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.
Highlights
Diesters of phthalic acid have been used as plasticizers for various plastic compounds, such as toys, food containers, furniture, personal care products, medical devices, and housing materials
Di(2-ethylhexyl) phthalate (DEHP) is one of the major phthalate compounds and constitutes more than 50% of the phthalates used in production in Japan [5]
Animal studies have shown that fetal exposure to DEHP may induce abnormalities in the reproductive system, reduce testosterone (T) and insulin-like factor 3 (INSL3) levels, and cause disruption to Leydig and Sertoli cell maturation [7,8,9,10]
Summary
Diesters of phthalic acid (phthalates) have been used as plasticizers for various plastic compounds, such as toys, food containers, furniture, personal care products, medical devices, and housing materials. Phthalates are not chemically bonded to polyvinyl chloride (PVC) in plastic products and, as a result, they can leach and migrate into the air, foodstuffs, and other materials. Humans are constantly exposed to phthalates and biomonitoring studies have shown the widespread exposure of the general population to these chemicals [1,2,3,4]. Phthalates are known to exert endocrine-disrupting effects, which have been the cause of some concern [6]. Animal studies have shown that fetal exposure to DEHP may induce abnormalities in the reproductive system, reduce testosterone (T) and insulin-like factor 3 (INSL3) levels, and cause disruption to Leydig and Sertoli cell maturation [7,8,9,10]
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