Prenatal di(2-ethylhexyl) phthalate exposure and disruption of adrenal androgens and glucocorticoids levels in cord blood: The Hokkaido Study

•Epidemiological studies of DEHP exposure on adrenal androgen and glucocorticoid disruption are limited.•Associations between maternal blood MEHP level and fetal adrenal androgen and glucocorticoids in cord blood were examined.•Prenatal DEHP exposure was associated with changes in adrenal androgen and glucocorticoid levels at birth.•Even relatively low level of DEHP that humans are exposed has altered steroid hormone profiles of fetus at birth.

Di(2-ethylhexyl) phthalate (DEHP) is known for its endocrine disrupting properties. We previously demonstrated that prenatal DEHP exposure is associated with decreased progesterone levels and testosterone/estradiol ratio in the cord blood. However, evidence of the effects of prenatal DEHP exposure on adrenal androgen and glucocorticoids in infants is scarce. Thus, the objectives of this study were to investigate the association between prenatal DEHP exposure and adrenal androgen and glucocorticoids, and to discuss its effects on steroid hormone profiles in infants. This is part of a birth cohort study: The Hokkaido Study on Environment and Children's Health, Sapporo Cohort. Among the 514 participants, 202 mother-infant pairs with available data on maternal mono(2-ethylhexyl) phthalate (MEHP), adrenal androgen (dehydroepiandrostenedione [DHEA] and androstenedione) and glucocorticoid (cortisol and cortisone) cord blood levels were included in this study. After adjusting for potential confounders, a linear regression analysis showed that maternal MEHP levels were associated with reduced cortisol and cortisone levels and glucocorticoid/adrenal androgen ratio, whereas increased DHEA levels and DHEA/androstenedione ratio. In a quartile model, when comparing the adjusted least square means in the 4th quartile of MEHP with those in the 1st quartile, cortisol and cortisone levels and glucocorticoid/adrenal androgen ratio decreased, whereas DHEA/androstenedione and cortisol/cortisone ratios increased. Significant p-value trends for cortisol and cortisone levels, cortisol/cortisone ratio, and glucocorticoid/adrenal androgen ratio were observed. In combination with the previous results of reduced progesterone levels and testosterone/estradiol ratio, prenatal exposure to DEHP altered the steroid hormone profiles of infants. Further studies investigating the long-term effects of DEHP exposure on growth, neurodevelopment, and gonad and reproductive function are required.

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