Developmental exposure to bisphenol A: Interaction with endogenous estradiol during pregnancy in mice

Abstract

SYNOPSIS. Individual variability in endogenous hormones can confound the interpretation of effects of developmental exposure to endocrine disrupting chemicals. In single-birth species, such as humans, there are many sources of variability in fetal sex hormone levels, such as birth order or race. In litter-bearing species a source of fetal variability in serum levels of estradiol and testosterone is the sex of adjacent fetuses due to fetus-to-fetus steroid transport (called the intrauterine position phenomenon or IUP). Distinct phenotypes of reproductive physiology and behavior are due to IUP in house mice and other litter-bearing animals. We review here the effects of background levels of sex steroids in fetuses due to IUP in an experiment in which pregnant mice were exposed to an environmentally relevant low dose of the estrogen-mimicking chemical, bisphenol A. Bisphenol A is the monomer used to make polycarbonate plastic products (such as baby bottles), the resin lining of food and beverage cans, dental sealants, and a host of other products. Fetal exposure via the mother to bisphenol A increased the rate of postnatal growth in males and females and also advanced the timing of puberty in females. However, the greatest response to bisphenol A occurred in males and females with the highest background levels of endogenous estradiol during fetal life due to their IUP, while fetuses with the lowest endogenous levels of estradiol showed no response to maternal bisphenol A treatment. This finding suggests that estrogenmimicking chemicals interact with endogenous estrogen in altering the course of development.