Associations of prenatal exposure to multiple metals with testicular volume and anogenital distance in infant boys: A longitudinal cohort study

Background: Human are widely exposed to multiple metals, some of which have suspected reproductive toxicity, but no human studies have investigated the developmental effects of prenatal metal exposure. Objectives: We aimed to evaluate the associations between prenatal multiple metal exposure and reproductive development in boys at 2-3 years using multi-pollutant approach. Methods: This prospective study used data of 564 mother-child pairs recruited from the Guangxi Birth Cohort Study. Twenty serum metal concentrations were measured. Least absolute shrinkage and selection operator (LASSO) penalized regression was used to identify independent associations between prenatal multiple metal exposure and testicular volume (TV), and anogenital distance (AGD). Adjusted estimates were then obtained using multiple linear regression analysis, and the regression tree method was used to explore the interactions. Results: Boys in the highest quartile of prenatal lead exposure had a 0.064 mL (95% CI: -0.124, -0.004) smaller ln-transformed TV, 0.060 cm (95% CI: -0.110, -0.011) shorter ln-transformed anopenile distance (AGDap), and 0.115 cm (95% CI: -0.190, -0.039) shorter ln-transformed anoscrotal distance (AGDas) than boys in the lowest quartile (all Ptrend < 0.05). Chromium was inversely with ln-transformed AGDap (beta = -0.078, 95% CI: -0.127, -0.030) and ln-transformed AGDas (beta = -0.113, 95% CI: -0.188, -0.038), while stibium was positivity associated with ln-transformed AGDap (beta = 0.091, 95% CI: 0.046, 0.136) and strontium was positivity associated with ln-transformed AGDas (beta = 0.120, 95% CI: 0.051, 0.189) (all Ptrend < 0.05). And the critical window of vulnerability may be the late pregnancy (the second and third trimester). Moreover, we detected interaction effects between lead, chromium and stibium on AGDap; lead, chromium and strontium on AGDas. Conclusions: The results suggest that prenatal exposure to lead, chromium, stibium and strontium may affect TV and/or AGD in infant boys. Potential mechanisms for the complex metal interactive effects during vulnerable periods are worthy of further investigation.