PMID- 34649050
OWN - NLM
STAT- MEDLINE
DCOM- 20220107
LR  - 20220107
IS  - 1873-6750 (Electronic)
IS  - 0160-4120 (Linking)
VI  - 158
DP  - 2022 Jan
TI  - Associations between persistent organic pollutants and endometriosis: A 
      multiblock approach integrating metabolic and cytokine profiling.
PG  - 106926
LID - S0160-4120(21)00551-1 [pii]
LID - 10.1016/j.envint.2021.106926 [doi]
AB  - Humans are exposed daily to complex mixtures of chemical pollutants through their 
      environment and diet, some of which have the potential to disrupt the bodies' 
      natural endocrine functions and contribute to reproductive diseases like 
      endometriosis. Increasing epidemiological and experimental evidence supports the 
      association between endometriosis and certain persistent organic pollutants 
      (POPs) like dioxins; however, little is known about the underlying linking 
      mechanisms. The main objective of this study is to proof the methodological 
      applicability and discovery potential of integrating ultra-trace mass 
      spectrometry (MS) profiling of POP biomarkers and endogenous biomarker profiling 
      (MS metabolomics and cytokines) in a case-control study for the etiological 
      research of endometriosis. The approach is applied in a pilot clinical-based 
      study conducted in France where women with and without surgically confirmed 
      endometriosis were recruited. Serum samples were analysed with high-resolution MS 
      for about 30 polychlorinated biphenyls (PCBs), organochlorinated pesticides and 
      perfluoroalkyl substances (PFAS). About 600 serum metabolites and lipids were 
      identified with targeted metabolomics using tandem MS with the Biocrates MxP(R) 
      Quant 500 Kit. A panel of 4 pro-inflammatory cytokines were analysed using 
      ELISA-based 4-PLEX analyser. Statistical analysis included a battery of variable 
      selection approaches, multivariate logistic regression for single-chemical 
      associations, Bayesian kernel machine regressions (BKMR) to identify mixture 
      effects of POPs and a multiblock approach to identify shared biomarker signatures 
      among high risk clusters. The results showed the positive associations between 
      some POPs and endometriosis risk, including the pesticide trans-nonachlor Odds 
      Ratio (95% Confidence Interval) 3.38 (2.06-5.98), p < 0.0001 and PCB 114 OR (95% 
      CI) 1.83 (1.17-2.93), p = 0.009. The BKMR approach showed a tendency of a 
      positive cumulative effect of the mixture, however trans-nonachlor exhibited 
      significant associations within the mixture and interacted with other PCBs, 
      strengthening the effects at highest concentrations. Finally, the multiblock 
      analysis, relating the various blocks of data, revealed a latent cluster of women 
      with higher risk of endometrioma presenting higher concentrations of 
      trans-nonachlor, PCB 114 and dioxin-like toxic equivalents from PCBs, together 
      with an increased inflammatory profile (i.e. elevated interleukin-8 and monocyte 
      chemoattractant protein-1). It was also highlighted a specific metabolic pattern 
      characterized by dysregulation of bile acid homeostasis and lipase activity. 
      Further research will be required with larger sample size to confirm these 
      findings and gain insight on the underlying mechanisms between POPs and 
      endometriosis.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Matta, Komodo
AU  - Matta K
AD  - LABERCA, Oniris, INRAE, 44307 Nantes, France.
FAU - Lefebvre, Tiphaine
AU  - Lefebvre T
AD  - LABERCA, Oniris, INRAE, 44307 Nantes, France; Faculty of Medicine, University of 
      Nantes, Nantes, France; Department of Biology and Reproductive Medicine, 
      University Hospital of Nantes, Nantes, France.
FAU - Vigneau, Evelyne
AU  - Vigneau E
AD  - StatSC, ONIRIS, INRAE, Nantes, France.
FAU - Cariou, Veronique
AU  - Cariou V
AD  - StatSC, ONIRIS, INRAE, Nantes, France.
FAU - Marchand, Philippe
AU  - Marchand P
AD  - LABERCA, Oniris, INRAE, 44307 Nantes, France.
FAU - Guitton, Yann
AU  - Guitton Y
AD  - LABERCA, Oniris, INRAE, 44307 Nantes, France.
FAU - Royer, Anne-Lise
AU  - Royer AL
AD  - LABERCA, Oniris, INRAE, 44307 Nantes, France.
FAU - Ploteau, Stephane
AU  - Ploteau S
AD  - Faculty of Medicine, University of Nantes, Nantes, France; Service de 
      Gynecologie-obstetrique, CIC FEA, Hopital Mere Enfant, CHU Hotel Dieu, Nantes, 
      France.
FAU - Le Bizec, Bruno
AU  - Le Bizec B
AD  - LABERCA, Oniris, INRAE, 44307 Nantes, France.
FAU - Antignac, Jean-Philippe
AU  - Antignac JP
AD  - LABERCA, Oniris, INRAE, 44307 Nantes, France.
FAU - Cano-Sancho, German
AU  - Cano-Sancho G
AD  - LABERCA, Oniris, INRAE, 44307 Nantes, France. Electronic address: 
      german.cano-sancho@oniris-nantes.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211011
PL  - Netherlands
TA  - Environ Int
JT  - Environment international
JID - 7807270
RN  - 0 (Cytokines)
RN  - 0 (Environmental Pollutants)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
SB  - IM
MH  - Bayes Theorem
MH  - Case-Control Studies
MH  - Cytokines
MH  - *Endometriosis/chemically induced
MH  - *Environmental Pollutants/analysis/toxicity
MH  - Female
MH  - Humans
MH  - Persistent Organic Pollutants
MH  - *Polychlorinated Biphenyls
OTO - NOTNLM
OT  - Cytokine
OT  - Endocrine disrupting chemicals
OT  - Endometriosis
OT  - Metabolomic
OT  - Multipollutant
OT  - Persistent organic pollutants
EDAT- 2021/10/15 06:00
MHDA- 2022/01/08 06:00
CRDT- 2021/10/14 20:18
PHST- 2021/06/14 00:00 [received]
PHST- 2021/09/09 00:00 [revised]
PHST- 2021/10/06 00:00 [accepted]
PHST- 2021/10/15 06:00 [pubmed]
PHST- 2022/01/08 06:00 [medline]
PHST- 2021/10/14 20:18 [entrez]
AID - S0160-4120(21)00551-1 [pii]
AID - 10.1016/j.envint.2021.106926 [doi]
PST - ppublish
SO  - Environ Int. 2022 Jan;158:106926. doi: 10.1016/j.envint.2021.106926. Epub 2021 
      Oct 11.