Abstract
The placenta is the interface between maternal and fetal circulations, integrating maternal and fetal signals to selectively regulate nutrient, gas, and waste exchange, as well as secrete hormones. In turn, the placenta helps create the in utero environment and control fetal growth and development. The unique epigenetic profile of the human placenta likely reflects its early developmental separation from the fetus proper and its role in mediating maternal–fetal exchange that leaves it open to a range of exogenous exposures in the maternal circulation. In this review, we cover recent advances in DNA methylation in the context of placental function and development, as well as the interaction between the pregnancy and the environment.
Highlights
Establishing a successful pregnancy depends on a complex sequence of interactions between maternal and fetal cells, and their interlocutory signals [1]
The hemochorial human placenta is unique from other primates and model organisms like mice in that trophoblast invasion is more extensive and implantation is interstitial [4]
The placenta differentiates from the extraembryonic trophectoderm, giving rise to villous cytotrophoblasts (VCTs) that can proliferate or fuse to form the multinuclear syncytiotrophoblast (ST) layer, which acts as the barrier between maternal and fetal circulations, and the extra-villous trophoblasts (EVTs), which invade the decidua and remodel maternal
Summary
Establishing a successful pregnancy depends on a complex sequence of interactions between maternal and fetal cells, and their interlocutory signals [1]. Hamada and colleagues [46] performed combined whole-genome bisulfide sequencing and RNA-seq, which identified approximately 1,800 mDMRs in the human placenta, some of which were associated with potential paternal and maternal imprinted genes such as TP53 induced glycolysis regulatory phosphatase (TIGAR), sodium bicarbonate cotransporter 3 (SLC4A7), and zinc finger protein (ZFP90) The function of these imprinted genes in placenta or fetal development, remains to be elucidated. The overall level of placental tissue DNA methylation increases over gestation, as does the level of interindividual variation between placentas, potentially indicative of a response to a myriad of environmental exposures and stochastic events, or with a transition and variation in cell composition over time [24] Many of these studies take the form of epigenome-wide association studies (EWAS), and generally use the Infinium HumanMethylation arrays [52, 53]. Study Exposure [99] Cadmium [100] GDM [101] Polybrominated diphenyl ethers, assessed in cord blood [102] Arsenic [103] POPs [104] Proximity to major roadways [105] Maternal prepregnancy obesity [106] Particulate air pollution [107] A range of self-reported exposures [108] Vitamin C and maternal smoking
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