (BBP); diethylstilbestrol (DES; 100 mu g/l) and an octylphenol polyethoxylate (OPP; 1000 mu g/l), which is a weak estrogen or nonestrogenic in vitro, were administered as presumptive positive and negative controls, respectively. Controls received the vehicle (ethanol) in tapwater. In study 1, rats were treated from days 1-22 after birth; in studies 2 and 3, the mothers were treated for approximately 8-9 weeks, spanning a 2-week period before mating, throughout gestation and up until 22 days after giving birth. With the exception of DES, treatment generally had no major adverse effect on body weight: in most instances, treated animals were heavier than controls at day 22 and at days 90-95. Exposure to OF, OPP, or BBP at a concentration of 1000 mu g/l resulted in a small (5-13%) but significant (p<0.01 or p<0.001) reduction in mean testicular size in studies 2 and 3, an effect that was still evident when testicular weight was expressed relative to body weight or kidney weight. The effect of OPP is attributed to its metabolism in vivo to OF. DES exposure caused similar reductions in testicular size but also caused reductions in body weight, kidney weight, and litter size. Ventral prostate weight was reduced significantly in DES-treated rats and to a minor extent in OP-treated rats. Comparable but more minor effects of treatment with DES or OP on testicular size were observed in study 1. None of the treatments had any adverse effect on testicular morphology or on the cross-sectional area of the lumen or seminiferous epithelium at stages VII-VIII of the spermatogenic cycle, but DES, OF, and BBP caused reductions of 10-21% (p<0.05 to p<0.001) in daily sperm production. Humans are exposed to phthalates, such as BBP, and to alkylphenol polyethoxylates, such as OF, but to what extent is unknown. More detailed studies are warranted to assess the possible risk to the development of the human testis from exposure to these and other environmental estrogens.