TY - JOUR

T1 - Maternal Exposure to Per- and Polyfluoroalkyl Substances (PFAS) and Male Reproductive Function in Young Adulthood

T2 - Combined Exposure to Seven PFAS

AU - Haervig, Katia Keglberg

AU - Petersen, Kajsa Ugelvig

AU - Hougaard, Karin Sorig

AU - Lindh, Christian

AU - Ramlau-Hansen, Cecilia Host

AU - Toft, Gunnar

AU - Giwercman, Aleksander

AU - Hoyer, Birgit Bjerre

AU - Flachs, Esben Meulengracht

AU - Bonde, Jens Peter

AU - Tottenborg, Sandra Sogaard

PY - 2022

Y1 - 2022

N2 - 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 >80% of the samples and were included in anal-yses. 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 a priori-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 (-8%; 95% CI: -16%, -1%), total sperm count (-10%; 95% CI: -17%, -2%), 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 mater-nal 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. https://doi.org/10.1289/EHP10285

AB - 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 >80% of the samples and were included in anal-yses. 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 a priori-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 (-8%; 95% CI: -16%, -1%), total sperm count (-10%; 95% CI: -17%, -2%), 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 mater-nal 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. https://doi.org/10.1289/EHP10285

KW - PERFLUORINATED ALKYL ACIDS

KW - NATIONAL BIRTH COHORT

KW - HUMAN SEMEN QUALITY

KW - PERFLUOROALKYL SUBSTANCES

KW - FETAL ORGANS

KW - CORD BLOOD

KW - IN-UTERO

KW - SERUM

KW - PERFLUOROOCTANESULFONATE

KW - FERTILITY

U2 - 10.1289/EHP10285

DO - 10.1289/EHP10285

M3 - Journal article

C2 - 36197086

VL - 130

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

SN - 0091-6765

IS - 10

M1 - 107001

ER -