Associations between Prenatal Exposure to Perfluoroalkyl Substances, Hypomethylation of MEST Imprinted Gene and Birth Outcomes

In utero perfluoroalkyl substances (PFASs) exposures have been linked to adverse birth outcomes, but the underlying mechanism remains elusive. Epigenetic regulations such as changes in DNA methylation profiles in mesoderm-specific transcript (MEST) imprinted gene may provide a potential mechanism of the prenatal exposure effects of PFASs on fetal growth. The aim of the study was to investigate the prenatal exposure effects of PFASs to DNA methylation changes at MEST imprinted gene involved in fetal growth. A total of four hundred and eighty-six mother-infant pairs were included in the analyses from Taiwan Birth Panel Study (TBPS), collecting from 2004 to 2005 in four hospitals in Taipei city and New Taipei City. PFASs were measured by UPLC-MS/MS in cord blood. DNA methylation levels of MEST gene were measured from cord blood. Univariable and multivariable linear regressions were performed to estimate the associations between prenatal PFASs exposures, MEST DNA methylation levels, and the child birth outcomes. Mediation analysis was performed to examine the potential pathway of MEST methylation in the relationship between PFASs and birth outcomes. We found that higher prenatal exposures to perfluorooctyl sulfonate (PFOS) was significantly associated with lower methylation levels at 5 CpG sites of MEST promoter region, after considering potential confounding factors. Significant negative associations were also found between MEST methylation levels and child birth weight. Gender difference was observed in the association between PFASs exposure and MEST methylation level. Prenatal PFOS exposure effect on birth weight might be mediated by MEST methylation. In conclusion, our results suggest that prenatal PFASs exposures, especially PFOS, are associated with lower methylation levels at MEST promoter region, which not only leverage the role of imprinted gene for ensuring the integrity of fetal growth but also provide a potential mechanism for evaluating the prenatal exposure effect. Funding Information: This work was supported by the National Taiwan University Higher Education Sprout Project (NTU-110L8810) within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) and the Ministry of Science and Technology (MOST 103-2633-B-002-013-, MOST 104-2633-B-002-007-) in Taiwan. Declaration of Interests: The authors declare they have no actual or potential competing financial interests. Ethics Approval Statement: Ethical approval of the study was obtained from the Independent Ethics Committee of National Taiwan University Hospital. Informed consent from the pregnant women was obtained before giving birth.