Centre for Discovery Brain Sciences, Hugh Robson Building, University of Edinburgh, George Square, Edinburgh EH8 9XD, UK.
Zhejiang University-University of Edinburgh Joint Institute, Haining, Zhejiang 314400, P.R. China.
J Exp Biol. 2024 Mar 7;227(Suppl_1). doi: 10.1242/jeb.246073.
Prenatal stress programmes long-lasting neuroendocrine and behavioural changes in the offspring. Often this programming is maladaptive and sex specific. For example, using a rat model of maternal social stress in late pregnancy, we have demonstrated that adult prenatally stressed male, but not prenatally stressed female offspring display heightened anxiety-like behaviour, whereas both sexes show hyperactive hypothalamo-pituitary-adrenal (HPA) axis responses to stress. Here, we review the current knowledge of the mechanisms underpinning dysregulated HPA axis responses, including evidence supporting a role for reduced neurosteroid-mediated GABAergic inhibitory signalling in the brains of prenatally stressed offspring. How maternal psychosocial stress is signalled from the mother to the fetuses is unclear. Direct transfer of maternal glucocorticoids to the fetuses is often considered to mediate the programming effects of maternal stress on the offspring. However, protective mechanisms including attenuated maternal stress responses and placental 11β-hydroxysteroid dehydrogenase-2 (which inactivates glucocorticoids) should limit materno-fetal glucocorticoid transfer during pregnancy. Moreover, a lack of correlation between maternal stress, circulating maternal glucocorticoid levels and circulating fetal glucocorticoid levels is reported in several studies and across different species. Therefore, here we interrogate the evidence for a role for maternal glucocorticoids in mediating the effects of maternal stress on the offspring and consider the evidence for alternative mechanisms, including an indirect role for glucocorticoids and the contribution of changes in the placenta in signalling the stress status of the mother to the fetus.
产前应激会导致后代的神经内分泌和行为长期变化。这种编程通常是适应不良的，并且具有性别特异性。例如，我们使用妊娠晚期母体社交应激的大鼠模型，证明了成年期产前应激的雄性后代而非产前应激的雌性后代表现出焦虑样行为增加，而两性对压力的下丘脑-垂体-肾上腺（HPA）轴反应均增强。在这里，我们回顾了失调的 HPA 轴反应的潜在机制的现有知识，包括支持神经甾体介导的 GABA 能抑制信号在产前应激后代大脑中作用的证据。母体心理社会应激如何从母亲传递到胎儿尚不清楚。母体糖皮质激素向胎儿的直接转移通常被认为介导了母体应激对后代的编程效应。然而，包括减弱的母体应激反应和胎盘 11β-羟类固醇脱氢酶-2（使糖皮质激素失活）在内的保护机制应限制妊娠期间母胎糖皮质激素的转移。此外，在几项研究和不同物种中，都有报道称母体应激、循环母体糖皮质激素水平和循环胎儿糖皮质激素水平之间缺乏相关性。因此，在这里我们探讨了母体糖皮质激素在介导母体应激对后代的影响中的作用的证据，并考虑了替代机制的证据，包括糖皮质激素的间接作用以及胎盘变化在向胎儿传递母体应激状态中的作用。
