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

  • Endometriosis: Review
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Abstract

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.

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Data Availability

All data supporting the findings of this study are available within the paper and its Supplementary Information.

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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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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, 603203, India

    Akshaya Chandrakanth, Sana Firdous, Ramasamy Vasantharekha & Barathi Seetharaman

  2. P.G. & Research Department of Advanced Zoology and Biotechnology, Government College for Men, Nandanam, Chennai, Tamil Nadu, India

    Winkins Santosh

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  1. Akshaya Chandrakanth
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Correspondence to Barathi Seetharaman.

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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.

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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

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