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Association of exposure to prenatal phthalate esters and bisphenol A and polymorphisms in the ESR1 gene with the second to fourth digit ratio in school-aged children: Data from the Hokkaido study.

Authors
  • Nishimura, Yoko1
  • Moriya, Kimihiko2
  • Kobayashi, Sumitaka3
  • Araki, Atsuko3
  • Sata, Fumihiro4
  • Mitsui, Takahiko5
  • Itoh, Sachiko3
  • Miyashita, Chihiro3
  • Cho, Kazutoshi6
  • Kon, Masafumi7
  • Nakamura, Michiko7
  • Kitta, Takeya8
  • Murai, Sachiyo7
  • Kishi, Reiko3
  • Shinohara, Nobuo7
  • 1 Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo 060-8638, Japan; Center for Environmental and Health Sciences, Hokkaido University, North-12, West-7, Kita-ku, Sapporo 060-0812, Japan. , (Japan)
  • 2 Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo 060-8638, Japan; Department of Urology, Sapporo City General Hospital, North-11, West-13, Chuo-ku, Sapporo 060-8604, Japan. Electronic address: [email protected] , (Japan)
  • 3 Center for Environmental and Health Sciences, Hokkaido University, North-12, West-7, Kita-ku, Sapporo 060-0812, Japan. , (Japan)
  • 4 Center for Environmental and Health Sciences, Hokkaido University, North-12, West-7, Kita-ku, Sapporo 060-0812, Japan; Health Center, Chuo University, 42-8, Ichigaya-Hommura-cho, Shinjuku-ku, Tokyo 162-8473, Japan. , (Japan)
  • 5 Department of Urology, Graduate School of Medical Science, University of Yamanashi, Simokato-1110, Chuo 409-3898, Japan. , (Japan)
  • 6 Maternity and Perinatal Care Center, Hokkaido University Hospital, North-14, West-5 Kita-ku, Sapporo 060-8648, Japan. , (Japan)
  • 7 Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo 060-8638, Japan. , (Japan)
  • 8 Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo 060-8638, Japan. Electronic address: [email protected] , (Japan)
Type
Published Article
Journal
Steroids
Publication Date
Jul 01, 2020
Volume
159
Pages
108637–108637
Identifiers
DOI: 10.1016/j.steroids.2020.108637
PMID: 32165209
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Phthalates and bisphenol A (BPA) are estrogenic endocrine disruptors. Polymorphisms in the gene encoding estrogen receptor 1 (ESR1) may contribute to the ratio of the lengths of the second and fourth digits (2D:4D), which is considered an index of prenatal exposure to sex hormones. Thus, we investigated whether ESR1 polymorphisms modify the effects of prenatal exposure to phthalates and BPA on 2D:4D in a birth cohort. Maternal serum in the first trimester was used to determine prenatal exposure to these compounds. Six hundred twenty-three children (7 years of age) provided mean 2D:4D from photocopies and were genotyped for single nucleotide polymorphisms in ESR1, particularly PvuII (T > C, dbSNP: rs2234693), XbaI (A > G, dbSNP: rs9340799), and rs2077647 (A > G). The associations among compound exposure, mean 2D:4D, and ESR1 polymorphisms were assessed by multiple linear regression adjusted for potential cofounding factors. Boys with the AG/GG genotype at rs2077647 in the group exposed to high levels of mono(2-ethylhexyl) phthalate (MEHP) or Σ Di(2-ethylhexyl) phthalate (DEHP) showed feminized 2D:4D compared with boys with the AA genotype at rs2077647 who had low exposure to MEHP or ΣDEHP (MEHP: increase in mean 2D:4D of 1.51%, 95% confidence interval [CI]: 0.40-2.63; ΣDEHP: increase in mean 2D:4D of 1.37%, 95% CI: 0.25-2.49). No significant differences were found among girls. There were no associations between mean 2D:4D and metabolites other than MEHP or BPA. These data suggest that ESR1 polymorphisms modify the effects of prenatal exposure to DEHP on mean 2D:4D among boys. Copyright © 2020 Elsevier Inc. All rights reserved.

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