Methylomic changes in individuals with psychosis, prenatally exposed to endocrine disrupting compounds: Lessons from diethylstilbestrol

作者：Rivollier Fabrice; Chaumette Boris; Bendjemaa Narjes; Chayet Melanie; Millet Bruno; Jaafari Nematollah; Barhdadi Amina; Perreault Louis Philippe Lemieux; Provost Sylvie; Dube Marie Pierre; Gaillard Raphael; Krebs Marie Odile^*; Kebir Oussama

来源：PLos One, 2017, 12(4): e0174783.

DOI：10.1371/journal.pone.0174783

Background
In the Western world, between 1940 and 1970, more than 2 million people were exposed in utero to diethylstilbestrol (DES). In exposed individuals, and in their descendants, adverse outcomes have been linked to such exposure, including cancers, genital malformations, and less consistently, psychiatric disorders. We aimed to explore whether prenatal DES exposure would be associated with DNA methylation changes, and whether these epigenetic modifications would be associated with increased risk of psychosis.
Methods
From 247 individuals born from mothers exposed to DES, we selected 69 siblings from 30 families. In each family, at least one sibling was exposed in utero to DES. We performed a methylome-wide association study using HumanMethylation450 DNA Analysis BeadChip (R) in peripheral blood. We analyzed methylation changes at individual CpGs or regions in exposed (n = 37) versus unexposed individuals (n = 32). We also compared exposed individuals with (n = 7) and without psychosis (n = 30).
Results
There were more individuals with schizophrenia in the DES-exposed group. We found no significant differences between exposed and unexposed individuals with respect to differentially methylated CpGs or regions. The largest difference was in a region near the promoter of an ADAMTS proteoglycanase gene (ADAMTS9). Compared to exposed individuals without psychosis, exposed individuals with psychosis had differential methylation in the region encompassing the gene encoding the zinc finger protein 57 ( ZFP57).
Conclusions
In utero exposure to DES was not associated with methylation changes at specific CpGs or regions. In exposed individuals, however, psychosis was associated with specific methylomic modifications that could impact neurodevelopment and neuroplasticity.

• 出版日期2017-4-13