Introduction: Environmental exposure during fetal life may disrupt testicular development. In humans, a limited number of studies have investigated whether these adverse effects persist into adulthood. Using data from a prospective, population-based birth cohort study, The Copenhagen Mother-Child cohort, the objective was to assess if there is an association between fetal exposure to selected phenols and benzophenones and markers of testicular function in adult men.

Methods: Pregnant women were recruited in 1997-2001. Their sons were examined clinically at 18-20 years of age, with focus on adult markers of reproductive function (anogenital distance (AGD), semen quality and reproductive hormones). In total, 101 18-20-year-old men were included, whose mothers during pregnancy had a serum sample drawn and analyzed for bisphenol A (BPA) and seven other simple phenols, as well as six benzophenones. To investigate the association between chemical levels (in tertiles, T1-T3) in relation to markers of reproductive function, univariate and multiple linear regression analyses were performed.

Results: In fully adjusted analyses, increased levels of luteinizing hormone (LH) were observed with higher fetal exposure to BPA (percentage difference (95%CI)) (T2: 12% (-8%,36%) and T3: 33% (10%,62%), compared to T1) and benzophenone-3 (BP-3) (T2: 21% (-2%,49%), T3: 18% (-4%,45%)), while no clear association was seen to total testosterone (TT). Higher levels of BPA and BP-3 were associated with a lower TT/LH ratio, although only significant for BPA (p-trend=0.01). No associations were seen to AGD or markers of semen quality.

Conclusion: In conclusion, high exposure to BPA and BP-3 was associated with a compensated reduced Leydig cell function but no other changes in markers of reproductive health. As maternal levels of BPA and BP-3 were not correlated, separate effects may be at play. Larger studies on long-term reproductive consequences of prenatal exposures are warranted to validate our findings.