AccScience Publishing / JBM / Online First / DOI: 10.14440/jbm.0148
Submit to JBM
Cite this article
9
Download
433
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
REVIEW

Genetic and stem cell insights into the pathogenesis of endometriosis: A comprehensive review

Sheena Mariam Thomas1 ,  Ramakrishnan Veerabathiran1*
Show Less
1 Human Cytogenetics and Genomics Laboratory, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam 60313, Tamil Nadu, India
JBM, e99010075 https://doi.org/10.14440/jbm.0148
Submitted: 24 January 2025 | Revised: 26 May 2025 | Accepted: 11 August 2025 | Published: 2 October 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

Background: Endometriosis represents a predominant gynecological disease that globally impacts 10% of women in their reproductive years, often leading to pelvic pain, infertility, and other complications. Objective: This review intended to impart a comprehensive understanding of the pathophysiology, inherent genetic susceptibility, and the role of stem cells in the progression of endometriosis. It explores the diagnostic challenges posed by the diverse presentation of lesions and the involvement of genetic factors, including genes related to inflammation, immune response, steroidogenesis, neo-angiogenesis, and DNA repair. In addition, the role of adult stem cells, particularly from bone marrow and the endometrium is highlighted as an important aspect of disease progression. The review also examined how environmental factors, including early menarche, heavy menstrual flow, and Müllerian anomalies, contribute to endometriosis development. The impact on fertility is discussed concerning pelvic anatomical distortions, which affect egg release, sperm motility, and embryo transit. Furthermore, the review addressed complications, such as chronic pelvic pain, dysmenorrhea, dyspareunia, and potential obstetric issues, including an increased risk of certain cancers. Finally, it emphasized the need for improved diagnostic techniques and targeted therapies, focusing on early detection, innovative treatments, and fertility preservation. Conclusion: Advancements in genomic and molecular research are crucial to understanding the genetic basis of endometriosis and ultimately enhance the quality of life for those affected.

Keywords
Endometriosis
Pathophysiology
Genetic basis
Stem cells
Infertility
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
References
[1]
  1. Smolarz B, Szyłło K, Romanowicz H. Endometriosis: Epidemiology, classification, pathogenesis, treatment and genetics (review of literature). Int J Mol Sci. 2021;22(19):10554. doi: 10.3390/ijms221910554

 

  1. Rout D, Sinha A, Palo SK, Kanungo S, Pati S. Prevalence and determinants of hysterectomy in India. Sci Rep. 2023;13(1):14569. doi: 10.1038/s41598-023-41863-2

 

  1. Chauhan S, More A, Chauhan V, Kathane A. Endometriosis: A review of clinical diagnosis, treatment, and pathogenesis. Cureus. 2022;14(9):e28864. doi: 10.7759/cureus.28864

 

  1. Greene AD, Lang SA, Kendziorski JA, Sroga-Rios JM, Herzog TJ, Burns KA. Endometriosis: Where are we and where are we going? Reproduction. 2016;152(3):R63-R78. doi: 10.1530/REP-16-0052

 

  1. Mehedintu C, Plotogea MN, Ionescu S, Antonovici M. Endometriosis still a challenge. J Med Life. 2014;7(3):349-357.

 

  1. Malvezzi H, Marengo EB, Podgaec S, Piccinato CA. Endometriosis: Current challenges in modeling a multifactorial disease of unknown etiology. J Transl Med. 2020;18(1):311. doi: 10.1186/s12967-020-02471-0

 

  1. Imperiale L, Nisolle M, Noël JC, Fastrez M. Three types of endometriosis: Pathogenesis, diagnosis and treatment. State of the art. J Clin Med. 2023;12(3):994. doi: 10.3390/jcm12030994

 

  1. Johnson NP, Hummelshoj L, World Endometriosis Society Montpellier Consortium. Consensus on current management of endometriosis. Hum Reprod. 2013;28(6):1552-1568. doi: 10.1093/humrep/det050

 

  1. Kobayashi H, Higashiura Y, Shigetomi H, Kajihara H. Pathogenesis of endometriosis: The role of initial infection and subsequent sterile inflammation (Review). Mol Med Rep. 2014;9(1):9-15. doi: 10.3892/mmr.2013.1755

 

  1. Sourial S, Tempest N, Hapangama DK. Theories on the pathogenesis of endometriosis. Int J Reprod Med. 2014;2014:179515. doi: 10.1155/2014/179515

 

  1. Koninckx PR, Ussia A, Adamyan L, Wattiez A, Donnez J. Deep endometriosis: Definition, diagnosis, and treatment. Fertil Steril. 2012;98(3):564-571. doi: 10.1016/j.fertnstert.2012.07.1061

 

  1. Wahl KJ, Orr NL, Lisonek M, et al. Deep dyspareunia, superficial dyspareunia, and infertility concerns among women with endometriosis: A cross-sectional study. Sex Med. 2020;8(2):274-281. doi: 10.1016/j.esxm.2020.01.002

 

  1. Saunders PTK, Horne AW. Endometriosis: Etiology, pathobiology, and therapeutic prospects. Cell. 2021;184(11):2807-2824. doi: 10.1016/j.cell.2021.04.041

 

  1. van der Linden PJ. Theories on the pathogenesis of endometriosis. Hum Reprod. 1996;11 Suppl 3:53-65. doi: 10.1093/humrep/11.suppl_3.53

 

  1. Bulun SE. Endometriosis caused by retrograde menstruation: Now demonstrated by DNA evidence. Fertil Steril. 2022;118(3):535-536. doi: 10.1016/j.fertnstert.2022.07.012

 

  1. Irungu S, Mavrelos D, Worthington J, Blyuss O, Saridogan E, Timms JF. Discovery of non-invasive biomarkers for the diagnosis of endometriosis. Clin Proteomics. 2019;16:14. doi: 10.1186/s12014-019-9235-3

 

  1. Carpinello OJ, Sundheimer LW, Alford CE, Taylor RN, DeCherney AH. Endometriosis. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext. South Dartmouth, MA: MDText.com, Inc.; 2017.

 

  1. McLeod BS, Retzloff MG. Epidemiology of endometriosis: An assessment of risk factors. Clin Obstet Gynecol. 2010;53(2):389-396. doi: 10.1097/GRF.0b013e3181db7bde

 

  1. Chantalat E, Valera MC, Vaysse C, et al. Estrogen receptors and endometriosis. Int J Mol Sci. 2020;21(8):2815. doi: 10.3390/ijms21082815

 

  1. Vassilopoulou L, Matalliotakis M, Zervou MI, et al. Defining the genetic profile of endometriosis. Exp Ther Med. 2019;17(5):3267-3281. doi: 10.3892/etm.2019.7346

 

  1. Vitonis AF, Baer HJ, Hankinson SE, Laufer MR, Missmer SA. A prospective study of body size during childhood and early adulthood and the incidence of endometriosis. Hum Reprod. 2010;25(5):1325-1334. doi: 10.1093/humrep/deq039

 

  1. de Angelis C, Nardone A, Garifalos F, et al. Smoke, alcohol and drug addiction and female fertility. Reprod Biol Endocrinol. 2020;18(1):21. doi: 10.1186/s12958-020-0567-7

 

  1. Parazzini F, Chiaffarino F, Surace M, et al. Selected food intake and risk of endometriosis. Hum Reprod. 2004;19(8):1755-1759. doi: 10.1093/humrep/deh395

 

  1. Lee GH, Kim SH, Choi YM, Suh CS, Kim JG, Moon SY. Estrogen receptor beta gene +1730 G/A polymorphism in women with endometriosis. Fertil Steril. 2007;88(4):785-788. doi: 10.1016/j.fertnstert.2006.12.032

 

  1. Angioni S, D’Alterio MN, Coiana A, Anni F, Gessa S, Deiana D. Genetic characterization of endometriosis patients: Review of the literature and a prospective cohort study on a mediterranean population. Int J Mol Sci. 2020;21(5):1765. doi: 10.3390/ijms21051765

 

  1. Hassani M, Saliminejad K, Heidarizadeh M, Kamali K, Memariani T, Khorram Khorshid HR. Association study of Glutathione S-Transferase polymorphisms and risk of endometriosis in an Iranian population. Int J Reprod Biomed. 2016;14(4):241-246.

 

  1. Cardoso JV, Perini JA, Machado DE, Pinto R, Medeiros R. Systematic review of genome-wide association studies on susceptibility to endometriosis. Eur J Obstet Gynecol Reprod Biol. 2020;255:74-82. doi: 10.1016/j.ejogrb.2020.10.017

 

  1. Deiana D, Gessa S, Anardu M, et al. Genetics of endometriosis: A comprehensive review. Gynecol Endocrinol. 2019;35(7):553-558. doi: 10.1080/09513590.2019.1588244

 

  1. Prochazkova M, Chavez MG, Prochazka J, Felfy H, Mushegyan V, Klein OD. Embryonic versus adult stem cells. In: Stem Cell Biology and Tissue Engineering in Dental Sciences. United States: Academic Press.; 2015. p. 249-262. doi: 10.1016/B978-0-12-397157-9.00020-5

 

  1. Dhesi AS, Morelli SS. Endometriosis: A role for stem cells. Womens Health (Lond). 2015;11(1):35-49. doi: 10.2217/whe.14.57

 

  1. Gargett CE, Chan RW, Schwab KE. Hormone and growth factor signaling in endometrial renewal: Role of stem/progenitor cells. Mol Cell Endocrinol. 2008;288(1-2):22-29. doi: 10.1016/j.mce.2008.02.026

 

  1. Gargett CE, Masuda H. Adult stem cells in the endometrium. Mol Hum Reprod. 2010;16(11):818-834. doi: 10.1093/molehr/gaq061

 

  1. Adamyan L, Pivazyan L, Krylova E, Tarlakyan V, Murvatova K. Iron metabolism markers in peritoneal fluid of patients with endometriosis: Systematic review and meta-analysis. J Endometr Uterine Disord. 2024;5:100061. doi: 10.1016/j.jeud.2024.100061

 

  1. Adamyan L, Pivazyan L, Zarova E, et al. Metabolomic biomarkers of endometriosis: A systematic review. J Endometr Uterine Disord. 2024;7:100077. doi: 10.1016/j.jeud.2024.100077

 

  1. Becker CM, Beaudry P, Funakoshi T, et al. Circulating endothelial progenitor cells are up-regulated in a mouse model of endometriosis. Am J Pathol. 2011;178(4):1782-1791. doi: 10.1016/j.ajpath.2010.12.037

 

  1. Ferrer AI, Einstein E, Morelli SS. Bone Marrow-derived cells in endometrial cancer pathogenesis: Insights from breast cancer. Cells. 2022;11(4):714. doi: 10.3390/cells11040714

 

  1. Wang Y, Nicholes K, Shih IM. The origin and pathogenesis of endometriosis. Annu Rev Pathol. 2020;15:71-95. doi: 10.1146/annurev-pathmechdis-012419-032654

 

  1. Borisova AV, Konnon SRD, Tosto V, Gerli S, Radzinsky VE. Obstetrical complications and outcome in patients with endometriosis. J Matern Fetal Neonatal Med. 2022;35(14):2663-2677. doi: 10.1080/14767058.2020.1793326

 

  1. Macer ML, Taylor HS. Endometriosis and infertility: A review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012;39(4):535-549. doi: 10.1016/j.ogc.2012.10.002

 

  1. Máté G, Bernstein LR, Török AL. Endometriosis is a cause of infertility. Does reactive oxygen damage to gametes and embryos play a key role in the pathogenesis of infertility caused by endometriosis? Front Endocrinol (Lausanne). 2018;9:725. doi: 10.3389/fendo.2018.00725

 

  1. Bonavina G, Taylor HS. Endometriosis-associated infertility: From pathophysiology to tailored treatment. Front Endocrinol (Lausanne). 2022;13:1020827. doi: 10.3389/fendo.2022.1020827

 

  1. Gaetje R, Holtrich U, Karn T, et al. Characterization of WNT7A expression in human endometrium and endometriotic lesions. Fertil Steril. 2007;88(6):1534-1540. doi: 10.1016/j.fertnstert.2007.01.128

 

  1. Lin YH, Chen YH, Chang HY, Au HK, Tzeng CR, Huang YH. Chronic niche inflammation in endometriosis-associated infertility: Current understanding and future therapeutic strategies. Int J Mol Sci. 2018;19(8):2385. doi: 10.3390/ijms19082385

 

  1. Anglesio MS, Yong PJ. Endometriosis-associated ovarian cancers. Clin Obstet Gynecol. 2017;60(4):711-727. doi: 10.1097/GRF.0000000000000320

 

  1. Samartzis EP, Labidi-Galy SI, Moschetta M, et al. Endometriosis-associated ovarian carcinomas: Insights into pathogenesis, diagnostics, and therapeutic targets-a narrative review. Ann Transl Med. 2020;8(24):1712. doi: 10.21037/atm-20-3022a

 

  1. Worley MJ, Welch WR, Berkowitz RS, Ng SW. Endometriosis-associated ovarian cancer: A review of pathogenesis. Int J Mol Sci. 2013;14(3):5367-5379. doi: 10.3390/ijms14035367

 

  1. Tian Z, Chang XH, Zhao Y, Zhu HL. Current biomarkers for the detection of endometriosis. Chin Med J (Engl). 2020;133(19):2346-2352. doi: 10.1097/CM9.0000000000001063

 

  1. Szubert M, Rycerz A, Wilczyński JR. How to improve non-invasive diagnosis of endometriosis with advanced statistical methods. Medicina (Kaunas). 2023;59(3):499. doi: 10.3390/medicina59030499

 

  1. Connal S, Cameron JM, Sala A, et al. Liquid biopsies: The future of cancer early detection. J Transl Med. 2023;21(1):118. doi: 10.1186/s12967-023-03960-8

 

  1. Hansen KA, Eyster KM. Genetics and genomics of endometriosis. Clin Obstet Gynecol. 2010;53(2):403-412. doi: 10.1097/GRF.0b013e3181db7ca1
Share
Back to top
Journal of Biological Methods, Electronic ISSN: 2326-9901 Print ISSN: TBA, Published by POL Scientific
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept