BACKGROUND: In utero exposure to xenostrogens may modify the epigenome. We explored the association of prenatal exposure to mixtures of xenoestrogens and genome-wide placental DNA methylation. MATERIALS & METHODS: Sex-specific associations between methylation changes in placental DNA by doubling the concentration of TEXB-alpha exposure were evaluated by robust multiple linear regression. Two CpG sites were selected for validation and replication in additional male born placentas. RESULTS: No significant associations were found, although the top significant CpGs in boys were located in the LRPAP1, HAGH, PPARGC1B, KCNQ1 and KCNQ1DN genes, previously associated to birth weight, Type 2 diabetes, obesity or steroid hormone signaling. Neither technical validation nor biological replication of the results was found in boys for LRPAP and PPARGC1B. CONCLUSION: Some suggestive genes were differentially methylated in boys in relation to prenatal xenoestrogen exposure, but our initial findings could not be validated or replicated.

This work was part of the European-wide project Transportation Air pollution and Physical ActivitieS (TAPAS): an integrated health risk assessment program of climate change and urban policies, which had partners in Barcelona, Basel, Copenhagen, Paris, Prague, and Warsaw. TAPAS was a 4-year project funded by the Coca-Cola Foundation, AGAUR, and CREAL (http://www.tapas-program.org/). CREAL is part of CIBERESP (http://www.ciberesp.es/), the Spanish Network for Epidemiology and Public Health Research. CREAL and its members are based at and supported by the Universitat Pompeu Fabra (http://www.upf.edu/en/).