The placental programming hypothesis: Placental endocrine insufficiency and the co-occurrence of low birth weight and maternal mood disorders
The placental programming hypothesis: Placental endocrine insufficiency and the co-occurrence of low birth weight and maternal mood disorders
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DOI：
10.1016/j.placenta.2020.03.011
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发表时间：
2020-09-01
期刊：
影响因子：
3.8
通讯作者：
John, R. M.
中科院分区：
文献类型：
--
作者：
Creeth, H. D. J.;John, R. M.
多肽激素和类固醇激素，无论是由胎盘表达还是依赖于胎盘合成，都是在怀孕期间驱动母亲适应支持子宫内生长的关键。这些适应包括在怀孕期间和分娩后改变母亲的行为，以确保后代得到适当的照顾和营养。与啮齿类动物的母体生殖编程有关的胎盘源性激素包括催乳素相关激素和类固醇激素。胎盘产生的神经调质可能直接作用于胎儿，以支持大脑发育。许多印记基因在胎盘中起拮抗作用，以调节表达这些激素的关键胎盘内分泌谱系的发育。正常母系表达基因Phlda2的表达增加或正常父系表达基因Peg3的功能丧失导致胎盘中的内分泌细胞减少，并且幼崽出生时体重较低。重要的是，携带这些基因改变的幼崽的野生型母鼠表现出行为的改变，减少了对养育的关注（Phlda2）或增加了焦虑（Peg3）。这些相同的基因可能会调节人类怀孕期间的胎盘激素，并有可能影响出生体重和母亲的情绪。因此，胎盘中印迹基因的异常表达可能是低出生体重与母亲产前抑郁症共同发生的基础。
Polypeptide hormones and steroid hormones, either expressed by the placenta or dependant on the placenta for their synthesis, are key to driving adaptations in the mother during pregnancy that support growth in utero. These adaptations include changes in maternal behaviour that take place in pregnancy and after the birth to ensure that offspring receive appropriate care and nutrition. Placentally-derived hormones implicated in the programming of maternal caregiving in rodents include prolactin-related hormones and steroid hormones. Neuromodulators produced by the placenta may act directly on the fetus to support brain development. A number of imprinted genes function antagonistically in the placenta to regulate the development of key placental endocrine lineages expressing these hormones. Gain-in-expression of the normally maternally expressed gene Phlda2 or loss-of-function of the normally paternally expressed gene Peg3 results in fewer endocrine cells in the placenta, and pups are born low birth weight. Importantly, wild type dams carrying these genetically altered pups display alterations in their behaviour with decreased focus on nurturing (Phlda2) or heightened anxiety (Peg3). These same genes may regulate placental hormones in human pregnancies, with the potential to influence birth weight and maternal mood. Consequently, the aberrant expression of imprinted genes in the placenta may underlie the reported co-occurrence of low birth weight with maternal prenatal depression.