title: 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.
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.
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Araki
authors.affiliation: Department of Urology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Mitsui
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Miyashita
authors.affiliation: Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan.
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Graduate School of Medicine, Nagoya University, Nagoya, Aichi, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Naito
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Public Health, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Department of Obstetrics and Genecology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Cho
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Tamiko
authors.initials: T
authors.lastname: Ikeno
authors.affiliation: Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Nonomura
authors.affiliation: Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kishi
mesh_terms: D000328:Adult; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D004781:Environmental Exposure; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D006801:Humans; D007265:Inhibins / Q000097:blood; D007328:Insulin / Q000096:biosynthesis; D007986:Luteinizing Hormone / Q000097:blood; D018811:Maternal Exposure / Q000009:adverse effects*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D011506:Proteins; D013739:Testosterone / Q000097:blood
chemical_list: D007328:Insulin; C084797:Leydig insulin-like protein; D011506:Proteins; C422364:inhibin B; D013739:Testosterone; D011374:Progesterone; D007265:Inhibins; D007986:Luteinizing Hormone; D004051:Diethylhexyl Phthalate