Protective and sex-specific effects of moderate dose folic acid supplementation on the placenta following assisted reproduction in mice.

13 In support of our findings, PHLDA2 mRNA and protein expression were also significantly downregulated in term human ART placentas compared with placentas from natural pregnancies and associated with upregulated KCNQ1OT1 mRNA; DNA methylation levels at the KCNQ1OT1 ICR showed a decreasing trend in ART placentas. 89 Furthermore, placentas from mouse embryos cultured from the 1‐cell to blastocyst stage exhibited hypomethylation at Kcnq1ot1 , Peg3 and H19/Igf2 ICRs at E18.5. 73 These results suggest that in humans and mice, ART may interfere with the DNAme maintenance machinery likely during the time of global DNA methylation erasure in preimplantation embryos.

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