The effect of 8 weeks of swimming training and stem cell injection on some effective factors in the angiogenesis pathway of premature ovarian failure model rats

Document Type : Original Article

Authors

1 PhD student in Exercise Physiology, Department of Exercise Physiology, School of Humanities, Sari Branch, Islamic Azad University, Sari, Iran.

2 Associate Professor, Department of Exercise Physiology, School of Humanities, Sari Branch, Islamic Azad University, Sari, Iran.

3 Assistant Professor, Department of Exercise Physiology, School of Humanities, Sari Branch, Islamic Azad University, Sari, Iran.

4 Assistant Professor, Department of Biological Sciences and Technologies, School of Medical Sciences, Sari Branch, Islamic Azad University, Sari, Iran.

Abstract

Introduction: Female infertility is a universal medical condition that can be caused by various disorders of the reproductive system, including premature ovarian failure. The present study was performed with aim to investigate the effect of 8 weeks of swimming training and stem cell injection on VEGF, TGF and HGF genes in the ovarian tissue of premature ovarian failure model rats.
Methods: In this experimental research, 30 female rats 6- to 8-week-old were selected. In order to create a model of premature ovarian failure, cyclophosphamide and biosulfan were used in the amount of 100 and 50 mg/kg, respectively, as an intraperitoneal injection. After model induction, rats were randomly divided into 6 groups (5 heads in each group) including: 1) healthy control, 2) patient+ sham, 3) patient+ saline, 4) patient+ cell, 5) patient +exercise and 6) patient+ cell+ exercise. The rats of the training group swam for 8 weeks. Cell groups, 2 weeks after creating the model stem cells were transplanted in the ovary at the rate of one million cells for each mouse. Data analysis was done using SPSS statistical software (version 22) and one-way ANOVA and Tukey's post hoc tests. P≤0.05 was considered significant.
Results: Induction of premature ovarian failure led to a significant increase in VEGF, TGF and HGF genes in the ovarian tissue of rats compared to the control-healthy group (P≤0.05) that the exercise, cell and exercise+ cell groups decreased the expression of these genes compared to the patient and patient-saline groups (P≤0.05).
Conclusion: The synergistic effect of aerobic exercise and bone marrow-derived mesenchymal stem cells improve angiogenic factors in experimental premature ovarian failure model rats.

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  1. Esfandyari S, Chugh RM, Park HS, Hobeika E, Ulin M, Al-Hendy A. Mesenchymal stem cells as a bio organ for treatment of female infertility. Cells 2020; 9(10):2253.
  2. Zhang C. The roles of different stem cells in premature ovarian failure. Current stem cell research & therapy 2020; 15(6):473-81.
  3. Chen L, Guo S, Wei C, Li H, Wang H, Xu Y. Effect of stem cell transplantation of premature ovarian failure in animal models and patients: a meta-analysis and case report. Experimental and therapeutic medicine 2018; 15(5):4105-18.
  4. Li N, Yang C, Xie H, Liu Y, Liao Y. Effects of aerobic exercise on rats with hyperandrogenic polycystic ovarian syndrome. International Journal of Endocrinology 2021; 2021.
  5. Walters KA, Bertoldo MJ, Handelsman DJ. Evidence from animal models on the pathogenesis of PCOS. Best Practice & Research Clinical Endocrinology & Metabolism 2018; 32(3):271-81.
  6. Fuertes-Martin R, Moncayo S, Insenser M, Martínez-García MA, Luque-Ramirez M, Grau NA, et al. Glycoprotein A and B height-to-width ratios as obesity-independent novel biomarkers of low-grade chronic inflammation in women with polycystic ovary syndrome (PCOS). Journal of proteome research 2019; 18(11):4038-45.
  7. Lee BC, Lee J. Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2014; 1842(3):446-62.
  8. Suzuki K. Chronic inflammation as an immunological abnormality and effectiveness of exercise. Biomolecules 2019; 9(6):223.
  9. Wu C, Jiang F, Wei K, Lin F, Jiang Z. Effects of exercise combined with finasteride on hormone and ovarian function in polycystic ovary syndrome rats. International Journal of Endocrinology 2019; 2019.
  10. Lin J, Wu D, Jia L, Liang M, Liu S, Qin Z, et al. The treatment of complementary and alternative medicine on premature ovarian failure. Evidence-Based Complementary and Alternative Medicine 2021; 2021.
  11. Li XT, Li PY, Liu Y, Yang HS, He LY, Fang YG, et al. Health-related quality-of-life among patients with premature ovarian insufficiency: a systematic review and meta-analysis. Quality of Life Research 2020; 29:19-36.
  12. Felix AC, Dutra SG, Gastaldi AC, Bonfim PC, Vieira S, de Souza HC. Physical training promotes similar effects to the blockade of angiotensin-converting enzyme on the cardiac morphology and function in old female rats subjected to premature ovarian failure. Experimental Gerontology 2018; 109:90-8.
  13. Santos WL, da Silva Pinheiro C, de Oliveira Santos R, da Silva AC, Severo JS, Mendes PH, et al. Physical exercise alleviates oxidative stress in brown adipose tissue and causes changes in body composition and nutritional behavior in rats with polycystic ovary syndrome. Life Sciences 2023; 325:121754.
  14. Naji A, Rouas-Freiss N, Durrbach A, Carosella ED, Sensébé L, Deschaseaux F. Concise review: combining human leukocyte antigen G and mesenchymal stem cells for immunosuppressant biotherapy. Stem cells 2013; 31(11):2296-303.
  15. Fan XL, Zhang Y, Li X, Fu QL. Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cellular and molecular life sciences 2020; 77:2771-94.
  16. Rungsiwiwut R, Virutamasen P, Pruksananonda K. Mesenchymal stem cells for restoring endometrial function: An infertility perspective. Reproductive Medicine and Biology 2021; 20(1):13-9.
  17. Harrell CR, Fellabaum C, Jovicic N, Djonov V, Arsenijevic N, Volarevic V. Molecular mechanisms responsible for therapeutic potential of mesenchymal stem cell-derived secretome. Cells 2019; 8(5):467.
  18. Ling L, Feng X, Wei T, Wang Y, Wang Y, Wang Z, et al. Human amnion-derived mesenchymal stem cell (hAD-MSC) transplantation improves ovarian function in rats with premature ovarian insufficiency (POI) at least partly through a paracrine mechanism. Stem cell research & therapy 2019; 10:1-8.
  19. Zhao YX, Chen SR, Su PP, Huang FH, Shi YC, Shi QY, et al. Using mesenchymal stem cells to treat female infertility: an update on female reproductive diseases. Stem cells international 2019;
  20. Montenegro ML, Bonocher CM, Meola J, Portella RL, Ribeiro-Silva A, Brunaldi MO, et al. Effect of physical exercise on endometriosis experimentally induced in rats. Reproductive Sciences 2019; 26(6):785-93.
  21. Abedy Ghehi F, Fathi R, Abtahi NS, Eivazkhani F, Bahrehbar K, Abed Heidari E, et al. Germ cells Markers Expression in Mouse Premature Ovarian Failure Model. Pathobiology Research 2019; 22(3):149-57.
  22. Shahidian Akbar F, Farzanegi P, Abbaszadeh H. Effect of a period of swimming exercise and vitamin E intake on catalase and superoxide dismutase activity, and malondialdehyde levels in ovarian tissue of endometriosis model rats. The Iranian Journal of Obstetrics, Gynecology and Infertility 2020; 23(9):43-51.
  23. Ticinesi A, Lauretani F, Tana C, Nouvenne A, Ridolo E, Meschi T. Exercise and immune system as modulators of intestinal microbiome: implications for the gut-muscle axis hypothesis. Exercise immunology review 2019;
  24. Benham JL, Yamamoto JM, Friedenreich CM, Rabi DM, Sigal RJ. Role of exercise training in polycystic ovary syndrome: a systematic review and meta‐analysis. Clinical obesity 2018; 8(4):275-84.
  25. Dyck DJ. Adipokines as regulators of muscle metabolism and insulin sensitivity. Applied Physiology, Nutrition, and Metabolism 2009; 34(3):396-402.
  26. Tremblay A, Dutheil F, Drapeau V, Metz L, Lesour B, Chapier R, et al. Long-term effects of high-intensity resistance and endurance exercise on plasma leptin and ghrelin in overweight individuals: The RESOLVE Study. Applied physiology, nutrition, and metabolism 2019; 44(11):1172-9.
  27. Moro T, Tinsley G, Bianco A, Marcolin G, Pacelli QF, Battaglia G, et al. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males. Journal of translational medicine 2016; 14(1):1-10.
  28. Frühbeck G, Catalán V, Rodríguez A, Gómez-Ambrosi J. Adiponectin-leptin ratio: a promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk. Adipocyte 2018; 7(1):57-62.
  29. Tojek K, Anaszewicz M, Szukay B, Czerniak B, Socha E, Lis K, et al. Circulating leptin, adiponectin, and tumor necrosis factor-alpha in patients undergoing surgery due to colorectal cancer. Digestion 2021; 102(2):246-55.
  30. Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell stem cell 2015; 17(1):11-22.
  31. Wang ZB, Hao JX, Meng TG, Guo L, Dong MZ, Fan LH, et al. Transfer of autologous mitochondria from adipose tissue-derived stem cells rescues oocyte quality and infertility in aged mice. Aging (Albany NY) 2017; 9(12):2480.
  32. Court AC, Le‐Gatt A, Luz‐Crawford P, Parra E, Aliaga‐Tobar V, Bátiz LF, et al. Mitochondrial transfer from MSCs to T cells induces Treg differentiation and restricts inflammatory response. EMBO reports 2020; 21(2):e48052.
  33. Abd-Allah SH, Shalaby SM, Pasha HF, Amal S, Raafat N, Shabrawy SM, et al. Mechanistic action of mesenchymal stem cell injection in the treatment of chemically induced ovarian failure in rabbits. Cytotherapy 2013; 15(1):64-75.
  34. Badawy A, Sobh MA, Ahdy M, Abdelhafez MS. Bone marrow mesenchymal stem cell repair of cyclophosphamide-induced ovarian insufficiency in a mouse model. International journal of women's health 2017: 441-7.
  35. Damous LL, Nakamuta JS, Saturi de Carvalho AE, Carvalho KC, Soares-Jr JM, Simoes MD, et al. Does adipose tissue-derived stem cell therapy improve graft quality in freshly grafted ovaries?. Reproductive Biology and Endocrinology 2015; 13(1):1-1.
  36. Terraciano P, Garcez T, Ayres L, Durli I, Baggio M, Kuhl CP, et al. Cell therapy for chemically induced ovarian failure in mice. Stem Cells International 2014; 2014.
  37. Su J, Ding L, Cheng J, Yang J, Li XA, Yan G, et al. Transplantation of adipose-derived stem cells combined with collagen scaffolds restores ovarian function in a rat model of premature ovarian insufficiency. Human Reproduction 2016; 31(5):1075-86.
  38. Abomaray F, Gidlöf S, Bezubik B, Engman M, Götherström C. Mesenchymal stromal cells support endometriotic stromal cells in vitro. Stem cells international 2018; 2018.
  39. Kilic S, Yuksel B, Pinarli F, Albayrak A, Boztok B, Delibasi T. Effect of stem cell application on Asherman syndrome, an experimental rat model. Journal of assisted reproduction and genetics 2014; 31:975-82.
  40. Li J, Mao Q, He J, She H, Zhang Z, Yin C. Human umbilical cord mesenchymal stem cells improve the reserve function of perimenopausal ovary via a paracrine mechanism. Stem cell research & therapy 2017; 8(1):1-1.
  41. Tatone C, Amicarelli F, Carbone MC, Monteleone P, Caserta D, Marci R, et al. Cellular and molecular aspects of ovarian follicle ageing. Human reproduction update 2008; 14(2):131-42.
  42. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989; 246(4935):1306-9.
  43. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983; 219(4587):983-5.
  44. Kosaka N, Sudo N, Miyamoto A, Shimizu T. Vascular endothelial growth factor (VEGF) suppresses ovarian granulosa cell apoptosis in vitro. Biochemical and biophysical research communications 2007; 363(3):733-7.
  45. Gutman G, Barak V, Maslovitz S, Amit A, Lessing JB, Geva E. Regulation of vascular endothelial growth factor-A and its soluble receptor sFlt-1 by luteinizing hormone in vivo: implication for ovarian follicle angiogenesis. Fertility and sterility 2008; 89(4):922-6.
  46. Ito M, Harada T, Tanikawa M, Fujii A, Shiota G, Terakawa N. Hepatocyte growth factor and stem cell factor involvement in paracrine interplays of theca and granulosa cells in the human ovary. Fertility and sterility 2001; 75(5):973-9.
  47. Uzumcu M, Pan Z, Chu Y, Kuhn PE, Zachow R. Immunolocalization of the hepatocyte growth factor (HGF) system in the rat ovary and the anti-apoptotic effect of HGF in rat ovarian granulosa cells in vitro. Reproduction 2006; 132(2):291-9.
  48. Kadakia R, Arraztoa JA, Bondy C, Zhou J. Granulosa cell proliferation is impaired in the Igf1 null ovary. Growth Hormone & IGF Research 2001; 11(4):220-4.
  49. Taketani T, Yamagata Y, Takasaki A, Matsuoka A, Tamura H, Sugino N. Effects of growth hormone and insulin-like growth factor 1 on progesterone production in human luteinized granulosa cells. Fertility and sterility 2008; 90(3):744-8.
  50. Zhou J, Kumar TR, Matzuk MM, Bondy C. Insulin-like growth factor I regulates gonadotropin responsiveness in the murine ovary. Molecular endocrinology 1997; 11(13):1924-33.
  51. Klein NA, Battaglia DE, Miller PB, Branigan EF, Giudice LC, Soules MR. Ovarian follicular development and the follicular fluid hormones and growth factors in normal women of advanced reproductive age. The Journal of Clinical Endocrinology & Metabolism 1996; 81(5):1946-51.
  52. Song D, Zhong Y, Qian C, Zou Q, Ou J, Shi Y, et al. Human umbilical cord mesenchymal stem cells therapy in cyclophosphamide-induced premature ovarian failure rat model. BioMed Research International 2016; 2016.