Clinical review for general practice

ISSN (Print) 2713-2552
ISSN (Online) 2782-5671
  • Home
  • about
  • archives
  • contacts
left
FULLSCREEN > Archive > 2024 > Vol 5, №4 (2024) > ARID1a expression in the endometrium of women of reproductive age with abnormal uterine bleeding and obesity

ARID1a expression in the endometrium of women of reproductive age with abnormal uterine bleeding and obesity

Marina B. Khamoshina , Gulrukhsor Kh. Tolibova , Tatyana G. Tral , Yulia S. Artemenko

For citation:


  • Abstract
  • About the Author
  • References

Abstract

Objective. The aim of the study was to evaluate the expression of the proliferative marker ARID1a in endometrial biopsies of patients with abnormal uterine bleeding (AUB) and obesity and its role in the pathogenesis of endometrial dysfunction.
Materials and methods. The study included 40 endometrial samples from patients of reproductive age with AUB-E: 20 from patients with AUB-E and obesity (group 1) and 20 from patients with normal body mass index (BMI) and AUB (group 2). 10 endometrial samples were obtained from healthy women of reproductive age, taken on the 2nd-3rd day of the menstrual cycle. All patients underwent histological examination according to the standard procedure. At the second stage, an immunohistochemical study of the ARID1a proliferation marker was performed using polyclonal rabbit antibodies to Anti-ARID1a (clone EPR13501-73) in standard dilution (1:500) according to the protocol of the manufacturer 
Abcam (Great Britain). The IBM SPSS Statistics v.26 program (IBM Corporation, USA) was used for statistical data analysis. To determine statistically significant differences between quantitative parameters with a normal distribution, one-factor analysis of variance (ANOVA) was used with the calculation of a 95% confidence interval followed by the post-hoc Games-Howell test for multiple comparisons. The differences were considered significant at p<0.05.
Results. ARID1a expression was evaluated in the glandular and stromal compartments of the endometrium. In the endometrial glands, the expression of ARID1a was statistically significantly higher in the first group of obese patients compared with the normal and control groups. In the endometrial stroma, the expression of the proliferative marker was higher in the main group compared with the control group. However, when comparing between groups within the main group, statistical significance in the level of expression was not achieved.
Conclusion. The results obtained demonstrate the possible pathological effect of obesity on the structural and functional properties of the endometrium, which leads to delayed regeneration of the endometrium due to the glandular component and, consequently, to AUB-E.
Keywords: abnormal uterine bleeding, obesity, endometrial dysfunction, ARID1a.

About the Author

Marina B. Khamoshina 1 , Gulrukhsor Kh. Tolibova 2 , Tatyana G. Tral 3 , Yulia S. Artemenko 1

1 Patrice Lumumba People’s Friendship University of Russia, Moscow, Russia

2 Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia; Mechnikov North-Western State Medical University, Saint Petersburg, Russia

3 Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia

References

1. Heavy menstrual bleeding: assessment and management. London: National Institute for Health and Care Excellence (NICE), May 24, 2018.
2. Munro MG, Critchley HOD, Fraser IS; FIGO Menstrual Disorders Committee. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynaecol Obstet. 2018;143(3):393-408. DOI:10.1002/ijgo.12666
3. Аномальные маточные кровотечения. Клинические рекомендации. Минздрав России. М., 2021. Дата обращения: 12.03.2024. URL: https://cr.minzdrav.gov.ru/recomend/645_1
Abnormal uterine bleeding. Clinical recommendations Ministry of Health of the Russian Federation. Moscow, 2021. URL: https://cr. minzdrav.gov.ru/recomend/645_1. Date of application: 12.03.2024 (in Russian).
4. Dutton B, Kai J. Women’s experiences of heavy menstrual bleeding and medical treatment: a qualitative study in primary care. Br J Gen Pract. 2023;73(729):e294-e301. DOI: 10.3399/BJGP.2022.0460
5. Wang YX, Arvizu M, Rich-Edwards JW et al. Menstrual cycle regularity and length across the reproductive lifespan and risk of premature mortality: prospective cohort study. BMJ. 2020;371:m3464. DOI: 10.1136/bmj.m3464
6. Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO classification system (PALM- COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011;113:3-13. DOI:10.1016/j.ijgo.2010.11.011
7. Reavey JJ, Walker C, Murray AA et al. Obesity is associated with heavy menstruation that may be due to delayed endometrial repair. J Endocrinol. 2021;249(2):71-82. DOI: 10.1530/JOE-20-0446
8. Vannuccini S, Jain V, Critchley H, Petraglia F. From menarche to menopause, heavy menstrual bleeding is the underrated compass in reproductive health. Fertil Steril. 2022;118(4):625-36. DOI:10.1016/ j.fertnstert.2022.07.021
9. Critchley HOD, Babayev E, Bulun SE et al. Menstruation: science and Society. Am J Obstet Gynecol. 2020;223:624-64. DOI: 10.1016/ j.ajog.2020.06.004
10. Armstrong GM, Maybin JA, Murray AA et al. Endometrial apoptosis and neutrophil infiltration during menstruation exhibits spatial and temporal dynamics that are recapitulated in a mouse model. Sci Rep. 2017;7(1):17416. DOI: 10.1038/s41598-017-17565-x
11. Jain V, Chodankar RR, Maybin JA, Critchley HOD. Uterine bleeding: how understanding endometrial physiology underpins menstrual health. Nat Rev Endocrinol. 2022;18(5):290-308. DOI: 10.1038 /s41574-021-00629-4
12. Salamonsen LA, Hutchison JC, Gargett CE. Cyclical endometrial repair and regeneration. Development. 2021;148(17):dev199577. DOI: 10.1242/dev.199577
13. Алферова В.И., Мустафина С.В. Распространенность ожирения во взрослой популяции Российской Федерации (обзор литературы). Ожирение и метаболизм. 2022;19(1):96-105. DOI: 10.14341/ omet12809
Alferova V.I., Mustafina S.V. The prevalence of obesity in the adult population of the Russian Federation (literature review). Obesity and metabolism. 2022;19(1):96-105. DOI: 10.14341/omet12809 (in Russian).
14. Артеменко Ю.С., Хамошина М.Б., Петренко Н.В., Демина О.А. Патоморфологические особенности эндометрия при аномальных маточных кровотечениях у пациенток репродуктивного возраста с ожирением. Акушерство и гинекология: новости, мнения, обучение. 2023;11(Спецвыпуск):36-41. DOI: 10.33029/2303-9698-2023-11-suppl-36-41
Artemenko Y.S., Khamoshina M.B., Petrenko N.V., Demina О.А. Pathomorphological features of endometrium in abnormal uterine bleeding in obese patients of reproductive age. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie = Obstetrics and Gynecology: News, Opinions, Training. 2023;11(Supplement):36–41. DOI: 10.33029/ 2303-9698-2023-11-suppl-36-41 (in Russian).
15. Ayhan A, Mao TL, Suryo Rahmanto Y et al. Increased proliferation in atypical hyperplasia/endometrioid intraepithelial neoplasia of the endometrium with concurrent inactivation of ARID1A and PTEN tumour suppressors. J Pathol Clin. Res. 2015;1(3):186-93. DOI: 10.1002/ cjp2.22
16. Mathur R. ARID1A loss in cancer: Towards a mechanistic understanding. Pharmacol Ther. 2018;190:15-23. DOI: 10.1016/j.pharmthera. 2018.05.001
17. Kim TH, Yoo JY, Wang Z et al. ARID1A Is Essential for Endometrial Function during Early Pregnancy. PLoS Genet. 2015;11(9):e1005537. DOI: 10.1371/journal.pgen.1005537
18. Anglesio MS, Papadopoulos N, Ayhan A et al. Cancer-Associated Mutations in Endometriosis without Cancer. N Engl J Med. 2017;376(19):1835-48. DOI: 10.1056/NEJMoa1614814
19. Maybin JA, Murray AA, Saunders PTK et al. Hypoxia and hypoxia inducible factor-1α are required for normal endometrial repair during menstruation. Nat Commun. 2018;9(1):295. DOI: 10.1038/s41467-017-02375-6
20. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11(2):85-97. DOI: 10.1038/nri2921
21. Pararasa C, Bailey CJ, Griffiths HR. Ageing, adipose tissue, fatty acids and inflammation. Biogerontology. 2015;16(2):235-48. DOI: 10.1007/s10522-014-9536-x
22. Murray PJ, Allen JE, Biswas SK et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41(1):14-20. DOI: 10.1016/j.immuni.2014.06.008
23. Uribe-Querol E, Rosales C. Neutrophils Actively Contribute to Obesity-Associated Inflammation and Pathological Complications. Cells. 2022;11(12):1883. DOI: 10.3390/cells11121883
24. Thomas D, Apovian C. Macrophage functions in lean and obese adipose tissue. Metabolism. 2017;72:120-43. DOI: 10.1016/j.metabol.2017.04.005
25. Santander AM, Lopez-Ocejo O, Casas O et al. Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue. Cancers (Basel). 2015;7(1):143-78. DOI: 10.3390/cancers7010143
26. Nteeba J, Ortinau LC, Perfield JW, Keating AF. Diet-induced obesity alters immune cell infiltration and expression of inflammatory cytokine genes in mouse ovarian and peri-ovarian adipose depot tissues. Mol Reprod Dev. 2013;80(11):948-58. DOI: 10.1002/mrd.22231
27. MacKintosh ML, Derbyshire AE, McVey RJ et al. The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk. Int J Cancer. 2019;144(3):641-50. DOI: 10.1002/ ijc.31913
28. Silvestris E, de Pergola G, Rosania R, Loverro G. Obesity as disruptor of the female fertility. Reprod Biol Endocrinol. 2018;16(1):22. DOI: 10.1186/s12958-018-0336-z
29. Onstad MA, Schmandt RE, Lu KH. Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment. J Clin Oncol. 2016;34(35):4225-30. DOI: 10.1200/JCO.2016.69.4638
30. Thrastardottir TO, Copeland VJ, Constantinou C. The Association Between Nutrition, Obesity, Inflammation, and Endometrial Cancer: A Scoping Review. Curr Nutr Rep. 2023;12(1):98-121. DOI: 10.1007/ s13668-022-00447-8
31. Martínez-Aguilar R, Kershaw LE, Reavey JJ et al. HYPOXIA AND REPRODUCTIVE HEALTH: The presence and role of hypoxia in the endometrium. Reproduction. 2021;161(1):F1-F17. DOI: 10.1530/REP-20-0268
32. Mahiddine K, Blaisdell A, Ma S et al. Relief of tumor hypoxia unleashes the tumoricidal potential of neutrophils. J Clin Invest. 2020;130(1): 389-403. DOI: 10.1172/JCI130952

For citation:Khamoshina M.B., Tolibova G.Kh., Tral T.G., Artemenko Yu.S. ARID1a expression in the endometrium of women of reproductive age with abnormal uterine bleeding and obesity. Clinical review for general practice. 2024; 5 (4): 46–52 (In Russ.). DOI: 10.47407/kr2024.5.4.00418


All accepted articles publish licensed under a Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

  • About
  • Editorial board
  • Ethics
  • For authors
  • Author fees
  • Peer review
  • Contacts

oa
crossref
анри


  Indexing

doaj
elibrary

Address of the Editorial Office:

127055, Moscow, s/m 37

Correspondence address:

115054, Moscow, Zhukov passage, 19, fl. 2, room XI


Managing Editor:

+7 (495) 926-29-83

id@con-med.ru