Sex-linked placental DNA methylation associated with early-onset preeclampsia.

Impaired placental development and function is a necessary feature of early-onset preeclampsia (EOPE), a severe pregnancy complication. We do not fully understand the molecular changes underlying EOPE; however, we know that DNA methylation, a chemical mark on DNA, can be measured to identify changes associated with EOPE. Typically, human cells have 22 pairs of autosomal chromosomes and one pair of sex chromosomes; females have two X chromosomes (XX) and males one X and one Y chromosome (XY). This is the first study to investigate and identify an association between EOPE and X and Y chromosome DNA methylation in the placenta. We used DNA methylation data from 843 placentas (XX = 386, XY = 457). We identified differences in X and Y chromosome DNA methylation associated with EOPE-pathology. Most differences in DNA methylation were observed in both males and females. Some of the associations were in genes which may have relevance to the pathophysiology of EOPE in the placenta. Our study highlights that there are important findings on the X and Y chromosomes that have been missed by their routine exclusion in previous studies.