Exposure to a Low Dose of Bisphenol A during Fetal Life or in Adulthood Alters Maternal Behavior in Mice

Reproduced with permission from Environmental Health Perspectives.Maternal behavior in mammals is the result of a complex interaction between the lactating dam and her developing offspring. Slight perturbations of any of the components of the mother-infant interaction may result in alterations of the behavior of the mother and/or of the offspring. We studied the effects of exposure of female CD-1 mice to the estrogenic chemical bisphenol A (BPA) during fetal life and/or in adulthood during the last part of pregnancy on subsequent maternal behavior. Pregnant females were fed daily doses of corn oil (controls) or 10 μg/kg body weight BPA during gestation days 14-18. As adults, the prenatally treated female offspring were timemated and again fed either corn oil (controls) or the same doses of BPA on gestation days 14-18, resulting in four treatment groups: controls, prenatal BPA exposure, adult BPA exposure, and both prenatal and adult BPA exposure. Maternal behavior was then observed on postnatal days 2-15 and reflex responses were examined in the offspring. Dams exposed to BPA either as fetuses or in adulthood spent less time nursing their pups and more time out of the nest compared with the control group. Females exposed to BPA both as fetuses and in adulthood did not significantly differ from controls. No alterations in postnatal reflex development were observed in the offspring of the females exposed to BPA. The changes seen in maternal behavior may be the result of a direct effect of BPA on the neuroendocrine substrates underlying the initiation of maternal behavior.This research was supported by grants from NIEHS, NIH (ES08293), to F.V.S. and from the Italian Ministry of University and Scientific Research (MURST-COFIN2000), the University of Parma, and CNR (National Council for Research) to P.P

Exposure to a low dose of bisphenol A during fetal life or in adulthood alters maternal behavior in mice.

Maternal behavior in mammals is the result of a complex interaction between the lactating dam and her developing offspring. Slight perturbations of any of the components of the mother-infant interaction may result in alterations of the behavior of the mother and/or of the offspring. We studied the effects of exposure of female CD-1 mice to the estrogenic chemical bisphenol A (BPA) during fetal life and/or in adulthood during the last part of pregnancy on subsequent maternal behavior. Pregnant females were fed daily doses of corn oil (controls) or 10 microg/kg body weight BPA during gestation days 14-18. As adults, the prenatally treated female offspring were time-mated and again fed either corn oil (controls) or the same doses of BPA on gestation days 14-18, resulting in four treatment groups: controls, prenatal BPA exposure, adult BPA exposure, and both prenatal and adult BPA exposure. Maternal behavior was then observed on postnatal days 2-15 and reflex responses were examined in the offspring. Dams exposed to BPA either as fetuses or in adulthood spent less time nursing their pups and more time out of the nest compared with the control group. Females exposed to BPA both as fetuses and in adulthood did not significantly differ from controls. No alterations in postnatal reflex development were observed in the offspring of the females exposed to BPA. The changes seen in maternal behavior may be the result of a direct effect of BPA on the neuroendocrine substrates underlying the initiation of maternal behavior

Bisphenol A Is Released from Used Polycarbonate Animal Cages into Water at Room Temperature

doi:10.1289/ehp.5993Bisphenol A (BPA) is a monomer with estrogenic activity that is used in the production of food packaging, dental sealants, polycarbonate plastic, and many other products. The monomer has previously been reported to hydrolyze and leach from these products under high heat and alkaline conditions, and the amount of leaching increases as a function of use. We examined whether new and used polycarbonate animal cages passively release bioactive levels of BPA into water at room temperature and neutral pH. Purified water was incubated at room temperature in new polycarbonate and polysulfone cages and used (discolored) polycarbonate cages, as well as control (glass and used polypropylene) containers. The resulting water samples were characterized with gas chromatography/mass spectrometry (GC/MS) and tested for estrogenic activity using an MCF-7 human breast cancer cell proliferation assay. Significant estrogenic activity, identifiable as BPA by GC/MS (up to 310 µg/L), was released from used polycarbonate animal cages. Detectable levels of BPA were released from new polycarbonate cages (up to 0.3 µg/L) as well as new polysulfone cages (1.5 µg/L), whereas no BPA was detected in water incubated in glass and used polypropylene cages. Finally, BPA exposure as a result of being housed in used polycarbonate cages produced a 16% increase in uterine weight in prepubertal female mice relative to females housed in used polypropylene cages, although the difference was not statistically significant. Our findings suggest that laboratory animals maintained in polycarbonate and polysulfone cages are exposed to BPA via leaching, with exposure reaching the highest levels in old cages.Support during the preparation of this manuscript was provided by grants from the National Institutes of Health (CA50354) and the University of Missouri (VMFC0018) to W.V.W., NIH (ES08293 and ES11283) to F.v.S., and the U.S.G.S

Low Phytoestrogen Levels in Feed Increase Fetal Serum Estradiol Resulting in the “Fetal Estrogenization Syndrome” and Obesity in CD-1 Mice

doi:10.1289/ehp.10448Although estrogenic chemicals can disrupt development of the reproductive system, there is debate about whether phytoestrogens in soy are beneficial, benign, or harmful. We compared reproductive and metabolic characteristics in male and female mice reared and maintained on non-soy low-phytoestrogen feed or soy-based high-phytoestrogen feed. Removing phytoestrogens from mouse feed produces an obese phenotype consistent with metabolic syndrome, and the associated reproductive system abnormalities are consistent with FES due to elevated endogenous fetal estradiol. Laboratory rodents may have become adapted to high-phytoestrogen intake over many generations of being fed soy-based commercial feed; removing all phytoestrogens from feed leads to alterations that could disrupt many types of biomedical research

Low Phytoestrogen Levels in Feed Increase Fetal Serum Estradiol Resulting in the “Fetal Estrogenization Syndrome” and Obesity in CD-1 Mice

doi:10.1289/ehp.10448Although estrogenic chemicals can disrupt development of the reproductive system, there is debate about whether phytoestrogens in soy are beneficial, benign, or harmful. We compared reproductive and metabolic characteristics in male and female mice reared and maintained on non-soy low-phytoestrogen feed or soy-based high-phytoestrogen feed. Removing phytoestrogens from mouse feed produces an obese phenotype consistent with metabolic syndrome, and the associated reproductive system abnormalities are consistent with FES due to elevated endogenous fetal estradiol. Laboratory rodents may have become adapted to high-phytoestrogen intake over many generations of being fed soy-based commercial feed; removing all phytoestrogens from feed leads to alterations that could disrupt many types of biomedical research