Using mixture and exposome methods to assess the associations and interactions of chemical biomarkers with semen parameters

Background: Although epidemiologic studies have found associations between several chemical biomarkers and semen parameters, only a few studies have evaluated their combined effects and interactions. Methods: We included 420 men aged 18–55 years who participated in the Environment and Reproductive H...

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Main Authors: Maximilien Génard-Walton, Charline Warembourg, Paige L. Williams, Irene Souter, Jennifer B. Ford, Jorge E. Chavarro, Russ Hauser, Lidia Mínguez-Alarcón
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Environment International
Online Access:http://www.sciencedirect.com/science/article/pii/S0160412025003198
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author Maximilien Génard-Walton
Charline Warembourg
Paige L. Williams
Irene Souter
Jennifer B. Ford
Jorge E. Chavarro
Russ Hauser
Lidia Mínguez-Alarcón
author_facet Maximilien Génard-Walton
Charline Warembourg
Paige L. Williams
Irene Souter
Jennifer B. Ford
Jorge E. Chavarro
Russ Hauser
Lidia Mínguez-Alarcón
author_sort Maximilien Génard-Walton
collection DOAJ
description Background: Although epidemiologic studies have found associations between several chemical biomarkers and semen parameters, only a few studies have evaluated their combined effects and interactions. Methods: We included 420 men aged 18–55 years who participated in the Environment and Reproductive Health (EARTH) study between 2005 and 2019 at the Massachusetts General Hospital Fertility Center. Four mixture/exposome models, including exposome-wide association studies (ExWAS), Deletion/Substitution/Addition algorithm (DSA), Bayesian Kernel Machine Regression (BKMR), and the non-linear interaction model (NLinteraction), were used to evaluate associations between 24 chemical biomarkers (urinary bisphenol A, four parabens, triclosan, 17 phthalate metabolites, and hair mercury [Hg]) and semen parameters (sperm count, concentration, morphology, motility, and semen volume). Results: Overall, Hg was positively, and triclosan was negatively significantly associated with all semen outcomes except semen volume across multiple models. In BKMR, when increasing the mixture from the 10th to 90th percentile, the chemical mixture was negatively associated with percent normal sperm morphology (−1.42 %, 95 % Credibility Interval [CRI] −12.36; 9.52), motility (−0.10 %, 95 % CRI −1.78; 1.58), and volume (−0.26 mL, 95 % CRI −0.79; 0.28), and positively associated with sperm count (0.21 mill, 95 % CRI −0.23; 0.65) and concentration (0.33 mill/mL, 95 % CRI −0.14; 0.80). We detected one interaction between urinary triclosan and butylparaben in relation to normal sperm morphology using NLinteraction. Conclusion: Among 24 biomarkers tested, Hg and triclosan showed consistent associations with semen parameters while other biomarkers were less consistent depending on the model used. Similar research studies should be encouraged to use multiple models to incorporate interaction assessment and assess the robustness of results.
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spelling doaj-art-5e6bea91f274461fb739316dcf85367b2025-08-20T03:30:49ZengElsevierEnvironment International0160-41202025-07-0120110956810.1016/j.envint.2025.109568Using mixture and exposome methods to assess the associations and interactions of chemical biomarkers with semen parametersMaximilien Génard-Walton0Charline Warembourg1Paige L. Williams2Irene Souter3Jennifer B. Ford4Jorge E. Chavarro5Russ Hauser6Lidia Mínguez-Alarcón7Université Grenoble Alpes, Inserm, CNRS, IAB, Site Santé, Allée des Alpes, 38700 La Tronche, France; Corresponding author at: Institut pour l’Avancée des Biosciences, Site Santé, Allée des Alpes, 38700 La Tronche, France.Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, FranceDepartments of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, USAVincent Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USADepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, USADepartments of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Harvard Medical School & Brigham and Women’s Hospital, USADepartments of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, USA; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, USA; Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, USADepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Harvard Medical School & Brigham and Women’s Hospital, USABackground: Although epidemiologic studies have found associations between several chemical biomarkers and semen parameters, only a few studies have evaluated their combined effects and interactions. Methods: We included 420 men aged 18–55 years who participated in the Environment and Reproductive Health (EARTH) study between 2005 and 2019 at the Massachusetts General Hospital Fertility Center. Four mixture/exposome models, including exposome-wide association studies (ExWAS), Deletion/Substitution/Addition algorithm (DSA), Bayesian Kernel Machine Regression (BKMR), and the non-linear interaction model (NLinteraction), were used to evaluate associations between 24 chemical biomarkers (urinary bisphenol A, four parabens, triclosan, 17 phthalate metabolites, and hair mercury [Hg]) and semen parameters (sperm count, concentration, morphology, motility, and semen volume). Results: Overall, Hg was positively, and triclosan was negatively significantly associated with all semen outcomes except semen volume across multiple models. In BKMR, when increasing the mixture from the 10th to 90th percentile, the chemical mixture was negatively associated with percent normal sperm morphology (−1.42 %, 95 % Credibility Interval [CRI] −12.36; 9.52), motility (−0.10 %, 95 % CRI −1.78; 1.58), and volume (−0.26 mL, 95 % CRI −0.79; 0.28), and positively associated with sperm count (0.21 mill, 95 % CRI −0.23; 0.65) and concentration (0.33 mill/mL, 95 % CRI −0.14; 0.80). We detected one interaction between urinary triclosan and butylparaben in relation to normal sperm morphology using NLinteraction. Conclusion: Among 24 biomarkers tested, Hg and triclosan showed consistent associations with semen parameters while other biomarkers were less consistent depending on the model used. Similar research studies should be encouraged to use multiple models to incorporate interaction assessment and assess the robustness of results.http://www.sciencedirect.com/science/article/pii/S0160412025003198
spellingShingle Maximilien Génard-Walton
Charline Warembourg
Paige L. Williams
Irene Souter
Jennifer B. Ford
Jorge E. Chavarro
Russ Hauser
Lidia Mínguez-Alarcón
Using mixture and exposome methods to assess the associations and interactions of chemical biomarkers with semen parameters
Environment International
title Using mixture and exposome methods to assess the associations and interactions of chemical biomarkers with semen parameters
title_full Using mixture and exposome methods to assess the associations and interactions of chemical biomarkers with semen parameters
title_fullStr Using mixture and exposome methods to assess the associations and interactions of chemical biomarkers with semen parameters
title_full_unstemmed Using mixture and exposome methods to assess the associations and interactions of chemical biomarkers with semen parameters
title_short Using mixture and exposome methods to assess the associations and interactions of chemical biomarkers with semen parameters
title_sort using mixture and exposome methods to assess the associations and interactions of chemical biomarkers with semen parameters
url http://www.sciencedirect.com/science/article/pii/S0160412025003198
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