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Journal of Assisted Reproduction and Genetics
Published in: Journal of Assisted Reproduction and Genetics 2/2020

01-02-2020 | Endometriosis | Reproductive Physiology and Disease

Endometriosis, endocrine disrupters, and epigenetics: an investigation into the complex interplay in women with polybrominated biphenyl exposure and endometriosis

Authors: Sabrina A. Gerkowicz, Sarah W. Curtis, Anna K. Knight, Dawayland O. Cobb, Jessica B. Spencer, Karen N. Conneely, Metrecia L. Terrell, Michele Marcus, Alica K. Smith

Published in: Journal of Assisted Reproduction and Genetics | Issue 2/2020

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Abstract

Purpose

Endocrine 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).

Methods

Cross-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.

Results

In 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.

Conclusion

We 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).
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Metadata
Title
Endometriosis, endocrine disrupters, and epigenetics: an investigation into the complex interplay in women with polybrominated biphenyl exposure and endometriosis
Authors
Sabrina A. Gerkowicz
Sarah W. Curtis
Anna K. Knight
Dawayland O. Cobb
Jessica B. Spencer
Karen N. Conneely
Metrecia L. Terrell
Michele Marcus
Alica K. Smith
Publication date
01-02-2020
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 2/2020
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-020-01695-9

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