Abstract
BACKGROUND: Fetal exposure to endocrine-disrupting chemicals (EDCs) has been associated with reduced male fecundity, but with few studies considering chemical mixtures. OBJECTIVES: We assessed the association between fetal exposure to a mixture of EDCs and biomarkers of male fecundity in young adulthood. MATERIALS AND METHODS: The study population comprised 841 young adult males enrolled in the Fetal Programming of Semen Quality cohort, established as a male offspring sub-cohort within the Danish National Birth Cohort. Maternal blood samples were analyzed for concentrations of per- and polyfluoroalkyl substances (PFAS), phthalate metabolites, and triclosan. We used quantile g-computation to estimate the change in semen characteristics, testicular volume, and reproductive hormone levels with 95% confidence intervals (CI) per one-quartile increase in all chemicals within three chemical mixtures; an overall chemical mixture, a PFAS mixture, and a non-persistent chemical mixture. RESULTS: Fetal exposure to a one-quartile increase in the overall chemical mixture was associated with 4.0 million/mL lower sperm concentration (95% CI: -9.1, 1.1), 16.1 million lower total sperm count (95% CI: -33.8, 1.6), 0.5 mL smaller testicular volume (95% CI: -1.2, 0.3), 5% higher proportion of non-progressive and immotile spermatozoa (95% CI: 0.99, 1.11), and 7% higher concentration of FSH (95% CI: 0.99, 1.16), but with limited precision. Effect sizes were greatest in magnitude for sperm concentration and total sperm count. We observed somewhat similar associations for the PFAS mixture and no associations for the non-persistent chemical mixture. DISCUSSION: Results suggest that fetal exposure to an overall mixture of EDCs may be adversely associated with several biomarkers of male fecundity, but findings are also compatible with null associations. These associations, if true, appeared to be driven by PFAS, but misclassification due to a single measurement of the phthalate metabolites and triclosan may have attenuated the results.