Aggressive behavior and serum testosterone concentration during the maturation process of male mice: the effects of fetal exposure to bisphenol A.

Abstract

The relationship between exposure to endocrine-disrupting chemicals (EDs) and risk to reproductive organs is well documented, but the influence of EDs on behavioral development has not been studied. In this study we evaluated the effect of fetal exposure to bisphenol A, which mimics estrogenic activity, on aggressive behavior and hormonal change in male mice. On gestation days 11-17, female mice were fed bisphenol A at 2 ng/g or 20 ng/g of body weight (environmentally relevant concentration). Aggression rating and blood sampling of the offspring were done at 8, 12, and 16 weeks of age. Aggression scores increased significantly (p < 0.01) at 8 weeks of age in male mice exposed to bisphenol A at both the 2 ng/g and 20 ng/g concentrations compared with a control group, but no difference was found after 12 weeks. Relative testis weight (per gram of body weight) was significantly lower at 8 and 12 weeks in mice treated with 2 ng/g than in controls (p < 0.05) and was significantly lower at 12 weeks in mice treated with 20 ng/g than in controls (p < 0.01). The serum testosterone concentration in treated mice was not significantly different from that in controls. These results demonstrate that bisphenol A temporarily activated aggressive behavior in mice at 8 weeks of age and that low doses of bisphenol A interfered with the normal development of reproductive organs. The mechanism activating this aggressive behavior was not elevated testosterone concentration.

Perinatal and Postnatal Exposure to Bisphenol A Increases Adipose Tissue Mass and Serum Cholesterol Level in Mice

“…This is consistent with the finding of Rubin et al 9) that, in female rats exposed perinatally to BPA, the lower of the two BPA doses (0.1 and 1.2 mg/kg body weight/day) produced a larger effect on body weight relative to the higher dose. Similar nonmonotonic and inverted-Ushaped dose-response curves of BPA were observed in measurements of preputial gland weight 31) and testis weight 32) in rodents. vom Saal et al 31) described that responses to weak environmental estrogens, including BPA, cannot be assumed to be monotonic across a wide dose range.…”

Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis

“…Before this study, the anti-androgenic properties of BPA had been described in various animal experiments (Kawai et al, 2003;Kabuto et al, 2004;Tanaka et al, 2006), in the human adrenocortical NCI-H295R cell line (Zhang et al, 2011), and in human and rat microsomes (Ye A c c e p t e d m a n u s c r i p t et al, 2011). Like BPA, some BPA-A were also shown to display anti-androgenicity in the steroidogenic NCI-H295R cell line (Rosenmai et al, 2014;Goldinger et al, 2015).…”

NTP‐CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A

“…Kawai et al (2003), supported by Core Research for Evolutional Science and Technology and Japan Science and Technology, examined the effects of prenatal bisphenol A exposure on aggressive behavior in male mice.…”