Exploring the Effects of Endocrine-Disrupting Chemicals and miRNA Expression in the Pathogenesis of Endometriosis by Unveiling the Pathways: a Systematic Review

Endometriosis, characterized by endometrial-like mucosal tissue outside the uterine cavity, is a reproductive disorder afflicting about 10% of women within the reproductive age. The pathogenesis of endometriosis has been attributed to factors like genetics, environmental particles, and hormones. A comprehensive review of studies from July 2010 to July 2023 across multiple databases was done to aid in a better understanding of the same. The investigation focused on studies delineating the correlation between endocrine disruptors, microRNAs, and endometriosis. To optimize the search scope, keywords and subject headings were used as search terms. Then, two authors rigorously assessed studies using criteria, selecting 27 studies from various databases. Notably, dioxins, organochlorine pesticides, and polychlorinated biphenyls exhibited a solid connection for endometriosis, while bisphenol A and phthalates yielded conflicting results. The heightened presence of bisphenol A, polychlorinated biphenyls, and phthalates was linked to altered gene expression, including genes like AKR1B10, AKR1C3, and FAM49B. MicroRNAs like miRNA-31, miRNA-144, and miRNA-145 emerged as vital factors in the onset of endometriosis and progression. Furthermore, elevated expression of miR-1304-3p, miR-544, and miR-3684 and reduced expression of miR-3935 and miR-4427 exert substantial influence on signaling pathways like NF-κB, MAPK, and Wnt/β-catenin. Currently, literature shows an independent link between endocrine disruptor exposure and endometriosis and between microRNA dysregulation and endometriosis. However, research lacks the combination of all three factors. The review delves into the effects of endocrine disruptors and microRNAs on the pathogenesis of endometriosis to improve our understanding of the disorder and in finding therapies. Graphical Abstract Similar content being viewed by others Data Availability All data supporting the findings of this study are available within the paper and its Supplementary Information. Code Availability NA. Abbreviations - EDC: - Endocrine-disrupting chemicals - BPA: - Bisphenol A - PCB: - Polychlorinated biphenyl - DEHP: - Di-(2-ethylhexyl)-phthalate - ROS: - Reactive oxygen species - SOD: - Superoxide dismutase - GPX: - Glutathione peroxidase - HO: - Heme oxygenase - CAT: - Catalase - miRNA: - MicroRNA - F1: - Filial 1 - OCP: - Organochlorine pesticide - PAE: - Phthalate ester - PDBE: - Polybrominated diphenyl ethers - DIE: - Deep infiltrating endometriosis - 2,3,7,8-TCDD: - 2,3,7,8-Tetrachlorodibenzo-p-dioxin - 1,2,3,7,8-PeCDD: - 1,2,3,7,8-Pentachlorodibenzo-p-dioxin - MnBP: - Mono-n-butyl phthalate - BIRC3: - Baculoviral IAP repeat containing 3 - BUB1B: - Mitotic checkpoint serine/threonine-protein kinase BUB1 beta - CDC20: - Cell division cycle protein 2 - IL-1β: - Interleukin-1 beta - TNF-α: - Tumor necrosis factor-alpha - DBP: - Dibutyl phthalate - GTP: - Guanine triphosphate - E2F: - E2 transcription factor - MMP: - Metalloproteinase - MiBP: - Mono-isobutyl phthalate - MOP: - Mono-octyl phthalate - MBP: - Mono-butyl phthalate - MCHP: - Mono-cyclohexyl phthalate - MEHP: - Mono-(ethylhexyl) phthalate - MiNP: - Mono-isononyl phthalate - MBzP: - Methylbenzylpiperazine - POP: - Persistent organic pollutants - WQS: - Weighted quantile sum - BKMR: - Bayesian kernel machine regression - OF: - Omental fat - PBDE: - Polybrominated diphenyl ether - γ-HCH: - Gamma-hexachlorocyclohexane - PF: - Peritoneal fluid - MEHHP: - Mono(2-ethyl-5-hydroxyhexyl) phthalate - MEOHP: - Mono-(2-ethyl-5-oxohexyl) phthalate - MEP: - Monoethyl phthalate - AKR: - Aldo-keto reductase - qPCR: - Quantitative polymerase chain reaction - mTOR: - Mammalian target of rapamycin - VEGF: - Vascular endothelial growth factor - NK: - Natural killer - PI3K/Akt: - Phosphoinositide-3-kinase-protein kinase B/Ak strain transforming - MAPK: - Mitogen-activated protein kinase - mRNA: - Messenger RNA - HOXA10: - Homeobox - EuE: - Ectopic endometrial - EcE: - Eutopic endometrial - IGFBP3: - Insulin-like growth factor binding protein 3 - COL8A1: - Collagen type VIII alpha 1 chain - Crk: - Protein-proto-oncogene - AFS: - American Fertility Society - NTN4: - Netrin 4 - CD14: - Cluster of differentiation 14 - NF-κB: - Nuclear factor-kappa B - M1: - Macrophage markers - IRF5: - Interferon regulatory factor 5 - SF -1: - Steroidogenic factor 1 - ECSCs: - Ectopic endometrial stroma cells - StAR: - Steroidogenic acute regulatory protein - CYP19A1: - Cytochrome P450 family 19 subfamily A member 1 - ELNE: - Neutrophil elastase - AMH: - Anti-Müllerian hormone - JAK/STAT: - Janus kinase/signal transducers and activators of transcription - YAP/TAZ: - Yes-associated protein and the transcriptional coactivator with PDZ-binding motif - Wnt: - Wingless-related integration site - FOXO: - Forkhead box O - p53: - Tumor protein - TGF-ß: - Transforming growth factor beta - ECM: - Extracellular matrix - BMP7: - Bone morphogenetic protein-7

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The collection of data has been contributed by all the students working in the laboratory and supported by the Department of Biotechnology, SRM Institute of Science and Technology. We sincerely feel grateful towards Usharani Balu, Deva Sureshbabu, S. Murali Krishnan, Sweta Thakkar, Sooriyakumar S., Sandhya Ramanan, and Uma K. Arun. Author information Authors and Affiliations Corresponding author Ethics declarations Ethical Approval All the studies quoted in this review article have studies involving human participants that were in accordance with the ethical standards of the institutional and/or national research committee. Consent to Participate NA for systematic review. Consent for Publication The authors affirm that human samples were not collected for this study. Conflict of Interest The authors declare no competing interests. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Chandrakanth, A., Firdous, S., Vasantharekha, R. et al. Exploring the Effects of Endocrine-Disrupting Chemicals and miRNA Expression in the Pathogenesis of Endometriosis by Unveiling the Pathways: a Systematic Review. Reprod. Sci. 31, 932–941 (2024). https://doi.org/10.1007/s43032-023-01412-8 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-023-01412-8