Association between maternal exposure to di(2-ethylhexyl) phthalate and reproductive hormone levels in fetal blood: The Hokkaido Study on environment and children's health

Atsuko Araki, Takahiko Mitsui, Chihiro Miyashita, Tamie Nakajima, Hisao Naito, Sachiko Ito, Seiko Sasaki, Kazutoshi Cho, Tamiko Ikeno, Katsuya Nonomura, Reiko Kishi

Research output: Contribution to journalArticle

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Abstract

Prenatal di(2-ethylhexyl) phthalate (DEHP) exposure can produce reproductive toxicity in animal models. Only limited data exist from human studies on maternal DEHP exposure and its effects on infants. We aimed to examine the associations between DEHP exposure in utero and reproductive hormone levels in cord blood. Between 2002 and 2005, 514 pregnant women agreed to participate in the Hokkaido Study Sapporo Cohort. Maternal blood samples were taken from 23-35 weeks of gestation and the concentration of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), was measured. Concentrations of infant reproductive hormones including estradiol (E2), total testosterone (T), and progesterone (P4), inhibin B, insulin-like factor 3 (INSL3), steroid hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone were measured from cord blood. Two hundred and two samples with both MEHP and hormones' data were included in statistical analysis. The participants completed a self-administered questionnaire regarding information on maternal characteristics. Gestational age, birth weight and infant sex were obtained from birth records. In an adjusted linear regression analysis fit to all study participants, maternal MEHP levels were found to be associated with reduced levels of T/ E2, P4, and inhibin B. For the stratified analyses for sex, inverse associations between maternal MEHP levels T/E2, P4, inhibin B, and INSL3 were statistically significant for males only. In addition, the MEHP quartile model showed a significant p-value trend for P4, inhibin B, and INSL3 decrease in males. Since inhibin B and INSL3 are major secretory products of Sertoli and Leydig cell, respectively, the results of this study suggest that DEHP exposure in utero may have adverse effects on both Sertoli and Leydig cell development in males, which agrees with the results obtained from animal studies. Comprehensive studies investigating phthalates' exposure in humans, as well as their long-term effects on reproductive development are needed.

Original languageEnglish
Article numbere109039
JournalPloS one
Volume9
Issue number10
DOIs
Publication statusPublished - 08-10-2014

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Maternal Exposure
phthalates
Fetal Blood
Blood
Mothers
hormones
Health
Hormones
Japan
inhibin
blood
Leydig Cells
Sertoli Cells
Animals
Steroid hormones
insulin
Birth Certificates
Globulins
Follicle Stimulating Hormone
Leydig cells

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Araki, Atsuko ; Mitsui, Takahiko ; Miyashita, Chihiro ; Nakajima, Tamie ; Naito, Hisao ; Ito, Sachiko ; Sasaki, Seiko ; Cho, Kazutoshi ; Ikeno, Tamiko ; Nonomura, Katsuya ; Kishi, Reiko. / Association between maternal exposure to di(2-ethylhexyl) phthalate and reproductive hormone levels in fetal blood : The Hokkaido Study on environment and children's health. In: PloS one. 2014 ; Vol. 9, No. 10.
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Association between maternal exposure to di(2-ethylhexyl) phthalate and reproductive hormone levels in fetal blood : The Hokkaido Study on environment and children's health. / Araki, Atsuko; Mitsui, Takahiko; Miyashita, Chihiro; Nakajima, Tamie; Naito, Hisao; Ito, Sachiko; Sasaki, Seiko; Cho, Kazutoshi; Ikeno, Tamiko; Nonomura, Katsuya; Kishi, Reiko.

In: PloS one, Vol. 9, No. 10, e109039, 08.10.2014.

Research output: Contribution to journalArticle

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T1 - Association between maternal exposure to di(2-ethylhexyl) phthalate and reproductive hormone levels in fetal blood

T2 - The Hokkaido Study on environment and children's health

AU - Araki, Atsuko

AU - Mitsui, Takahiko

AU - Miyashita, Chihiro

AU - Nakajima, Tamie

AU - Naito, Hisao

AU - Ito, Sachiko

AU - Sasaki, Seiko

AU - Cho, Kazutoshi

AU - Ikeno, Tamiko

AU - Nonomura, Katsuya

AU - Kishi, Reiko

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