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Effects of prenatal perfluoroalkyl acid exposure on cord blood IGF2/H19 methylation and ponderal index: The Hokkaido Study

Journal of Exposure Science & Environmental Epidemiology volume 27, pages 251–259 (2017)Cite this article

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Abstract

Prenatal exposure to perfluoroalkyl acids (PFAAs) influences fetal growth and long-term health. However, whether PFAAs affect offspring DNA methylation patterns to influence health outcomes is yet to be evaluated. Here, we assessed effect of prenatal PFAA exposure on cord blood insulin-like growth factor 2 (IGF2), H19, and long interspersed element 1 (LINE1) methylation and its associations with birth size. Mother–child pairs (N=177) from the Hokkaido Study on Environment and Children’s Health were included in the study. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) levels in maternal serum were measured by liquid chromatography-tandem mass spectrometry. IGF2, H19, and LINE1 methylation in cord blood DNA was determined by pyrosequencing. After full adjustment in multiple linear regression models, IGF2 methylation showed a significant negative association with log-unit increase in PFOA (partial regression coefficient=−0.73; 95% confidence interval: −1.44 to −0.02). Mediation analysis suggested that reduced IGF2 methylation explained ~21% of the observed association between PFOA exposure and reduced ponderal index of the infant at birth. These results indicated that the effects of prenatal PFOA exposure could be mediated through DNA methylation. Further study will be required to determine the potential for long-term adverse health effects of reduced IGF2 methylation induced by PFOA exposure.

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Acknowledgements

We thank the staff at Sapporo Toho Hospital and the participating mothers and infants for their collaboration. We also thank YM Ito for advice on statistical analyses, TA Yila for advice on epigenetics, and R Ito and Y Iwasaki for PFAA measurements. This study was supported by a Grant-in-Aid for Health Science Research from the Japanese Ministry of Health, Labor and Welfare (No. 717L00204) and by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology (Nos. 23390157 and 25253050). We also thank Editage (www.editage.jp) for English language editing.

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Authors and Affiliations

  1. Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan

    Sachiko Kobayashi, Kaoru Azumi, Houman Goudarzi, Atsuko Araki, Chihiro Miyashita, Sumitaka Kobayashi, Sachiko Itoh, Tamiko Ikeno & Reiko Kishi

  2. Department of Public Health Sciences, Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Seiko Sasaki

  3. Department of Environmental Veterinary Sciences, Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan

    Mayumi Ishizuka

  4. Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan

    Hiroyuki Nakazawa

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  1. Sachiko Kobayashi
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Correspondence to Reiko Kishi.

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Kobayashi, S., Azumi, K., Goudarzi, H. et al. Effects of prenatal perfluoroalkyl acid exposure on cord blood IGF2/H19 methylation and ponderal index: The Hokkaido Study. J Expo Sci Environ Epidemiol 27, 251–259 (2017). https://doi.org/10.1038/jes.2016.50

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