Introduction: Increasing incidence of male reproductive disorders may be due to fetal exposure to putative endocrine disruptor chemicals (EDCs), such as phthalates and phenols. Anogenital Distance (AGD) is a biomarker of fetal androgen action in animals, and has recently been linked to testicular dysgenesis syndrome in humans.
Objective: To examine the relationship between prenatal phthalate and phenol exposure and birth AGD in male infants.
Method: Serum samples were collected from pregnant women between 10 and 12 weeks of gestation as part of a larger prospective study (n=334). 27 EDCs (16 phthalate monoesters, and nine phenols) were measured using liquid chromatography/tandem mass spectrometry. Statistical analyses excluded EDCs detectable in <45% of mothers. Birth AGD in males (measured from centre of anus to base of scrotum) was recorded (n=151).
Results: Six phthalate monoesters (MEP, MiBP, MnBP, MEHP, MECPP, and MCiOP) and three phenols (BPA, TCS, and BP-3) were detectable in ≥45%; median concentrations were 1.57, 3.77, 1.30, 1.17, 0.52, 0.19, 1.78, 0.75 and 0.30 μg/l, respectively. Summed levels were calculated for di(2-ethylhexyl)phthalate metabolites (ΣDEHPm), dibutylphthalate isomer metabolites (ΣMBP(i+n)), and all phthalate metabolites (Σall.phth.m). Mean±S.D. birth AGD was 19.5±5.5 mm. AGD was negatively correlated with ΣDEHPm (ρ=−0.188, P=0.021) and Σall.phth.m (ρ=−0.203, P=0.012), but no other EDCs. In a multiple regression model, potential confounding factors (maternal age, BMI, gestation, birth weight, and birth length) explained 4.5% of variance in birth AGD; entry of EDC levels (MEP, ΣMBP(i+n), ΣDEHPm, MCiOP, BPA, TCS, and BP-3) explained an additional 7.1%. In this model, only ΣDEHPm (β=−0.210, P=0.019) and BMI (β=0.177, P=0.043) were significant. In a separate analysis, Σall.phth.m explained an additional 4.5% of variance in AGD when potential confounders were controlled for (β=−0.213, P=0.014).
Conclusion: These results suggest that exposure to phthalates during the first trimester (specifically DEHP, and possibly others in combination), but not phenols, adversely affects male reproductive development.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology