Maternal Exposure to Per- and Polyfluoroalkyl Substances (PFAS) and Male Reproductive Function in Young Adulthood: Combined Exposure to Seven PFAS

By Katia Keglberg Hærvig, Kajsa Ugelvig Petersen, Karin Sørig Hougaard, Christian Lindh, Cecilia Høst Ramlau-Hansen, Gunnar Toft, Aleksander Giwercman, Birgit Bjerre Høyer, Esben Meulengracht Flachs, Jens Peter Bonde, and Sandra Søgaard Tøttenborg
Environ Health Perspect
October 5, 2022
DOI: 10.1289/EHP10285

Background

Concerns remain about the human reproductive toxicity of the widespread per- and polyfluoroalkyl substances (PFAS) during early stages of development.

Objectives

We examined associations between maternal plasma PFAS levels during early pregnancy and male offspring reproductive function in adulthood.

Methods

The study included 864 young men (age range:18.9-21.2 y) from the Fetal Programming of Semen Quality (FEPOS) cohort established between 2017 and 2019. Plasma samples from their mothers, primarily from the first trimester, were retrieved from the Danish National Biobank and levels of 15 PFAS were measured. Seven PFAS had detectable levels above the limit of detection in of the samples and were included in analyses. Semen quality, testicular volume, and levels of reproductive hormones and PFAS were assessed in the young men. We used weighted quantile sum (WQS) regression to estimate the associations between combined exposure to maternal PFAS and reproductive function, and negative binomial regression to estimate the associations of single substances, while adjusting for a range of -defined fetal and postnatal risk factors.

Results

By a 1-unit increase in the WQS index, combined maternal PFAS exposure was associated with lower sperm concentration (; 95% CI: , ), total sperm count (; 95% CI: , ), and a higher proportion of nonprogressive and immotile sperm (5%; 95% CI: 1%, 8%) in the young men. Different PFAS contributed to the associations with varying strengths; however, perfluoroheptanoic acid was identified as the main contributor in the analyses of all three outcomes despite the low concentration. We saw no clear association between exposure to maternal PFAS and testicular volume or reproductive hormones.

Discussion

In a sample of young men from the general Danish population, we observed consistent inverse associations between exposure to maternal PFAS and semen quality. The study needs to be replicated in other populations, taking combined exposure, as well as emerging short-chain PFAS, into consideration.

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