PMID- 35988832 OWN - NLM STAT- MEDLINE DCOM- 20220914 LR - 20230415 IS - 1096-0953 (Electronic) IS - 0013-9351 (Linking) VI - 214 IP - Pt 4 DP - 2022 Nov TI - Urinary phthalate metabolites and their mixtures are associated with advanced sperm epigenetic aging in a general population. PG - 114115 LID - S0013-9351(22)01442-6 [pii] LID - 10.1016/j.envres.2022.114115 [doi] AB - INTRODUCTION: We have recently shown that sperm epigenetic age (SEA), a surrogate measure of biological aging in sperm, is associated with couples' time-to-pregnancy (TTP). Advanced SEA was also observed among smokers, suggesting its susceptibility to environmental exposures. Therefore, we assessed the association between urinary phthalate metabolites and SEA in male partners of couples planning to conceive among the general population. METHOD: The Longitudinal Investigation of Fertility and the Environment (LIFE) Study was a prospective multi-site and general population cohort study of couples who were interested in becoming pregnant. Among male partners (n = 333), eleven urinary phthalate metabolites were measured and SEA was previously developed using Super Learner ensemble algorithm. Multivariable linear regression was used to evaluate associations of SEA with individual metabolites. Bayesian kernel machine regression (BKMR), quantile g-computation (qgcomp) and weighted quantile sum (WQS) models were used for mixture analyses. Covariates included were BMI, cotinine, race and urinary creatinine. RESULT: In the single metabolite multivariate analyses, nine (82%) phthalate metabolites displayed positive trends with SEA (range: 0.05-0.47 years). Of these metabolites, advanced SEA was significantly associated with interquartile range increases in exposure of three phthalates [MEHHP (beta = 0.23, 95% CI: 0.03, 0.43, p = 0.03), MMP (beta = 0.24, 95% CI: 0.01, 0.47, p = 0.04), and MiBP (beta = 0.47, 95% CI: 0.14, 0.81, p = 0.01)]. Additionally, in BKMR and qgcomp (p = 0.06), but not WQS models, phthalate mixtures showed an overall positive trend with SEA, with MiBP, MMP and MBzP as major drivers of the mixture effects. CONCLUSION: This is the first study that combined single exposure and mixture models to associate male phthalate exposures with advanced epigenetic aging of sperm in men planning to conceive among the general population. Our findings suggest that phthalate exposure may contribute to the acceleration of biological aging of sperm. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Oluwayiose, Oladele A AU - Oluwayiose OA AD - C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA. FAU - Houle, Emily AU - Houle E AD - C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA. FAU - Wu, Haotian AU - Wu H AD - Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, 722 W 168th St, New York, NY, 10032, USA. FAU - Whitcomb, Brian W AU - Whitcomb BW AD - Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, 715 North Pleasant Street, Amherst, MA, USA. FAU - Mumford, Sunni L AU - Mumford SL AD - Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. FAU - Schisterman, Enrique F AU - Schisterman EF AD - Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. FAU - Suvorov, Alexander AU - Suvorov A AD - Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts Amherst, 686 North Pleasant Street, Amherst, MA, USA. FAU - Balzer, Laura B AU - Balzer LB AD - Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, 715 North Pleasant Street, Amherst, MA, USA. FAU - Pilsner, J Richard AU - Pilsner JR AD - C.S. Mott Center for Human Growth and Development, Department of Obstetrics and Gynecology, School of Medicine, Wayne State University, Detroit, MI, 48201, USA; Institute of Environmental Health Sciences, Wayne State University, Detroit, MI, 48201, USA. Electronic address: rpilsner@wayne.edu. LA - eng GR - R01 ES028298/ES/NIEHS NIH HHS/United States GR - P30 ES020957/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural DEP - 20220819 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 RN - 0 (Environmental Pollutants) RN - 0 (Phthalic Acids) RN - 6O7F7IX66E (phthalic acid) SB - IM MH - Aging MH - Bayes Theorem MH - Cohort Studies MH - Environmental Exposure MH - *Environmental Pollutants/toxicity/urine MH - Epigenesis, Genetic MH - Female MH - Humans MH - Male MH - *Phthalic Acids/urine MH - Pregnancy MH - Prospective Studies MH - Semen MH - Spermatozoa OTO - NOTNLM OT - Aging OT - DNA methylation OT - Mixtures OT - Phthalate metabolites OT - Sperm epigenetic clock COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/08/22 06:00 MHDA- 2022/09/15 06:00 CRDT- 2022/08/21 19:34 PHST- 2022/05/03 00:00 [received] PHST- 2022/07/22 00:00 [revised] PHST- 2022/08/12 00:00 [accepted] PHST- 2022/08/22 06:00 [pubmed] PHST- 2022/09/15 06:00 [medline] PHST- 2022/08/21 19:34 [entrez] AID - S0013-9351(22)01442-6 [pii] AID - 10.1016/j.envres.2022.114115 [doi] PST - ppublish SO - Environ Res. 2022 Nov;214(Pt 4):114115. doi: 10.1016/j.envres.2022.114115. Epub 2022 Aug 19.