Maternal exposure to bisphenol A and genistein has minimal effect on A(vy)/a offspring coat color but favors birth of agouti over nonagouti mice

Reports that maternal diet influences coat color in mouse offspring carrying the agouti A(vy) allele have received considerable attention because the range, from pseudoagouti (brown) to yellow, predicts adult health outcomes, especially disposition toward obesity and diabetes, in yellower mice. Bisphenol A (BPA), an endocrine-disrupting compound with estrogenic properties, fed to a/a dams harboring A(vy)/a conceptuses has been reported to induce a significant shift toward yellower mice, whereas consumption of either genistein (G) alone or in combination with BPA led to greater numbers of healthy, brown offspring. Groups of C57/B6 a/a females, which are nonagouti, were fed either a phytoestrogen-free control diet or one of six experimental diets: diets 1-3 contained BPA (50 mg, 5 mg, and 50 μg BPA/kg food, respectively); diet 4 contained G (250 mg/kg food); diet 5 contained G plus BPA (250 and 50 mg/kg food, respectively); and diet 6 contained 0.1 μg of ethinyl estradiol (EE)/kg food. Mice were bred to A(vy)/a males over multiple parities. In all, 2,824 pups from 426 litters were born. None of the diets provided any significant differences in relative numbers of brown, yellow, or intermediate coat color A(vy)/a offspring. However, BPA plus G (P < 0.0001) and EE diets (P = 0.005), but not the four others, decreased the percentage of black (a/a) to A(vy)/a offspring from the expected Mendelian ratio of 1:1. Data suggest that A(vy)/a conceptuses, which may possess a so-called "thrifty genotype," are at a competitive advantage over a/a conceptuses in certain uterine environments.