Low-dose in utero effects of xenoestrogens in mice and their relevance to humans: an analytical review of the literature

Several lines of evidence suggest that mouse embryos are sensitive to naturally-occurring and environmental estrogens. These include prostatic enlargement post-partum in male fetuses exposed in utero to low doses of estradiol, diethylstilbestrol (DES) or bisphenol A (BPA). The NIEHS/EPA Endocrine Disruptors Low Dose Peer Review Panel evaluated the relevant studies and concluded that while credible evidence exists for low dose effects of BPA, the effect had not been established as a “general and reproducible finding” based on the number and power of negative studies. The Panel suggested that the discrepancies in data were attributed to conditions, such as intrauterine position, environmental factors, and genetic factors. An issue that is potentially relevant to the health implications of low-dose xenoestrogen exposure in utero, and not previously addressed, is the comparative physiology of gestation in the mouse and human. These two species differ with regard to the extent of involvement and hormonal control of the corpus luteum, organs involved in progestin and estrogen secretion, the specific estrogens produced, and estrogen blood levels attained in the mother and embryo. On the basis of these species differences (particularly, the markedly higher estrogen levels attained in human pregnancy compared to the mouse), it would appear unlikely that low doses of BPA or other xenoestrogens produce adverse endocrine disruptive effects during human pregnancy.