Department of Molecular Biology, Ariel University, Ariel, 4070000, Israel.
Sci Rep. 2018 Jun 25;8(1):9595. doi: 10.1038/s41598-018-27988-9.
The developing fetus is highly sensitive to prenatal stress, which may alter Hypothalamic-Pituitary-Adrenal (HPA) axis programming and increase the risk of behavioral disorders. There is high variability among the human population, wherein many offspring of stressed pregnancies display resilience to adversity, while the remainder displays vulnerability. In order to identify biological substrates mediating between resilience or vulnerability to prenatal adversity, we exposed stress-resistant Dominant (Dom) and stress-sensitive Submissive (Sub) mice to mild prenatal restraint stress (PRS, 45 min on gestational days (GD) 15, 16 and 17). We hypothesized that PRS would differentially alter prenatal programming of limbic regions regulating the HPA axis and affect among Dom and Sub offspring. Indeed, PRS increased Sub offspring's serum corticosterone, and exaggerated their anxiety- and depressive-like behavior, while Dom offspring remained resilient to the hormonal and behavioral consequences of PRS. Moreover, PRS exposure markedly facilitated glucocorticoid receptor (GR) recruitment to the hippocampus among Dom mice in response to restraint stress, which may be responsible for their resilience to stressful challenge. These findings suggest proclivity to adaptive or maladaptive prenatal programming of hippocampal GR recruitment to be inheritable and predictable by social dominance or submissiveness.
发育中的胎儿对产前压力高度敏感，这可能改变下丘脑-垂体-肾上腺（HPA）轴的编程，并增加行为障碍的风险。在人类群体中存在着高度的可变性，许多应激妊娠的后代对逆境表现出韧性，而其余的则表现出脆弱性。为了确定在产前逆境的韧性或脆弱性之间起介导作用的生物学基质，我们使抗应激显性（Dom）和应激敏感亚属（Sub）小鼠暴露于轻度产前束缚应激（PRS，在妊娠第 15、16 和 17 天进行 45 分钟）。我们假设 PRS 会以不同的方式改变调节 HPA 轴的边缘区域的产前编程，并影响 Dom 和 Sub 后代。事实上，PRS 增加了 Sub 后代的血清皮质酮，并使它们的焦虑和抑郁样行为加剧，而 Dom 后代对 PRS 的激素和行为后果仍然具有弹性。此外，PRS 暴露明显促进了应激状态下 Dom 小鼠海马中糖皮质激素受体（GR）的募集，这可能是它们对应激挑战具有弹性的原因。这些发现表明，对海马 GR 募集的适应性或不适应性产前编程的倾向是可遗传的，并可通过社会支配地位或顺从性来预测。
