This study was designed to demonstrate disorder of hypothalamic-pituitary-adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration and dysfunction of glucose and lipid metabolism induced by prenatal ethanol exposure (PEE) in postnatal week 40 (PW40) female offspring rats. Pregnant Wistar rats were administrated 4  g/kg·d ethanol intragastrically from gestational day 11 until term delivery. After weaning, the female offspring were fed with high-fat diet until PW24, and suffered to unpredictable chronic stress (UCS) during PW38-40. Animal serum was collected to examine the changes in hypothalamic-pituitary-adrenal (HPA) axis activity, glucose and lipid metabolic phenotypes before and after UCS. We found that pups in the PEE group manifested a low birthweight at PW1 and an early catch-up growth pattern. Furthermore, a low basal activity of HPA axis continued to PW38 in the PEE group. On the basal condition, serum low-density lipoprotein-cholesterol (LDL-C) level was significantly increased and high-density lipoprotein-cholesterol (HDL-C) level was significantly decreased in the PEE group, while serum triglyceride, total cholesterol (TCH), glucose and insulin levels were not significantly changed. Under unpredictable chronic stress, serum insulin in the PEE group was significantly decreased, while the levels of serum triglyceride, TCH, LDL-C, and the ratio of LDL-C/HDL-C were significantly higher than those in the control. These results suggest that PEE increases the dysfunction of glucose and lipid metabolism in PW40 female offspring, which is related to the disorder of HPA axis-associated neuroendocrine metabolic programming alteration.

中文翻译：

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产前乙醇暴露引起40周龄雌性后代大鼠下丘脑-垂体-肾上腺轴相关的神经内分泌代谢程序改变和糖脂代谢功能异常。

这项研究旨在证明在产后40周（PW40）的雌性后代大鼠中，下丘脑-垂体-肾上腺（HPA）轴相关的神经内分泌代谢程序改变以及产前乙醇暴露（PEE）引起的葡萄糖和脂质代谢功能异常。从妊娠第11天到足月分娩，对怀孕的Wistar大鼠胃内给予4 g / kg·d乙醇。断奶后，对雌性后代进行高脂饮食直至PW24，并在PW38-40期间遭受不可预测的慢性应激（UCS）。收集动物血清以检查UCS之前和之后下丘脑-垂体-肾上腺（HPA）轴活性，葡萄糖和脂质代谢表型的变化。我们发现，PEE组的幼崽在PW1时出生体重低，并且追赶生长方式早。此外，PEE组中，HPA轴的低基础活性持续至PW38。在基础条件下，PEE组血清低密度脂蛋白胆固醇（LDL-C）水平显着升高，高密度脂蛋白胆固醇（HDL-C）水平显着下降，而血清甘油三酯，总胆固醇（TCH） ），葡萄糖和胰岛素水平没有明显改变。在无法预测的慢性应激下，PEE组的血清胰岛素显着降低，而血清甘油三酯，TCH，LDL-C和LDL-C / HDL-C的比例则明显高于对照组。这些结果表明，PEE增加了PW40雌性后代中葡萄糖和脂质代谢的功能障碍，这与HPA轴相关的神经内分泌代谢编程改变的疾病有关。