In support of the placental programming hypothesis: Placental endocrine insufficiency programs atypical behaviour in mothers and their offspring.
In support of the placental programming hypothesis: Placental endocrine insufficiency programs atypical behaviour in mothers and their offspring.
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DOI：
10.1113/ep089916
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发表时间：
2022-05
影响因子：
2.7
通讯作者：
John, Rosalind M.
中科院分区：
文献类型：
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作者：
John, Rosalind M.
本次审查的主题是什么？ 在英国，超过一半的孕妇面临着与母亲怀孕问题增加和子女不良后果有关的逆境，但我们不知道这些关系的机制。 它突出了哪些进步？ 对小鼠的研究证明，由后代中印记基因的遗传操作驱动的胎盘内分泌功能不全可同时驱动胎儿生长受限、母体发育的改变和暴露于不利环境的野生型后代的异常行为。这表明胎盘内分泌功能不全可能导致在人群中观察到的低出生体重、母体抑郁和神经发育障碍的合并症。据估计，产前逆境影响了英国一半以上的怀孕，影响了胎儿的生长，增加了死产、早产和婴儿死亡的机会。除了这些直接和非常明显的问题之外，存活下来的婴儿还承担着无形的负担，即影响人类的一些最常见和最普遍的疾病的风险增加。在子宫内暴露于抑郁和焦虑是与这些不良结果有关的一种逆境，这表明母亲的情绪障碍驱动了这些结果。然而，最近在动物模型中的研究表明，母亲的情绪障碍和对儿童的有害结果可能是相同的潜在胎盘病理学的结果。在这些研究中，暴露于胎盘内分泌功能不全的遗传野生型啮齿动物母亲参与较少的以幼崽为中心的行为和较少的自我照顾。在这种异常环境中长大的遗传野生型啮齿动物后代表现出焦虑样行为增加，雄性后代还表现出认知缺陷和非典型社会行为，并有一些抑郁样症状的证据。这项工作通过实验证实，仅胎盘内分泌功能不全就足以驱动母亲及其后代的非典型行为。虽然有一些数据表明这种现象与人类怀孕有关，但还需要做更多的工作。
What is the topic of this review? More than half of all pregnancies in the UK are exposed to adversity linked to increased problems in pregnancy for mothers and adverse outcomes for their children, but we do not know the mechanism(s) underpinning these relationships. What advances does it highlight? Studies in mice prove that placental endocrine insufficiency driven by genetic manipulation of imprinted genes in the offspring can concurrently drive fetal growth restriction, alterations in maternal caregiving and aberrant behaviour in wild‐type offspring exposed to an adverse environment. This suggests that placental endocrine insufficiency might contribute to the co‐morbidity of low birth weight, maternal depression and neurodevelopmental disorders observed in human populations. Prenatal adversity, which is estimated to impact more than half of all pregnancies in the UK, compromises fetal growth and increases the chances of stillbirth, prematurity and infant mortality. Beyond these immediate and highly visible problems, infants that survive carry the invisible burden of increased risk of some of the most common and pervasive diseases that impact human populations. In utero exposure to depression and anxiety is one adversity that has been linked to these poorer outcomes, suggesting that maternal mood disorders drive the outcomes. However, recent studies in animal models suggest that both the maternal mood disorders and the detrimental outcomes for children could be the result of the same underlying placental pathology. In these studies, genetically wild‐type rodent mothers exposed to placental endocrine insufficiency engaged in less pup‐focused behaviours and less self‐care. Genetically wild‐type rodent offspring raised in this abnormal environment exhibited increased anxiety‐like behaviours, with male offspring additionally exhibiting deficits in cognition and atypical social behaviour, with some evidence of depressive‐like symptoms. This work establishes experimentally that placental endocrine insufficiency alone is sufficient to drive atypical behaviour in both mothers and their offspring. Although there are some data to suggest that this phenomenon is relevant to human pregnancy, considerably more work is required.