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Melkozerova O.A.

Ural Research Institute for Maternity and Child Care, Ministry of Public Health of the Russian Federation

Okulova E.O.

Ural Scientific Research Institute of Maternity and Child Care Public Health’s Ministry of the Russian Federation

Mikhelson A.A.

Ural Scientific Research Institute of Maternity and Child Care Public Health’s Ministry of the Russian Federation

Chistyakova G.N.

Ural Research Institute for Maternity and Child Care, Ministry of Public Health of the Russian Federation

Grishkina A.A.

Ural Research Institute for Maternity and Child Care, Ministry of Public Health of the Russian Federation

Limanovskaya O.V.

Ural Federal University named after the first President of Russia B.N. Yeltsin

Glukhov A.S.

Ural Federal University named after the first President of Russia B.N. Yeltsin

Duhovich A.S.

Ural Federal University named after the first President of Russia B.N. Yeltsin

Molecular-biological mechanisms of ovarian reserve reduction after surgical treatment of deep infiltrative endometriosis

Authors:

Melkozerova O.A., Okulova E.O., Mikhelson A.A., Chistyakova G.N., Grishkina A.A., Limanovskaya O.V., Glukhov A.S., Duhovich A.S.

More about the authors

Journal: Russian Journal of Human Reproduction. 2022;28(3): 43‑53

DOI: 10.17116/repro20222803143

Read: 1562 times

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Table of contents

MOLECULAR-BIOLOGICAL MECHANISMS OF OVARIAN RESERVE REDUCTION AFTER SURGICAL TREATMENT OF DEEP INFILTRATIVE ENDOMETRIOSIS
MOLECULAR-BIOLOGICAL MECHANISMS OF OVARIAN RESERVE REDUCTION AFTER SURGICAL TREATMENT OF DEEP INFILTRATIVE ENDOMETRIOSIS

To cite this article:

Melkozerova OA, Okulova EO, Mikhelson AA, et al. . Molecular-biological mechanisms of ovarian reserve reduction after surgical treatment of deep infiltrative endometriosis. Russian Journal of Human Reproduction. 2022;28(3):43‑53. (In Russ.)
https://doi.org/10.17116/repro20222803143

 
Подписка 2026 Проблемы репродукции (Russian Journal of Human Reproduction)
 
МСФ на ЯМ
Использование инфографики авторами научных работ
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Abstract:

PURPOSE OF THE STUDY

To study the molecular biological mechanisms of the decrease in ovarian reserve after surgical treatment of deep infiltrative endometriosis in patients of reproductive age.

MATERIALS AND METHODS

A prospective cohort comparative study was carried out. The main group consisted of 70 patients of reproductive age who underwent surgical treatment of deep infiltrative endometriosis (DIE), the comparison group consisted of 50 fertile patients who underwent uterine plastic surgery. All patients underwent an assessment of ovarian reserve before and 6 months after surgical treatment. An immunohistochemical study was performed to determine the level of expression of estrogen receptors, regulators of apoptosis (p53, Bcl-2, AKT, PTEN) and angiogenesis (VEGF R1) in the follicle granulosa of the ovarian biopsy, as well as in the epithelium of the glands and stroma of endometrioid lesions.

RESULTS

When assessing the state of the ovarian reserve, it was found that the level of AMH at the preoperative stage was significantly lower in patients with HIE (2.4±2.0 ng/ml) than in patients of the comparison group (3.6±2.9 ng/ml), p<0.05. Six months after the surgical treatment of DIE, there was a significant decrease in the level of AMH (1.7±1.5 ng/ml) compared with the baseline (2.4±2.0 ng/ml), p<0.05.

A decrease in ovarian reserve in patients with HIE was associated with a reduced expression of estrogen receptors in the ovarian granulosa tissue, which indicates the formation of ovarian hormonal resistance in this disease. In the cortical tissue of the ovaries in patients of the first group, there was a decrease in the expression of PTEN and an increase in the expression of AKT compared to the second group, which indicates the activation of the anti-apoptotic signaling pathway PI3K/Akt/mTOR in endometriosis. On the other hand, there is a weakening of Bcl-2 expression and an increase in p53 expression in ovarian granulosa tissue in patients of the first group with a significant postoperative decrease in ovarian reserve.

CONCLUSION

Activation of the anti-apoptotic signaling pathway PI3K/Akt/mTOR plays a significant role in the decrease in ovarian reserve after surgical treatment of DIE, contributing to the premature depletion of primordial follicles. Compensating for the increased proliferative activity, the ovarian cortex is sensitized to p53-associated apoptosis, which leads to the formation of a vicious pathogenetic circle and the irreversible loss of the follicular reserve. This dictates the need to timely address the issue of surgical treatment of patients of reproductive age with HIE in terms of maintaining the ovarian reserve.

Keywords:

angiogenesis
apoptosis
infertility
deep infiltrative endometriosis
ovarian reserve
surgical treatment
estrogen receptors

Authors:

Melkozerova O.A.

Ural Research Institute for Maternity and Child Care, Ministry of Public Health of the Russian Federation

Okulova E.O.

Ural Scientific Research Institute of Maternity and Child Care Public Health’s Ministry of the Russian Federation

Mikhelson A.A.

Ural Scientific Research Institute of Maternity and Child Care Public Health’s Ministry of the Russian Federation

Chistyakova G.N.

Ural Research Institute for Maternity and Child Care, Ministry of Public Health of the Russian Federation

Grishkina A.A.

Ural Research Institute for Maternity and Child Care, Ministry of Public Health of the Russian Federation

Limanovskaya O.V.

Ural Federal University named after the first President of Russia B.N. Yeltsin

Glukhov A.S.

Ural Federal University named after the first President of Russia B.N. Yeltsin

Duhovich A.S.

Ural Federal University named after the first President of Russia B.N. Yeltsin

Received:

30.03.2022

Accepted:

13.05.2022

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References:

  1. Endometrioz. Klinicheskie rekomendacii. 2020. Odobreny Nauchno-prakticheskim Sovetom Minzdrava Rossii. Accessed April 27, 2022. (In Russ.). https://cr.minzdrav.gov.ru/recomend/259_1?
  2. Ashrafi M, Arabipoor A, Hemat M, Salman-Yazdi R. The impact of the localisation of endometriosis lesions on ovarian reserve and assisted reproduction techniques outcomes. Journal of Obstetrics and Gynaecology. 2019;39(1):91-97.  https://doi.org/10.1080/01443615.2018.1465898
  3. Romanski PA, Brady PC, Farland LV, Thomas AM, Hornstein MD. The effect of endometriosis on the antimüllerian hormone level in the infertile population. Journal of Assisted Reproduction and Genetics. 2019;36(6):1179-1184. https://doi.org/10.1007/s10815-019-01450-9
  4. Laganà AS, Garzon S, Götte M, Viganò P, Franchi M, Ghezzi F, Martin DC. The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights. International Journal of Molecular Sciences. 2019;20(22):5615. https://doi.org/10.3390/ijms20225615
  5. Istrate-Ofiţeru AM, Pirici D, Niculescu M, Berceanu C, Berceanu S, Voicu NL, Piringă GD, Roşu GC, Iovan L, Căpitănescu RG, Diţescu D, Sava A, Mogoantă L, Neacşu A. Clinical, morphological and immunohistochemical survey in different types of endometriosis. Romanian Journal of Morphology and Embryology. 2018; 59(4):1133-1153.
  6. Mori T, Ito F, Koshiba A, Kataoka H, Takaoka O, Okimura H, Khan KN, Kitawaki J. Local estrogen formation and its regulation in endometriosis. Reproductive Medicine and Biology. 2019;18(4): 305-311.  https://doi.org/10.1002/rmb2.12285
  7. Koninckx PR, Ussia A, Adamyan L, Gomel V, Martin DC. Peritoneal fluid progesterone and progesterone resistance in superficial endometriosis lesions. Human Reproduction. 2022;37(2):203-211.  https://doi.org/10.1093/humrep/deab258
  8. Lenz J, Chvatal R, Fiala L, Konecna P, Lenz D. Comparative immunohistochemical study of deep infiltrating endometriosis, lymph node endometriosis and atypical ovarian endometriosis including description of a perineural invasion. Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2021; 165(1):69-79.  https://doi.org/10.5507/bp.2020.006
  9. Sroyraya M, Songkoomkrong S, Changklungmoa N, Poljaroen J, Weerakiet S, Sophonsritsuk A, Wongkularb A, Lertvikool S, Tingthanatikul Y, Sobhon P. Differential expressions of estrogen and progesterone receptors in endometria and cyst walls of ovarian endometrioma from women with endometriosis and their responses to depo-medroxyprogesterone acetate treatment. Molecular and Cellular Probes. 2018;40:27-36.  https://doi.org/10.1016/j.mcp.2018.07.001
  10. Maekawa R, Mihara Y, Sato S, Okada M, Tamura I, Shinagawa M, Shirafuta Y, Takagi H, Taketani T, Tamura H, Sugino N. Aberrant DNA methylation suppresses expression of estrogen receptor 1 (ESR1) in ovarian endometrioma. Journal of Ovarian Research. 2019;12(1):14.  https://doi.org/10.1186/s13048-019-0489-1
  11. Kalkan U, Biyik I, Simsek S. T-Cadherin, E-Cadherin, PR-α, and ER-α Levels in Deep Infiltrating Endometriosis. International Journal of Gynecological Pathology. 2022;10.1097/PGP.0000000000000860. https://doi.org/10.1097/PGP.0000000000000860
  12. Varga J, Reviczká A, Háková H, Švajdler P, Rabajdová M, Ostró A. Predictive factors of endometriosis progression into ovarian cancer. Journal of Ovarian Research. 2022;15(1):5.  https://doi.org/10.1186/s13048-021-00940-8
  13. Delbandi AA, Mahmoudi M, Shervin A, Heidari S, Kolahdouz-Mohammadi R, Zarnani AH. Evaluation of apoptosis and angiogenesis in ectopic and eutopic stromal cells of patients with endometriosis compared to non-endometriotic controls. BMC Womens Health. 2020;20(1):3.  https://doi.org/10.1186/s12905-019-0865-4
  14. Duan R, Wang Y, Lin A, Lian L, Cao H, Gu W, Li T, Sun Q. Expression of nm23-H1, p53, and integrin β1 in endometriosis and their clinical significance. International Journal of Clinical and Experimental Pathology. 2020;13(5):1024-1029.
  15. Di Nisio V, Rossi G, Di Luigi G, Palumbo P, D’Alfonso A, Iorio R, Cecconi S. Increased levels of proapoptotic markers in normal ovarian cortex surrounding small endometriotic cysts. Reproductive Biology. 2019;19(3):225-229.  https://doi.org/10.1016/j.repbio.2019.08.002
  16. Chen L, Ni Z, Cai Z, Cheng W, Sun S, Yu C, JinYu. The Mechanism Exploration of Follicular Fluids on Granulose Cell Apoptosis in Endometriosis-Associated Infertility. BioMed Research International. 2021;2021:6464686. https://doi.org/10.1155/2021/6464686
  17. Zhou S, Xi Y, Chen Y, Wu T, Yan W, Li M, Wu M, Luo A, Shen W, Xiang T, Wang S. The inhibition of WIP1 phosphatase accelerates the depletion of primordial follicles. Reproductive Biomedicine Online. 2021;43(2):161-171.  https://doi.org/10.1016/j.rbmo.2021.05.007
  18. Kim SY, Nair DM, Romero M, Serna VA, Koleske AJ, Woodruff TK, Kurita T. Transient inhibition of p53 homologs protects ovarian function from two distinct apoptotic pathways triggered by anticancer therapies. Cell Death and Differentiation. 2019;26(3):502-515.  https://doi.org/10.1038/s41418-018-0151-2
  19. Bellusci G, Mattiello L, Iannizzotto V, Ciccone S, Maiani E, Villani V, Diederich M, Gonfloni S. Kinase-independent inhibition of cyclophosphamide-induced pathways protects the ovarian reserve and prolongs fertility. Cell Death and Disease. 2019;10(10):726.  https://doi.org/10.1038/s41419-019-1961-y
  20. Vo KCT, Kawamura K. In Vitro Activation Early Follicles: From the Basic Science to the Clinical Perspectives. International Journal of Molecular Sciences. 2021;22(7):3785. https://doi.org/10.3390/ijms22073785
  21. Lv Y, Cao RC, Liu HB, Su XW, Lu G, Ma JL, Chan WY. Single-Oocyte Gene Expression Suggests That Curcumin Can Protect the Ovarian Reserve by Regulating the PTEN-AKT-FOXO3a Pathway. International Journal of Molecular Sciences. 2021;22(12):6570. https://doi.org/10.3390/ijms22126570
  22. Terren C, Nisolle M, Munaut C. Pharmacological inhibition of the PI3K/PTEN/Akt and mTOR signalling pathways limits follicle activation induced by ovarian cryopreservation and in vitro culture. Journal of Ovarian Research. 2021;14(1):95.  https://doi.org/10.1186/s13048-021-00846-5
  23. Takeuchi A, Koga K, Satake E, Makabe T, Taguchi A, Miyashita M, Takamura M, Harada M, Hirata T, Hirota Y, Yoshino O, Wada-Hiraike O, Fujii T, Osuga Y. Endometriosis triggers excessive activation of primordial follicles via PI3K-PTEN-Akt-Foxo3 pathway. The Journal of Clinical Endocrinology and Metabolism. 2019;104(11): 5547-5554. https://doi.org/10.1210/jc.2019-00281
  24. Barra F, Ferro Desideri L, Ferrero S. Inhibition of PI3K/AKT/mTOR pathway for the treatment of endometriosis. British Journal of Pharmacology. 2018;175(17):3626-3627. https://doi.org/10.1111/bph.14391
  25. Tang T, Lai H, Huang X, Gu L, Shi H. Application of serum markers in diagnosis and staging of ovarian endometriosis. The Journal of Obstetrics and Gynaecology Research. 2021;47(4):1441-1450. https://doi.org/10.1111/jog.14654
  26. Korchagina AA, Shein SA, Gurina OI, Chekhonin VP. The role of VEGFR receptors in neoplastic angiogenesis and prospects for therapy of brain tumors. Vestnik Rossijskoj akademii medicinskih nauk. 2013;68(11):104-114. (In Russ.). https://doi.org/10.15690/vramn.v68i11.851
  27. Lal N, Puri K, Rodrigues B. Vascular Endothelial Growth Factor B and Its Signaling. Frontiers in Cardiovascular Medicine. 2018;5:39.  https://doi.org/10.3389/fcvm.2018.00039
  28. Ling M, Quan L, Lai X, Lang L, Li F, Yang X, Fu Y, Feng S, Yi X, Zhu C, Gao P, Zhu X, Wang L, Shu G, Jiang Q, Wang S. VEGFB Promotes Myoblasts Proliferation and Differentiation through VEGFR1-PI3K/Akt Signaling Pathway. International Journal of Molecular Sciences. 2021;22(24):13352. https://doi.org/10.3390/ijms222413352
  29. Vodolazkaia A, Yesilyurt BT, Kyama CM, Bokor A, Schols D, Huskens D, Meuleman C, Peeraer K, Tomassetti C, Bossuyt X, Lambrechts D, D’Hooghe T, Fassbender A. Vascular endothelial growth factor pathway in endometriosis: genetic variants and plasma biomarkers. Fertility and Sterility. 2016;105(4):988-996.  https://doi.org/10.1016/j.fertnstert.2015.12.016
  30. Hattori K, Ito Y, Honda M, Sekiguchi K, Hosono K, Shibuya M, Unno N, Majima M. Lymphangiogenesis induced by vascular endothelial growth factor receptor 1 signaling contributes to the progression of endometriosis in mice. Journal of Pharmacological Sciences. 2020;143(4):255-263.  https://doi.org/10.1016/j.jphs.2020.05.003
  31. Sekiguchi K, Ito Y, Hattori K, Inoue T, Hosono K, Honda M, Numao A, Amano H, Shibuya M, Unno N, Majima M. VEGF Receptor 1-Expressing Macrophages Recruited from Bone Marrow Enhances Angiogenesis in Endometrial Tissues. Scientific Reports. 2019;9(1):7037. https://doi.org/10.1038/s41598-019-43185-8
  32. Wu WB, Chen HT, Lin JJ, Lai TH. VEGF Concentration in a Preovulatory Leading Follicle Relates to Ovarian Reserve and Oocyte Maturation during Ovarian Stimulation with GnRH Antagonist Protocol in In Vitro Fertilization Cycle. Journal of Clinical Medicine. 2021;10(21):5032. https://doi.org/10.3390/jcm10215032
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