Epidemiological investigations have found that maternal alcohol intake increases the risk of mental illness in offspring. Our study investigated changes of depression- and anxiety-like behaviors in adult offspring caused by prenatal ethanol exposure (PEE) and explored the potential mechanism. After Wistar rats were intragastrically administered ethanol at a dose of 4 g/kg·d on the 9–20 t h days of pregnancy, the offspring were given 21 days of chronic unpredictable mild stress (CUMS) starting from the 9th week after birth. Before CUMS, the behavioral results showed that the PEE offspring appeared excited and anxious. After CUMS, the PEE offspring rats were more sensitive to the same intensity of stimulation, and then the behavioral disorders aggravated. In adult offspring from the PEE group, the intercellular space was enlarged in the hippocampus, and there was a loss of pyramidal cells. The expression of brain-derived neurotrophic factor (BDNF) decreased; the mRNA expression of the glucocorticoid receptor and synaptic plasticity-related genes decreased; the apoptosis-related genes expressed disrupted. In order to determine whether hippocampal injury and dysfunction resulted from ethanol directly or indirectly, we performed in vitro study. The outcome was accompanied by disrupted gene expression related to neurogenesis and synaptic plasticity. PEE increases the susceptibility of adult female offspring to depression- and anxiety-like behaviors, and its mechanism may be related to the toxic effects of ethanol, both directly and indirectly. The latter inhibits the hippocampal BDNF pathway, leading to the disruption of hippocampal neurogenesis, apoptosis and decreased synaptic plasticity.

流行病学调查发现，母亲饮酒会增加后代患精神疾病的风险。我们的研究调查了产前乙醇暴露（PEE）引起的成年后代抑郁和焦虑样行为的变化，并探讨了潜在的机制。 Wistar大鼠在妊娠第9~20天按4 g/kg·d剂量灌胃乙醇后，子代从出生第9周开始接受21天的慢性不可预测温和应激（CUMS）。在 CUMS 之前，行为结果显示 PEE 后代表现出兴奋和焦虑。 CUMS后，PEE子代大鼠对相同强度的刺激更加敏感，行为障碍加重。在PEE组的成年后代中，海马体的细胞间隙扩大，锥体细胞减少。脑源性神经营养因子（BDNF）表达减少；糖皮质激素受体和突触可塑性相关基因的mRNA表达降低；凋亡相关基因的表达受到干扰。为了确定乙醇是否直接或间接导致海马损伤和功能障碍，我们进行了体外研究。结果伴随着与神经发生和突触可塑性相关的基因表达的破坏。 PEE增加成年女性后代对抑郁和焦虑样行为的易感性，其机制可能与乙醇的毒性作用直接或间接有关。后者抑制海马 BDNF 通路，导致海马神经发生破坏、细胞凋亡和突触可塑性下降。