Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta

• Few epidemiologic studies have analyzed effects of mixtures of hormonally active compounds.
• We measured a biomarker of prenatal cumulative exposure to xenoestrogens.
• We examined its relationship with DNA methylation of repetitive elements in placenta.
• Higher levels of xenoestrogens were associated with lower AluYb8 methylation in boys.

BackgroundPrenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks.ObjectivesIn this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation.MethodsThe biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retroviruses (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated.ResultsA significant sex interaction was observed for AluYb8 (p-value for interaction < 0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p-value < 0.001), while no significant effects were found in girls (p-value = 0.134).ConclusionsOur findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development.