Maternal stress in pregnancy programs endocrine function and behaviour in offspring

本研究旨在探讨孕期母体应激对子代下丘脑-垂体-肾上腺(HPA；Stress Axis)功能及相关行为的长期影响。急性和慢性应激发生在野生和家养动物种群中。这可能是由于集约化畜牧业、运输、捕食增加或食物供应有限造成的。根据压力的严重程度，压力会对成年人群的健康和寿命产生直接影响，但我们现在有证据表明，它也会对发育中的胎儿和后代产生长期影响。在我们目前由NSERC资助的研究中，我们已经表明，母亲的压力时期可以深刻地改变年轻和成年后代的压力反应和相关行为。此外，这些影响高度依赖于怀孕期间经历压力的时间和后代的性别。我们现在希望扩展我们的研究，以确定参与编程成年HPA功能和行为的中央分子机制，在豚鼠中，像大多数家养物种一样，生下成熟的幼崽。我们也有初步证据表明，产前应激的影响可以传递给多代人，我们将进一步调查这一点。在成年后代中，应激激素释放的调节可以在胎儿时期由母亲所处的环境来编程，这一事实对动物生产和野生动物种群的管理都有巨大的影响。例如，调整一生中应激相关激素的调节可以导致免疫功能和生长的改变，以及葡萄糖稳态、心血管调节和行为的改变。这也可能对生殖能力产生影响。这一提议产生的新信息将增加我们对发展的基本理解。它还将有助于未来的家畜管理(即最大限度地发挥生产潜力)和野生动物种群的管理。

The objective of this research program is to establish the long-term impact of maternal stress during pregnancy on hypothalamic-pituitary-adrenal (HPA; stress axis) function and related behaviours in offspring across multiple generations. Acute and chronic stress occurs in wild and domestic animal populations. This may arise from intensive husbandry, transportation, increased predation or limited food availability. Stress, depending on its severity, will have an immediate impact on the health and longevity of the adult population, but we now have evidence that it will also have a long-term impact on the developing fetus and offspring. During our current NSERC-funded studies we have shown that periods of maternal stress can profoundly alter stress responsiveness and related behaviours in young and adult offspring. Furthermore, these effects are highly dependent on the time in pregnancy at which stress is experienced and the sex of the offspring. We now wish to extend our studies to identify the central molecular mechanisms involved in programming of adult HPA function and behaviour, in the guinea pig which like the majority of domestic species, gives birth to mature young. We also have preliminary evidence that the effects of prenatal stress can be transmitted across multiple generations, and we will investigate this further. The fact that regulation of stress hormone release in adult offspring can be programmed during fetal life, by the environment to which the mother is exposed, has tremendous implications for animal production but also for the management of wild animal populations. For example, modified regulation of stress-related hormones throughout life can lead to altered immune function and growth, as well as modified glucose homeostasis, cardiovascular regulation and behavior. There may also be influences on reproductive capacity. The new information generated by this proposal will increase our fundamental understanding of development. It will also aid in future domestic animal management (i.e. maximizing production potential), and in the management of wild animal populations.