An Altered DNA Methylation Status in the Human Umbilical Cord Is Correlated with Maternal Exposure to Polychlorinated Biphenyls

Akifumi Eguchi,Hiromi Tanabe,Hidenobu Miyaso,Atsushi Kaneda,Kenichi Sakurai,Bahityar Rahmutulla,Emiko Todaka,Shino Nishizawa-Jotaki,Masahiro Watanabe,Chisato Mori

doi:10.3390/ijerph16152786

Abstract

Maternal exposure to polychlorinated biphenyls (PCBs) results in abnormal fetal development, possibly because of epigenetic alterations. However, the association between PCB levels in cord serum with fetal DNA methylation status in cord tissue is unclear. This study aims to identify alterations in DNA methylation in cord tissue potentially associated with PCB levels in cord serum from a birth cohort in Chiba, Japan (male neonates = 32, female neonates = 43). Methylation array analysis identified five sites for female neonates (cg09878117, cg06154002, cg06289566, cg12838902, cg01083397) and one site for male neonates (cg13368805) that demonstrated a change in the methylation degree. This result was validated by pyrosequencing analysis, showing that cg06154002 (tudor domain containing 9: TDRD9) in cord tissue from female neonates is significantly correlated with total PCB levels in cord serum. These results indicate that exposure to PCBs may alter TDRD9 methylation levels, although this hypothesis requires further validation using data obtained from female neonates. However, since the present cohort is small, further studies with larger cohorts are required to obtain more data on the effects of PCB exposure and to identify corresponding biomarkers.

Highlights

Undernutrition during gestation and early childhood is suggested to increase the risk of cardiovascular diseases in adulthood [1]; the “Developmental origins of health and disease” (DOHaD) concept has been postulated [2]
Persistent organic pollutants including polychlorinated biphenyls (PCBs) may affect DNA methylation, necessitating new risk assessment methods focusing on epigenetic alterations [9]
There were no significant differences in total PCB levels (Male: Female, 72 [interquartile range, IQR: 52–120] and 66 [IQR: 44–100] pg/g wet, respectively), body weight at birth, and maternal characteristics between the male and female neonates (Tables 1 and 2)

Summary

Introduction

Undernutrition during gestation and early childhood is suggested to increase the risk of cardiovascular diseases in adulthood [1]; the “Developmental origins of health and disease” (DOHaD) concept has been postulated [2]. Epigenetic modifications during fetal development and childhood are potentially associated with lifestyle-related diseases in adults, indicating that the DOHaD paradigm may have an epigenetic mechanistic basis [4,5]. Exposure to persistent organic pollutants (POPs) was reported to be associated with global DNA hypomethylation in Greenland Inuit and healthy Korean populations [6,7,8]. Persistent organic pollutants including polychlorinated biphenyls (PCBs) may affect DNA methylation, necessitating new risk assessment methods focusing on epigenetic alterations [9].

Objectives

Methods

Conclusion