{"paper_id":"bc9dfc20-205c-4af9-a210-10c0ef93903f","body_text":"Abstract\nPurpose\nEndocrine disrupting compounds (EDCs) have been shown to affect multiple biologic processes especially steroid-hormone processes. We sought to determine differences in DNA methylation exists between women with and without endometriosis following exposure to polybrominated biphenyl (PBB).\nMethods\nCross-sectional study of 305 females in the Michigan PBB Registry. DNA was extracted, and DNA methylation was interrogated using the MethylationEPIC BeadChip (Illumina, San Diego, California). Demographic data was analyzed using Chi-squared and T tests. Linear regressions were performed for each cytosine-guanine dinucleotide (CpG) site, modeling the logit transformation of the β value as a linear function of the presence of endometriosis. Sensitivity analyses were conducted controlling for estradiol levels and menopausal status. Replication study performed evaluating for any association between CpGs reported in the literature and our findings.\nResults\nIn total, 39,877 CpGs nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity, although none remained significant after correction for multiple comparisons (FDR < 0.05). Pathway analysis of these CpGs showed enrichment in 68 biologic pathways involved in various endocrine, immunologic, oncologic, and cell regulation processes as well as embryologic reproductive tract development and function (FoxO, Wnt, and Hedgehog signaling). We identified 42,261 CpG sites in the literature reported to be associated with endometriosis; 2012 of these CpG sites were also significant in our cohort.\nConclusion\nWe found 39,877 CpG sites that nominally associated with endometriosis (p < 0.05) after adjusting for age and cellular heterogeneity; however, none remained significant after correction for multiple comparisons (FDR < 0.05).\nSimilar content being viewed by others\nReferences\nGiudice LC. Clinical practice Endometriosis. N Engl J Med. 2010;362(25):2389–98.\nGoldstein DP, deCholnoky C, Emans SJ, Leventhal JM. Laparoscopy in the diagnosis and management of pelvic pain in adolescents. J Reprod Med. 1980;24(6):251–6.\nEskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin N Am. 1997;24(2):235–58.\nMissmer SA, Hankinson SE, Spiegelman D, Barbieri RL, Marshall LM, Hunter DJ. Incidence of laparoscopically confirmed endometriosis by demographic, anthropometric, and lifestyle factors. 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Int J Epidemiol. 2018;47:917–27.\nFunding\nThis project was financed by the following grants: National Institutes of Environmental Health Sciences (5RO1ES024790, 5RO1ES025775, R24ES028528, 5P30ES019776) and the National Institute of General Medicine Sciences (T32GM008490).\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nConflict of interest\nThe authors declare that they have no conflict of interest.\nAdditional information\nPublisher’s note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nElectronic supplementary material\nESM 1 (download XLSX )\n(XLSX 66099 kb)\nESM 2 (download XLSX )\n(XLSX 29 kb)\nESM 3 (download XLSX )\n(XLSX 75385 kb)\nESM 4 (download XLSX )\n(XLSX 71300 kb)\nESM 5 (download XLSX )\n(XLSX 72521 kb)\nESM 6 (download XLSX )\n(XLSX 3874 kb)\nRights and permissions\nAbout this article\nCite this article\nGerkowicz, S.A., Curtis, S.W., Knight, A.K. et al. Endometriosis, endocrine disrupters, and epigenetics: an investigation into the complex interplay in women with polybrominated biphenyl exposure and endometriosis. J Assist Reprod Genet 37, 427–436 (2020). https://doi.org/10.1007/s10815-020-01695-9\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s10815-020-01695-9","source_license":"CC0","license_restricted":false}