First trimester vitamin D status and placental epigenomics in preeclampsia among Northern Plains primiparas.

Aims: As maternal vitamin D status has been associated with preeclampsia, the purpose of this study was to determine variations in DNA methylation patterns and associated protein expression in placental genes regulating vitamin D metabolism.

Main Methods: A convenience sample of 48 pregnant nulliparous women, including 11 later diagnosed with preeclampsia, were recruited in this prospective study. Using a case-control design in two groups of women, we administered a food frequency questionnaire to determine vitamin D dietary intake. Laboratory measures included serum vitamin D levels (25[OH]D), DNA methylation patterns and protein expression in placental genes regulating vitamin D metabolism (1α-hydroxylase, CYP27B1; vitamin D receptor, VDR; retinoid X receptor, RXR) from placental tissue collected at delivery among those diagnosed with preeclampsia and those who remained normotensive throughout pregnancy.

Key Findings: There were no significant differences in vitamin D dietary intake or mean serum 25[OH]D levels, although the proportion of women with deficient 25[OH]D levels was higher in the preeclampsia group (46%) than the normotensive group (20%). Placenta samples from women with preeclampsia also had increased DNA methylation of CYP27B1, VDR and RXR genes with lower protein expression levels limited to RXR.

Significance: Hypermethylation of key placental genes involved in vitamin D metabolism suggests uncoupling of processes that may interfere with placentation and availability of vitamin D at the maternal-fetal interface.