RESUMO
Adverse experiences during pregnancy induce placental programming, affecting the fetus and its developmental trajectory. However, the influence of 'positive' maternal experiences on the placenta and fetus remain unclear. In animal models of early life stress, environmental enrichment (EE) has ameliorated and even prevented associated impairments in brain and behavior. Here, using a maternal immune activation (MIA) model in rats, we test whether EE attenuates maternal, placental and/or fetal responses to an inflammatory challenge, thereby offering a mechanism by which fetal programming may be prevented. Moreover, we evaluate life-long EE exposure on offspring development and examine a constellation of genes and epigenetic writers that may protect against MIA challenges. In our model, maternal plasma corticosterone and interleukin-1ß were elevated 3â¯h after MIA, validating the maternal inflammatory response. Evidence for developmental programming was demonstrated by a simultaneous decrease in the placental enzymes Hsd11b2 and Hsd11b2/Hsd11b1, suggesting disturbances in glucocorticoid metabolism. Reductions of Hsd11b2 in response to challenge is thought to result in excess glucocorticoid exposure to the fetus and altered glucocorticoid receptor expression, increasing susceptibility to behavioral impairments later in life. The placental, but not maternal, glucocorticoid implications of MIA were attenuated by EE. There were also sustained changes in epigenetic writers in both placenta and fetal brain as a consequence of environmental experience and sex. Following MIA, both male and female juvenile animals were impaired in social discrimination ability. Life-long EE mitigated these impairments, in addition to the sex specific MIA associated disruptions in central Fkbp5 and Oprm1. These data provide the first evidence that EE protects placental functioning during stressor exposure, underscoring the importance of addressing maternal health and well-being throughout pregnancy. Future work must evaluate critical periods of EE use to determine if postnatal EE experience is necessary, or if prenatal exposure alone is sufficient to confer protection.
Assuntos
Desenvolvimento Fetal/imunologia , Placenta/imunologia , Efeitos Tardios da Exposição Pré-Natal/imunologia , 11-beta-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Feminino , Feto/imunologia , Glucocorticoides/metabolismo , Masculino , Placenta/enzimologia , Placenta/metabolismo , Gravidez , RatosRESUMO
Bisphenol A (BPA) is widely used in the polycarbonate plastics and epoxy resins that are found in laboratory animal husbandry materials including cages and water bottles. Concerns about BPA exposure in humans has led to investigations that suggest physiologic health risks including disruptions to the endocrine system and CNS. However, the extent of exposure of laboratory animals to BPA in drinking water is unclear. In the first study, we compared the amount of BPA contamination in water stored in plastic bottles used in research settings with that in glass bottles. The amount of BPA that leached into water was measured across several time points ranging from 24 to 96 h by using a BPA ELISA assay. The results showed that considerable amounts of BPA (approximately 0.15 µg/L) leached from polycarbonate bottles within the first 24 h of storage. In the second study, BPA levels were measured directly from water taken from filtered compared with unfiltered taps. We observed significantly higher BPA levels in water from unfiltered taps (approximately 0.40 µg/L) compared with taps with filtration systems (approximately 0.04 µg/L). Taken together, our findings indicate that the use of different types of water bottles and water sources, combined with the use of different laboratory products (food, caging systems) between laboratories, likely contribute to decreased rigor and reproducibility in research. We suggest that researchers consider reporting the types of water bottles used and that animal care facilities educate staff regarding the importance of flushing nonfiltered water taps when filling animal water bottles.