PMID- 38316313 OWN - NLM STAT- MEDLINE DCOM- 20240222 LR - 20240222 IS - 1879-1026 (Electronic) IS - 0048-9697 (Linking) VI - 918 DP - 2024 Mar 25 TI - A comprehensive multiplatform metabolomic analysis reveals alterations of 2-hydroxybutyric acid among women with deep endometriosis related to the pesticide trans-nonachlor. PG - 170678 LID - S0048-9697(24)00817-9 [pii] LID - 10.1016/j.scitotenv.2024.170678 [doi] AB - BACKGROUND: Exposure to persistent organic pollutants (POPs) has been related to the risk of endometriosis however the mechanisms remain unclear. The objective of the present study was to characterize the metabolic profiles underpinning the associations between POPs and endometriosis risk. METHODOLOGY: A hospital-based case-control study was conducted in France to recruit women with and without surgically confirmed deep endometriosis. Women's serum was analyzed using gas and liquid chromatography coupled to high-resolution mass spectrometry (HRMS) to measure the levels of polychlorinated biphenyls (PCBs), organochlorinated pesticides (OCPs) and per-/polyfluoroalkyl substances (PFAS). A comprehensive metabolomic profiling was conducted using targeted HRMS and 1H nuclear magnetic resonance ((1)H NMR) to cover polar and non-polar fractions. A "meet-in-the-middle" statistical framework was applied to identify the metabolites related to endometriosis and POP levels, using multivariate linear and logistic regressions adjusting for confounding variables. RESULTS: Fourteen PCBs, six OCPs and six PFAS were widely found in almost all serum samples. The pesticide trans-nonachlor was the POP most strongly and positively associated with deep endometriosis risk, with odds ratio (95 % confidence interval) of 2.42 (1.49; 4.12), followed by PCB180 and 167. Women with endometriosis exhibited a distinctive metabolic profile, with elevated serum levels of lactate, ketone bodies and multiple amino acids and lower levels of bile acids, phosphatidylcholines (PCs), cortisol and hippuric acid. The metabolite 2-hydroxybutyrate was simultaneously associated to endometriosis risk and exposure to trans-nonachlor. CONCLUSIONS: To the best of our knowledge, this is the first comprehensive metabolome-wide association study of endometriosis, integrating ultra-trace profiling of POPs. The results confirmed a metabolic alteration among women with deep endometriosis that could be also associated to the exposure to POPs. Further observational and experimental studies will be required to delineate the causal ordering of those associations and gain insight on the underlying mechanisms. CI - Copyright (c) 2024 Elsevier B.V. All rights reserved. FAU - Lefebvre, Tiphaine AU - Lefebvre T AD - Oniris, INRAE, LABERCA, Nantes, France; CHU Nantes, Nantes Universite, Service de Medecine et Biologie de la Reproduction, Gynecologie medicale, 38 bd Jean Monnet, Nantes, France; Faculty of Medicine, Nantes Universite, France; Department of Gynecology and Obstetrics, Centre Hospitalier Departemental Vendee, 85000 la Roche sur Yon, France. FAU - Campas, Manon AU - Campas M AD - Centre for Interdisciplinary Research on Medicines (CIRM), Metabolomics Group, University of Liege, Belgium. FAU - Matta, Komodo AU - Matta K AD - Oniris, INRAE, LABERCA, Nantes, France. FAU - Ouzia, Sadia AU - Ouzia S AD - Oniris, INRAE, LABERCA, Nantes, France; MetaboHUB-MELISA, MetaboHUB-ANR-11-INBS-0010, Oniris, INRAE, LABERCA, Nantes, France. FAU - Guitton, Yann AU - Guitton Y AD - Oniris, INRAE, LABERCA, Nantes, France; MetaboHUB-MELISA, MetaboHUB-ANR-11-INBS-0010, Oniris, INRAE, LABERCA, Nantes, France. FAU - Duval, Gauthier AU - Duval G AD - Oniris, INRAE, LABERCA, Nantes, France; CHU Nantes, Nantes Universite, Service de Medecine et Biologie de la Reproduction, Gynecologie medicale, 38 bd Jean Monnet, Nantes, France. FAU - Ploteau, Stephane AU - Ploteau S AD - CHU Nantes, Nantes Universite, Service de Medecine et Biologie de la Reproduction, Gynecologie medicale, 38 bd Jean Monnet, Nantes, France; CHU Nantes, Department of Gynecology and Obstetrics, 38 bd Jean Monnet, Nantes, France. FAU - Marchand, Philippe AU - Marchand P AD - Oniris, INRAE, LABERCA, Nantes, France. FAU - Le Bizec, Bruno AU - Le Bizec B AD - Oniris, INRAE, LABERCA, Nantes, France. FAU - Freour, Thomas AU - Freour T AD - CHU Nantes, Nantes Universite, Service de Medecine et Biologie de la Reproduction, Gynecologie medicale, 38 bd Jean Monnet, Nantes, France; Department of Reproductive Medicine, Dexeus University Hospital, Barcelona, Spain. FAU - Antignac, Jean-Philippe AU - Antignac JP AD - Oniris, INRAE, LABERCA, Nantes, France. FAU - de Tullio, Pascal AU - de Tullio P AD - MetaboHUB-MELISA, MetaboHUB-ANR-11-INBS-0010, Oniris, INRAE, LABERCA, Nantes, France. FAU - Cano-Sancho, German AU - Cano-Sancho G AD - Oniris, INRAE, LABERCA, Nantes, France. Electronic address: german.canosancho@inrae.fr. LA - eng PT - Journal Article DEP - 20240203 PL - Netherlands TA - Sci Total Environ JT - The Science of the total environment JID - 0330500 RN - 3734-49-4 (nonachlor) RN - DFC2HB4I0K (Polychlorinated Biphenyls) RN - O0ADR0I4H5 (2-hydroxybutyric acid) RN - 0 (Pesticides) RN - 0 (Hydrocarbons, Chlorinated) RN - 0 (Environmental Pollutants) RN - 0 (Hydroxybutyrates) RN - 0 (Fluorocarbons) SB - IM MH - Humans MH - Female MH - *Polychlorinated Biphenyls/analysis MH - *Pesticides/analysis MH - *Endometriosis/chemically induced MH - Case-Control Studies MH - *Hydrocarbons, Chlorinated/analysis MH - *Environmental Pollutants/analysis MH - Hydroxybutyrates MH - *Fluorocarbons/analysis OTO - NOTNLM OT - Endometriosis OT - Meet-in-the-middle OT - Metabolomics OT - Persistent organic pollutants 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- 2024/02/06 00:42 MHDA- 2024/02/22 06:42 CRDT- 2024/02/05 19:24 PHST- 2023/12/12 00:00 [received] PHST- 2024/01/30 00:00 [revised] PHST- 2024/02/02 00:00 [accepted] PHST- 2024/02/22 06:42 [medline] PHST- 2024/02/06 00:42 [pubmed] PHST- 2024/02/05 19:24 [entrez] AID - S0048-9697(24)00817-9 [pii] AID - 10.1016/j.scitotenv.2024.170678 [doi] PST - ppublish SO - Sci Total Environ. 2024 Mar 25;918:170678. doi: 10.1016/j.scitotenv.2024.170678. Epub 2024 Feb 3.