Division of Neurobiology, The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush Campus, Midlothian, Scotland EH25 9RG, UK.
Reproduction. 2013 Oct 1;146(5):R175-89. doi: 10.1530/REP-13-0258. Print 2013.
A suboptimal in utero environment, for example, as a result of maternal stress, can have detrimental effects on the pregnancy and long-term adverse 'programming' effects on the offspring. This article focuses on the effects of prenatal social stress on the mother, her pregnancy and the offspring, since these issues have ethological relevance in both animals and humans. The consequences of social stress exposure depend on when during pregnancy the stress occurs, and many of the effects on the offspring are sex specific. Social stress during early pregnancy tends to result in pregnancy loss, whereas stress exposure later in pregnancy, when the mother has already invested considerable resources in the foetuses, results in programmed offspring of low birth weight: a risk factor for various adulthood diseases. Neuroendocrine and behavioural responses to stress in the offspring are particularly sensitive to foetal programming by prenatal stress, indicated by enhanced hypothalamo-pituitary-adrenal (HPA) axis responses and increased anxiety behaviour, which result from permanent changes in the offspring's brain. The dysregulation of HPA axis function may also interfere with other systems, for example, the hypothalamic-pituitary-gonadal axis, as there is evidence for alterations in steroidogenesis, reproductive potential and impaired reproductive/social behaviours in prenatally stressed offspring. Prenatal social stress also programmes future maternal behaviour, highlighting the potential for negative phenotypes to be transmitted to future generations. The possible mechanisms through which maternal stress during pregnancy is transmitted to the foetuses and the foetal brain is programmed by prenatal stress and the potential to overwrite programming of the offspring are discussed.
例如,宫内环境不佳(例如,由于母体压力)会对妊娠产生不利影响,并对后代产生长期的不利“编程”影响。本文重点关注产前社会压力对母亲、她的怀孕和后代的影响,因为这些问题在动物和人类中都具有进化生物学意义。社会压力暴露的后果取决于压力发生在怀孕期间的哪个阶段,并且许多对后代的影响是性别特异性的。早孕期间的社会压力往往会导致妊娠丢失,而妊娠后期(此时母亲已经为胎儿投入了大量资源)的压力暴露会导致出生体重低的编程后代:这是各种成年疾病的危险因素。后代对压力的神经内分泌和行为反应特别容易受到产前压力的胎儿编程的影响,表现为下丘脑-垂体-肾上腺 (HPA) 轴反应增强和焦虑行为增加,这是由于后代大脑发生永久性变化所致。HPA 轴功能的失调也可能干扰其他系统,例如下丘脑-垂体-性腺轴,因为有证据表明产前应激的后代中类固醇生成、生殖潜力和受损的生殖/社交行为发生改变。产前社会压力还会对未来的母亲行为进行编程,突出了将负面表型传递给后代的可能性。讨论了怀孕期间母体压力传递给胎儿以及产前压力对胎儿大脑进行编程的可能机制,以及重写后代编程的潜力。