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首页> 外文期刊>Brain research >Sex differences in the adult HPA axis and affective behaviors are altered by perinatal exposure to a low dose of bisphenol A
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Sex differences in the adult HPA axis and affective behaviors are altered by perinatal exposure to a low dose of bisphenol A

机译：围产期暴露于低剂量双酚A会改变成人HPA轴的性别差异和情感行为

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Bisphenol A (BPA), an estrogen-mimicking endocrine disrupter, when administered perinatally can affect affective behaviors in adult rodents, however the underlying mechanisms remain largely unclear. Postnatal day (PND) 80 vehicle-injected control female rats showed more obvious depression- and anxiety-like behaviors than males, indicative of sexually dimorphic affective behaviors. When female breeders were sub-cutaneously injected with BPA (2 ng/kg) from gestation day 10 to lactation day 7, sex difference of affective behaviors was impaired in their offspring (PND80 BPA-rats), as results that female BPA-rats showed a visible "antianxiety-like" behavior, and male BPA-rats increased depression-like behavior compared to vehicle-injected controls. Notably, basal levels of serum corticosterone and adrenocorticotropin (ACTH), and corticotropin-releasing hormone mRNA were increased in male BPA-rats, but not in female BPA-rats, in comparison with vehicle-injected controls. Following mild-stressor the elevation of corticosterone or ACTH levels was higher in male BPA-rats, whereas it was lower in female BPA-rats than vehicle-injected controls. In comparison with vehicle-injected controls, the level of glucocorticoid receptor (GR) mRNA in hippocampus or hypothalamic paraventricular nucleus was increased in female BPA-rats, while decreased in male BPA-rats. In addition, the levels of hippocampal mineralocorticoid receptor (MR) mRNA, neuronal nitric oxide synthase (nNOS) and phospho-cAMP response element binding protein (p-CREB) were increased in female BPA-rats, but were decreased in male BPA-rats. Furthermore, the testosterone level was reduced in male BPA-rats. The results indicate that the perinatal exposure to BPA through altering the GR and MR expression disrupts the GR-mediated feedback of hypothalamic-pituitary-adrenal (HPA) axis and MR-induced nNOS-CREB signaling, which alters sex difference in affective behaviors.
机译：双酚A（BPA）是一种模拟雌激素的内分泌干扰物，在围产期给药时可能会影响成年啮齿动物的情感行为，但是其潜在机制仍不清楚。出生后一天（PND）注射80支媒介物的雌性大鼠比雄性大鼠表现出更明显的抑郁和焦虑样行为，表明性二态性情感行为。从妊娠第10天到哺乳第7天，对雌性种鸽皮下注射BPA（2 ng / kg），其后代（PND80 BPA-rats）的情感行为性别差异被削弱，结果表明，雌性BPA-rats可见的“抗焦虑样”行为，并且与车辆注射的对照组相比，雄性BPA鼠增加了抑郁样行为。值得注意的是，与溶媒注射的对照组相比，雄性BPA大鼠的血清皮质激素和肾上腺皮质激素（ACTH）以及促肾上腺皮质激素释放激素的mRNA水平增加，但雌性BPA大鼠则没有。轻度应激后，雄性BPA大鼠的皮质酮或ACTH水平升高，而雌性BPA大鼠的皮质醇或促肾上腺皮质激素水平低于媒介物注射对照组。与溶媒注射的对照组相比，雌性BPA大鼠的海马或下丘脑室旁核中糖皮质激素受体（GR）mRNA的水平升高，而雄性BPA大鼠的糖皮质激素受体（GR）mRNA升高。此外，雌性BPA大鼠的海马盐皮质激素受体（MR）mRNA，神经元一氧化氮合酶（nNOS）和磷酸化cAMP反应元件结合蛋白（p-CREB）的水平升高，而雄性BPA大鼠则降低。此外，雄性双酚A大鼠的睾丸激素水平降低。结果表明，围产期通过改变GR和MR表达暴露于BPA会破坏GR介导的下丘脑-垂体-肾上腺（HPA）轴和MR诱导的nNOS-CREB信号传导，从而改变情感行为中的性别差异。

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