Hypothalamic gene expression changes in F1 California mice (Peromyscus californicus) parents developmentally exposed to bisphenol A or ethinyl estradiol

Abstract

Bisphenol A (BPA) is a pervasive industrial chemical used in many common household items. To examine how early exposure to BPA and ethinyl estradiol (EE, estrogen in birth control pill) might affect biparental care, effects of these chemicals in male and female California mice (Peromyscus californicus), who are monogamous and biparental, were examined. California mice exposed during pre- and peri-natal life to BPA at an environmentally relevant concentration or EE show later disrupted biparental behaviors. The hypothalamus is an important brain region for regulating parental behaviors. Thus, it was hypothesized compromised biparental care might be partially due to hypothalamic gene alterations. To address this question, brains from F1 parenting female and male California mice from controls, BPA- and EE-exposed groups were collected at postnatal day (PND) 2, and RNA was isolated from hypothalamic micropunches. Gene expression was examined in this brain region for genes affected by BPA exposure and attributed to governing parental care in rodents and humans. BPA-exposed California mice showed increased hypothalamic expression of Kiss1, Esr1 and Esr2 relative to AIN control and EE-exposed parents in the case of Esr2. Notably, current studies represent the first report to show that early exposure to BPA can induce longstanding effects on hypothalamic gene expression in parenting male and female rodents. Absence of such hypothalamic gene expression changes in EE-exposed parents indicates early BPA exposure may induce later transcriptomic effects through estrogen receptor-independent pathways. BPA-driven changes in hypothalamic function of California mice might contribute to decreased biparental investment, which could result in F2 multigenerational effects.