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Associations among maternal perfluoroalkyl substance levels, fetal sex-hormone enzymatic gene polymorphisms, and fetal sex hormone levels in the Hokkaido study

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Title: Associations among maternal perfluoroalkyl substance levels, fetal sex-hormone enzymatic gene polymorphisms, and fetal sex hormone levels in the Hokkaido study
Authors: Kobayashi, Sumitaka Browse this author →KAKEN DB
Sata, Fumihiro Browse this author
Ikeda-Araki, Atsuko Browse this author →KAKEN DB
Miyashita, Chihiro Browse this author →KAKEN DB
Itoh, Sachiko Browse this author →KAKEN DB
Goudarzi, Houman Browse this author
Iwasaki, Yusuke Browse this author
Mitsui, Takahiko Browse this author
Moriya, Kimihiko Browse this author
Shinohara, Nobuo Browse this author →KAKEN DB
Cho, Kazutoshi Browse this author →KAKEN DB
Kishi, Reiko Browse this author →KAKEN DB
Keywords: Perfluoroalkyl substances
Sex hormone
Gene-environment interaction
Sex difference
Issue Date: Oct-2021
Publisher: Elsevier
Journal Title: Reproductive toxicology
Volume: 105
Start Page: 221
End Page: 231
Publisher DOI: 10.1016/j.reprotox.2021.09.003
Abstract: Prenatal sex hormones affect fetal growth; for example, prenatal exposure to low levels of androgen accelerates female puberty onset. We assessed the association of perfluoroalkyl substances (PFASs) in maternal sera and infant genotypes of genes encoding enzymes involved in sex steroid hormone biosynthesis on cord sera sex hormone levels in a prospective birth cohort study of healthy pregnant Japanese women (n = 224) recruited in Sapporo between July 2002 and October 2005. We analyzed PFAS and five sex hormone levels using liquid chromatography-tandem mass spectrometry. Cytochrome P450 (CYP) 17A1 (CYP17A1 rs743572), 19A1 (CYP19A1 rs10046, rs700519, and rs727479), 3 beta-hydroxysteroid dehydrogenase type 1 (HSD3B1 rs6203), type 2 (HSD3B2 rs1819698, rs2854964, and rs4659175), 17 beta-hydroxysteroid dehydrogenase type 1 (HSD17B1 rs605059, rs676387, and rs2676531), and type 3 (HSD17B3 rs4743709) were analyzed using real-time PCR. Multiple linear regression models were used to establish the influence of log10-transformed PFAS levels and infant genotypes on log10-transformed sex steroid hormone levels. When the interaction between perfluorooctanesulfonate (PFOS) levels and female infant genotype CYP17A1 (rs743572) on the androstenedione (A-dione) levels was considered, the estimated changes (95 % confidence intervals) in A-dione levels against PFOS levels, female infant genotype CYP17A1 (rs743572)-AG/GG, and interaction between them showed a mean increase of 0.445 (0.102, 0.787), mean increase of 0.392 (0.084, 0.707), and mean reduction of 0.579 (0.161, 0.997) (Pint = 0.007), respectively. Moreover, a female-specific interaction with testosterone levels was observed. A-dione and T levels showed positive main effects and negative interaction with PFOS levels and the female infant CYP17A1 genotype.
Rights: © 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:環境健康科学研究教育センター (Center for Environmental and Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 小林 澄貴

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