Associations between prenatal exposure to perfluoroalkyl substances, hypomethylation of MEST imprinted gene and birth outcomes

Mei-Sheng Ku; Wen-Chi Pan; Yen-Tsung Huang; Wu-Shiun Hsieh; Yi-Hsiang Hsu; Pau-Chung Chen; Chen-Yu Liu

doi:10.1016/j.envpol.2022.119183

Associations between prenatal exposure to perfluoroalkyl substances, hypomethylation of MEST imprinted gene and birth outcomes

Environ Pollut. 2022 Jul 1:304:119183. doi: 10.1016/j.envpol.2022.119183. Epub 2022 Mar 21.

Authors

Mei-Sheng Ku¹, Wen-Chi Pan², Yen-Tsung Huang³, Wu-Shiun Hsieh⁴, Yi-Hsiang Hsu⁵, Pau-Chung Chen⁶, Chen-Yu Liu⁷

Affiliations

¹ Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
² Institute of Environmental and Occupational Health Sciences, National Yang-Ming University, Taipei, Taiwan.
³ Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
⁴ Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Pediatrics, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.
⁵ Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA, 02131, USA; Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA; Broad Institute of MIT and Harvard, Boston, MA, 02142, USA.
⁶ Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Environmental and Occupational Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
⁷ Institute of Environmental and Occupational Health Sciences, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address: chenyuliu@ntu.edu.tw.

PMID: 35331797
DOI: 10.1016/j.envpol.2022.119183

Abstract

Prenatal perfluoroalkyl substance (PFAS) exposure has been linked to adverse birth outcomes, but the underlying mechanism has yet to be elucidated. DNA methylation changes in mesoderm-specific transcript (MEST) imprinted gene may be a mechanism of the prenatal exposure effects of PFASs on fetal growth. The aim was to investigate the prenatal PFASs exposure effects on DNA methylation changes in MEST imprinted gene involved in fetal growth. Among 486 mother-infant pairs from the Taiwan Birth Panel Study, PFASs and DNA methylation levels at 5 CpG sites of MEST promoter region were measured in cord blood. Univariable and multivariable linear regressions were performed to estimate the associations between prenatal PFAS exposure, MEST DNA methylation levels, and child birth outcomes. Mediation analysis was performed to examine the potential pathway of MEST methylation between PFASs and birth outcomes. We found that higher prenatal perfluorooctyl sulfonate (PFOS) exposure was significantly associated with lower methylation levels at 5 CpG sites of MEST promoter region (an adjusted β range: -1.56, -2.22). Significant negative associations were also found between MEST methylation levels and child birth weight. Furthermore, the associations between PFOS and perfluorooctanoic acid (PFOA) exposure and MEST methylation levels were more profound in girls than in boys. The mediated effect of average MEST methylation level between PFOS exposure and birth weight was 18.3 (95% CI = 2.1, 40.2; p = 0.014). The direct effect of PFOS exposure to birth weight independent to average MEST methylation level was -93.2 (95% CI = -170.5, -17.8; p = 0.018). In conclusion, our results suggest that prenatal PFAS exposure, especially PFOS, is associated with lower methylation levels at MEST promoter region, which not only leverages the role of imprinted gene in ensuring the integrity of fetal growth but also provides a potential mechanism for evaluating the prenatal exposure effect.

Keywords: Birth cohort; DNA methylation; Imprinted gene; MEST; Perfluoroalkyl substances; Prenatal exposure.

MeSH terms

Alkanesulfonates
Alkanesulfonic Acids* / toxicity
Birth Weight
DNA Methylation
Environmental Pollutants* / toxicity
Female
Fluorocarbons* / toxicity
Humans
Infant
Male
Pregnancy
Prenatal Exposure Delayed Effects* / chemically induced

Substances

Alkanesulfonates
Alkanesulfonic Acids
Environmental Pollutants
Fluorocarbons