Bisphenol A (BPA) is a ubiquitous industrial chemical used in the production of a wide variety of items. Previous studies suggest BPA exposure may result in neuro-disruptive effects; however, data are inconsistent across animal and human studies. As part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA), we sought to determine whether female and male rats developmentally exposed to BPA demonstrated later spatial navigational learning and memory deficits. Pregnant NCTR Sprague-Dawley rats were orally dosed from gestational day 6 to parturition, and offspring were directly orally dosed until weaning (postnatal Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ) and a 0.5 μg/kg/day ethinyl estradiol (EE)-reference estrogen dose. At adulthood, 1/sex/litter was tested for seven days in the Barnes maze. The 2500 BPA group sniffed more incorrect holes on day 7 than those in the control, 2.5 BPA, and EE groups. The 2500 BPA females were less likely than control females to locate the escape box in the allotted time (P value= 0.04). Although 2.5 BPA females exhibited a prolonged latency, the effect did not reach significance (P value = 0.06), whereas 2.5 BPA males showed improved latency compared to control males (P value = 0.04), although the significance of this result is uncertain. No differences in serum testosterone concentration were detected in any male or female treatment groups. Current findings suggest developmental exposure of rats to BPA may disrupt aspects of spatial navigational learning and memory. HHS Public Access

The nature and extent of care received by an infant can affect social, emotional and cognitive development, features that endure into adulthood. Here we employed the monogamous, California mouse (Peromyscus californicus), a species, like the human, where both parents invest in offspring care, to determine whether early exposure to endocrine disrupting chemicals (EDC: bisphenol A, BPA; ethinyl estradiol, EE) of one or both parents altered their behaviors towards their pups. Females exposed to either compound spent less time nursing, grooming and being associated with their pups than controls, although there was little consequence on their weight gain. Care of pups by males was less affected by exposure to BPA and EE, but control, non-exposed females appeared able to “sense” a male partner previously exposed to either compound and, as a consequence, reduced their own parental investment in offspring from such pairings. The data emphasize the potential vulnerability of pups born to parents that had been exposed during their own early development to EDC, and that effects on the male, although subtle, also have consequences on overall parental care due to lack of full acceptance of the male by the female partner.

Endocrine disrupting chemicals (EDC) have received considerable attention as potential obesogens. Past studies examining obesogenic potential of one widespread EDC, bisphenol A (BPA), have generally focused on metabolic and adipose tissue effects. However, physical inactivity has been proposed to be a leading cause of obesity. A paucity of studies has considered whether EDC, including BPA, affects this behavior. To test whether early exposure to BPA and ethinyl estradiol (EE, estrogen present in birth control pills) results in metabolic and such behavioral disruptions, California mice developmentally exposed to BPA and EE were tested as adults for energy expenditure (indirect calorimetry), body composition (echoMRI) and physical activity (measured by beam breaks and voluntary wheel running). Serum glucose and metabolic hormones were measured. No differences in body weight or food consumption were detected. BPA-exposed females exhibited greater variation in weight than females in control and EE groups. During the dark and light cycles, BPA females exhibited a higher average respiratory quotient than control females, indicative of metabolizing carbohydrates rather than fats. Various assessments of voluntary physical activity in the home cage confirmed that during the dark cycle, BPA and EE-exposed females were significantly less active in this setting than control females. Similar effects were not observed in BPA or EE-exposed males. No significant differences were detected in serum glucose, insulin, adiponectin and leptin concentrations. Results suggest that females developmentally exposed to BPA exhibit decreased motivation to engage in voluntary physical activity and altered metabolism of carbohydrates v. fats, which could have important health implications.

Maternal diet-induced obesity can cause detrimental developmental origins of health and disease in offspring. Perinatal exposure to a high-fat diet (HFD) can lead to later behavioral and metabolic disturbances, but it is not clear which behaviors and metabolic parameters are most vulnerable. To address this critical gap, biparental and monogamous oldfield mice (Peromyscus polionotus), which may better replicate most human societies, were used in the current study. About 2 weeks before breeding, adult females were placed on a control or HFD and maintained on the diets throughout gestation and lactation. F 1 offspring were placed at weaning (30 days of age) on the control diet and spatial learning and memory, anxiety, exploratory, voluntary physical activity, and metabolic parameters were tested when they reached adulthood (90 days of age). Surprisingly, maternal HFD caused decreased latency in initial and reverse Barnes maze trials in male, but not female, offspring. Both male and female HFD-fed offspring showed increased anxiogenic behaviors, but decreased exploratory and voluntary physical activity. Moreover, HFD offspring demonstrated lower resting energy expenditure (EE) compared with controls. Accordingly, HFD offspring weighed more at adulthood than those from control fed dams, likely the result of reduced physical activity and EE. Current findings indicate a maternal HFD may increase obesity susceptibility in offspring due to prenatal programming resulting in reduced physical activity and EE later in life. Further work is needed to determine the underpinning neural and metabolic mechanisms by which a maternal HFD adversely affects neurobehavioral and metabolic pathways in offspring.

Rodent species, such as monogamous and biparental California mice, produce vocalizations as a means of communication. A temporal examination of vocalizations produced by California mice pups in isolation was performed. Pup recordings were performed for 3 minutes at ~10.00 and 14.00 hrs on early postnatal days (PND) 2-4, 7, 21, and 28. Once initial recordings were finished, pups were returned to the home cage with parents and any siblings for five minutes to determine if active biparental responses resulted in an enhanced vocalization response when pups were isolated and retested. We also sought to determine whether potential reduction in vocalizations by older pups might be due to procedure-habituation procedure associated with less anxiety and/or possibly decreased need for parental care. Vocalizations were measured in weanling (30 days of age) "naïve" pups not previously isolated. Results show older pups took significantly longer to vocalize, indicated by increased latency before producing their initial syllable compared to earlier ages. With increasing age, pups demonstrated decreased syllable duration, reduced number and duration of phrases, and decreased number of syllables per phrase. No differences in pup vocalizations were observed before and after being placed back with parents, suggestive biparernal potentiation may not exist in California mice pups. Comparison of the naïve to habituated