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ENDOMETRIAL CELLS APOPTOSIS IN HEALTH AND PROLIFERATIVE DISEASES OF THE UTERUS

Abstract

The article presents the literature data on the regulation of endometrial cells apoptosis in health and proliferative diseases of the uterus. It is noted that throughout the menstrual cycle the cells apoptosis and regeneration take place in strictly controlled sequence and depend on the phase of the cycle and hormonal changes. The expression of Bcl-2 (inhibitor of apoptosis) in cells also varies cyclically in endometrial glandular cells, peaking in the late proliferative phase, and then decreasing to a minimum at the end of the secretory phase and within the menstruation phase. In endometriosis, the apoptosis index in endometrial functional layer is significantly lower than in healthy women. The weakened apoptosis is associated with the disturbance of its regulation. The expression of Bcl-2 increased with the progress of the disease in the endometrial tissue, while the expression of bax (apoptosis activator) corresponded to figures in healthy women. The increase in the expression of Bcl-2 was observed in the cells of myomatous fibroids. Thus, in patients with uterine myoma the ratio Bcl-2/Bax is more important. It is noted that the weakened apoptosis of endometrial cells and disorders of apoptosis regulation are leading pathogenic mechanisms for the development of proliferative diseases of the uterus. This is the basis of a new search for the effective diagnosis, prognosis and treatment of this widespread disease.

About the Authors

N. V. Borovkova
N.V. Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department
Russian Federation
Moscow


M. M. Damirov
N.V. Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department
Russian Federation
Moscow


O. N. Oleynikova
N.V. Sklifosovsky Research Institute for Emergency Medicine of the Moscow Healthcare Department
Russian Federation
Moscow


References

1. Strizhakov A.N., Davydov A.I., Pashkov V.M. Dobrokachestvennye zabolevaniya matki [Benign uterine diseases]. Moscow: GEOTAR-Media Publ., 2011. 288 p. (In Russian).

2. Damirov M.M., Oleynikova O.N., Mayorova O.V. Genital’nyy endometrioz: vzglyad praktikuyushchego vracha [Genital endometriosis: a view of the practitioner]. Moscow: BINOM Publ., 2013. 152 p. (In Russian)

3. Reznikova N.N. Uchastie apoptoza v patogeneze vnutrennego endometrioza tela matki: dis. ... kand. med. nauk [The involvement of apoptosis in the pathogenesis of internal endometriosis of uterine body: Cand. med. sci. diss. synopsis]. Moscow, 2003. 112 p. (In Russian).

4. Sidorova I., Kogan E., Zayrat’yants O., et al. Rol’ protsessov apoptoza i proliferatsii v patogeneze prostoy i proliferiruyushchey miomy matki v sochetanii s adenomiozom [Role of apoptosis and proliferation in the pathogenesis of simple and proliferating uterine fibroids in combination with adenomyosis].Vrach. 2006; 14: 8–12. (In Russian).

5. Chapel H., Haeney M., Misbah S., Snowden N. Essentials of Clinical Immunology. 5th ed. Wiley-Blackwell, 2006. 368 p. (Russ. ed.: Chepel’ E., Kheyni M., Misbakh S., Snovden N. Osnovy klinicheskoy immunologii. Moscow: GEOTAR-Media Publ., 2008. 416 p.)

6. Yarilin A.A. Osnovy immunologii [Fundamentals of immunology]. Moscow: Meditsina Publ., 1999. 608 p. (In Russian).

7. Pal’tsev M.A. Molekulyarnaya meditsina i progress fundamental’nykh nauk [Molecular medicine and advances in fundamental Sciences]. Vestnik RAN. 2002; 1: 13–21. (In Russian).

8. Man’ko V.M., Devrishov D.A. Veterinarnaya immunologiya. Fundamental’nye osnovy [Veterinary Immunology. Fundamentals]. Moscow: Agrovet Publ., 2011. 752 p. (In Russian).

9. Kerr J.F., Wyllie A.H., Currie A.R. Apoptosis: a basic biological phenomen with wide-ranging implications in tissue kinetics. Brit J Cancer. 1972; 26 (4): 239–257.

10. Taniguchi F., Kaponis A., Izawa M., et al. Apoptosis and endometriosis. Front Biosci (Elite Ed). 2011; 1 (3): 648–662.

11. Wang Sh., El-Deiry W.S. TRAIL and apoptosis induction by TNF-family death receptors. Oncogene. 2003; 22: 8628–8633.

12. Atasoy P., Bozdoğan O., Erekul S., et al. Fas-mediated pathway and apoptosis in normal, hyperplastic, and neoplastic endometrium. Gynecol oncology. 2003; 91(2): 309–317.

13. Kuwana T., Newmeyer D.D. Bcl-2-family proteins and the role of mitochondria in apoptosis. Curr Opin Cell Biol. 2003; 15: 1–9.

14. Burbank F. Fibroids, menstruation, childbirth, and evolution: the fascinating story of uterine blood vessels. Wheatmark (USA), 2009. 296 р.

15. Nikolaenko S.A., Reva G.V. Rol’ apoptoza i proliferatsii v patogeneze zabolevaniy sheyki matki u zhenshchin reproduktivnogo vozrasta [The role of apoptosis and proliferation in the pathogenesis of cervical disease in women of reproductive age]. Sovremennye naukoemkie tekhnologii. 2004; 5: 66–67. (In Russian)

16. Bozdoğan O., Atasoy P., Erekul S., et al. Apoptosis-related proteins and steroid hormone receptors in normal, hyperplastic, and neoplastic endometrium. Int J Gynecol Pathol. 2002; 21 (4): 375–382.

17. Reis F.M., Petraglia F., Taylor R.N. Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis. Hum Reproduct Update. 2013; 19 (4): 406–418.

18. Rogers P.A., Lederman F., Plunkett D., Affandi B. Bcl-2, Fas, and caspase 3 expression in endometrium from levonorgestrel implant users with and without breakthrough bleeding. Hum Reproduct Update. 2000; 15 Suppl 3: 152–161.

19. Korkmaz D., Bastu E., Dural O., et al. Apoptosis through regulation of Bcl-2, Bax and Mcl-1 expressions in endometriotic cyst lesions and the endometrium of women with moderate to severe endometriosis. Obstet Gynaecol. 2013; 33 (7): 725–728.

20. Tilly J.L., Tilly K., Kenton M.L., Johnson A.L. Expression of members of the bcl-2 gene family in the immature rat ovary: equine chorionic gonadotropin-mediated inhibition of granulosa cell apoptosis is associated with decreased bax and constitutive bcl-2 and bcl-xlong messenger ribonucleic acid levels. Endocrinology. 1995; 136 (1): 232–241.

21. LaVoie H.A., Witorsch R.J. Investigation of intracellular signals mediating the antiapoptotic action of prolactin in Nb2 lymphoma cells. Proc Soc Exp Biol Med. 1995; 209 (3): 257–269.

22. Olovsson M., Burlev V.A., Volkov N.I., et al. Kletochnaya proliferatsiya, apoptoz i retseptory k steroidnym gormonam u bol’nykh s miomoy matki [Cell proliferation, apoptosis, and steroid hormone receptors in patients with hysteromyoma]. Akusherstvo i ginekologiya. 2005; 4: 23–28. (In Russian).

23. Voytkova V.V. Izuchenie apoptoza metodom protochnoy tsitofluorimetrii (obzor literatury) [Study of apoptosis by flow-cytometry (literature review)]. Byulleten’ Vostochno-Sibirskogo nauchnogo tsentra SO RAMN. 2010; 6-1: 220–225. (In Russian).

24. Khaydukov S.V., Zurochka A.V., eds. Voprosy sovremennoy protochnoy tsitometrii. Klinicheskoe primenenie [Issues of modern flow cytometry. Clinical application]. Chelyabinsk, 2008. 195 p. (In Russian).

25. Sukhikh G.T., Chernukha G.E., Smetnik V.P., et al. Proliferativnaya aktivnost’ i apoptoz v giperplazirovannom endometrii [Proliferative activity and apoptosis in hyperplastic endometrium]. Akusherstvo i ginekologiya. 2005; 5: 25–29. (In Russian).

26. Salmassi A., Acar-Perk B., Schmutzler A.G., et al. Apoptosis Resistance in Endometriosis. Bioimpacts. 2011; 1 (2): 129–134.

27. Roshangar L., Abdollahifard S., Majdi A., et al. Study of ultrastructure and apoptosis in the endometrium of women with or without endometriosis. Iran J Reprod Med. 2013; 11 (5): 399–404.

28. Belokrinitskaya T.E., Vitkovskiy Yu.A., Ponomareva Yu.N., et al. Faktor nekroza opukholey a i transformiruyushchiy faktor rosta b v regulyatsii apoptoza i proliferatsii kletok pri displazii i rake sheyki matki [The tumor necrosis factor a and transforming growth factor b in regulation of apoptosis and cell proliferation in dysplasia and cervical cancer]. Tsitokiny i vospalenie. 2006; 5 (1): 31–33. (In Russian).

29. Dmowski W.P., Ding J., Shen J., et al. Apoptosis in endometrial glandular and stromal cells in women with and without endometriosis. Hum Rep Update. 2001; 16 (9): 1802–1808.

30. Sotnikova N.Yu., Antsiferova Yu.S., Posiseeva L.V., et al. Izmenenie invazivnykh svoystv endometrial’nykh stromal’nykh kletok pri endometrioze [Change in invasive properties of endometrial stromal cells in endometriosis]. Immunologiya. 2007; 1: 34–37.

31. Agic A., Djalali S., Diedrich K., Hornung D. Apoptosis in endometriosis. Gynecol Obstet Invest. 2009; 68 (4): 217–223.

32. Sturlese E., Salmeri F.M., Retto G., et al. Dysregulation of the Fas/FasL system in mononuclear cells recovered from peritoneal fluid of women with endometriosis. Reprod Immunol. 2011; 92 (1–2): 74–81.

33. Meresman G.F., Vighi S., Buquet R.A., et al. Apoptosis and expression of Bcl-2 and Bax in eutopic endometrium from women with endometriosis. Fertil Steril. 2000; 74 (4): 760–766.

34. Uegaki T., Taniguchi F., Nakamura K., et al. Inhibitor of apoptosis proteins (IAPs) may be effective therapeutic targets for treating endometriosis. Hum Rep Update. 2015; 30 (1): 149–158.

35. Nguyen H., Syed V. Progesterone inhibits growth and induces apoptosis in cancer cells through modulation of reactive oxygen species. Gynecol Endocrinol. 2011; 27: 830–836.

36. Yamanaka A., Kimura F., Kishi Y., et al. Progesterone and synthetic progestin, dienogest, induce apoptosis of human primary cultures of adenomyotic stromal cells. Eur J Obstet Gynecol Reprod Biol. 2014; 179: 170–174.

37. Shimizu Y., Mita S., Takeuchi T., et al. Dienogest, a synthetic progestin, inhibits prostaglandin E2 production and aromatase expression by human endometrial epithelial cells in a spheroid culture system. Steroids. 2011; 76 (1–2): 60–67.

38. Demina T.N., Chayka K.V., Zhikharskiy R.V. Vliyanie biologicheskogo deystviya progesterona na protsessy apoptoza v miomatoznykh uzlakh u zhenshchin reproduktivnogo vozrasta [The influence of biological actions of progesterone on apoptosis in myomatous nodes in women of reproductive age]. Mediko-sotsial’nye problemy sem’i. 2013; 2. Available at: http://www.mif-ua.com/archive/article/36458. (Accessed April 28, 2016). (In Russian).

39. Mizutani T., Sugihara A., Nakamuro K., Terada N. Suppression of cell proliferation and induction of apoptosis in uterine leiomyoma by gonadotropin-releasing hormone agonist (leuprolide acetate). J Clin Endocrinol Metab. 1998; 83 (4): 1253–1255.


Review

For citations:


Borovkova N.V., Damirov M.M., Oleynikova O.N. ENDOMETRIAL CELLS APOPTOSIS IN HEALTH AND PROLIFERATIVE DISEASES OF THE UTERUS. Russian Sklifosovsky Journal "Emergency Medical Care". 2016;(2):48-53. (In Russ.)

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