The effect of 8 weeks of swimming training, cell therapy and vitamin E consumption on testosterone levels and genes involved in the autophagy pathway of infertile male rats

Document Type : Original Article

Authors

1 PhD Student in Sports Physiology, Sari Branch, Islamic Azad University, Sari, Iran.

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

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

4 Assistant Professor, Department of Exercise Physiology, Ghaemshahr Branch, Islamic Azad University, Ghaemshahr, Iran.

10.22038/ijogi.2024.77433.5972

Abstract

Introduction: Infertility is actually a lack of fertility in couples that has not conceived despite a year or more of trying to reproduce. The present study was performed with aim to investigate the effect of 8 weeks of swimming training, cell therapy and vitamin E consumption on testosterone and Lc31 and P62 genes in the testicular tissue of azoospermia model rats.
Methods: In this experimental study, forty 6- to 8-week-old rats were randomly selected, and then the azoospermia model was induced with the busulfan at a dose of 40 mg. After one month, the rats were divided into 8 groups: 1) control, 2) patient, 3) sham, 4) patient + exercise, 5) patient + supplement, 6) patient + cell, 7) patient + supplement + exercise, and 8) patient + cell + exercise. Stem cells were transplanted in the vas deferens at the rate of one million cells for each mouse, they received an oral solution of vitamin E at the rate of 100 mg/kg by gavage, also the training groups performed swimming training continuously with a constant intensity of 60% of the maximum heart rate for 8 weeks, 30 minutes a day, 5 day of the week. Testosterone levels were measured by ELISA and the expression of P62 and LC31 genes in testicular tissue was measured by Real Time PCR technique. Data were analyzed using SPSS statistical software (version 26). P<0.05 was considered statistically significant.
Results: Induction of azoospermia significantly decreased testosterone levels and the expression of Lc31 and P62 genes in testicular tissue compared to the control group (P≤0.05), but showed a significant increase in the supplement, cell, exercise, exercise+supplement and exercise+cell groups compared to the patient and sham groups (P≤0.05).
Conclusion: In the present study, the synergism of swimming exercise with vitamin E and mesenchymal stem cells derived from bone marrow in improving the autophagy flux in experimental rats with azoospermia was observed, which may be effective in increasing testosterone or even fertility.

Keywords

Main Subjects

References

  1. Hashemi Karoii D, Azizi H, Skutella T. Altered G-protein transduction protein gene expression in the testis of infertile patients with nonobstructive azoospermia. DNA and Cell Biology 2023; 42(10):617-37.
  2. Gao F, Li G, Liu C, Gao H, Wang H, Liu W, et al. Autophagy regulates testosterone synthesis by facilitating cholesterol uptake in Leydig cells. Journal of Cell biology 2018; 217(6):2103-19.
  3. Katsuragi Y, Ichimura Y, Komatsu M. p62/SQSTM 1 functions as a signaling hub and an autophagy adaptor. The FEBS journal 2015; 282(24):4672-8.
  4. Anding AL, Baehrecke EH. Cleaning house: selective autophagy of organelles. Developmental cell 2017; 41(1):10-22.
  5. Lv C, Wang X, Guo Y, Yuan S. Role of selective autophagy in spermatogenesis and male fertility. Cells 2020; 9(11):2523.
  6. Gao H, Khawar MB, Li W. Autophagy in reproduction. Autophagy: Biology and Diseases: Basic Science 2019: 453-68.
  7. Stolz A, Ernst A, Dikic I. Cargo recognition and trafficking in selective autophagy. Nature cell biology 2014; 16(6):495-501.
  8. Chow CY, Avila FW, Clark AG, Wolfner MF. Induction of excessive endoplasmic reticulum stress in the Drosophila male accessory gland results in infertility. PloS one 2015; 10(3):e0119386.
  9. Ramalho-Santos J, Varum S, Amaral S, Mota PC, Sousa AP, Amaral A. Mitochondrial functionality in reproduction: from gonads and gametes to embryos and embryonic stem cells. Human reproduction update 2009; 15(5):553-72.
  10. Yang W, Li L, Huang X, Kan G, Lin L, Cheng J, et al. Levels of Leydig cell autophagy regulate the fertility of male naked mole-rats. Oncotarget 2017; 8(58):98677.
  11. Hajizadeh Maleki B, Tartibian B. Combined aerobic and resistance exercise training for improving reproductive function in infertile men: a randomized controlled trial. Applied Physiology, Nutrition, and Metabolism 2017; 42(12):1293-306.
  12. Maleki BH, Tartibian B, Chehrazi M. The effects of three different exercise modalities on markers of male reproduction in healthy subjects: a randomized controlled trial. Reproduction 2017; 153(2):157-74.
  13. Liang J, Zhang H, Zeng Z, Lv J, Huang J, Wu X, et al. MicroRNA profiling of different exercise interventions for alleviating skeletal muscle atrophy in naturally aging rats. Journal of Cachexia, Sarcopenia and Muscle 2023; 14(1):356-68.
  14. Liang J, Zhang H, Zeng Z, Wu L, Zhang Y, Guo Y, et al. Lifelong aerobic exercise alleviates sarcopenia by activating autophagy and inhibiting protein degradation via the AMPK/PGC-1α signaling pathway. Metabolites 2021; 11(5):323.
  15. Ismail HY, Hussein S, Shaker NA, Rizk H, Wally YR. Stem cell treatment trials for regeneration of testicular tissue in laboratory animals. Reproductive Sciences 2023; 30(6):1770-81.
  16. Okada K, Fujisawa M. Recovery of spermatogenesis following cancer treatment with cytotoxic chemotherapy and radiotherapy. The world journal of men's health 2019; 37(2):166.
  17. Tamadon A, Zhan-byrbekuly U, Kairgaliyev I, Khoradmehr A. Mesenchymal stem cell therapy of male infertility. Male Reproductive Health 2019: 105.
  18. Pizato N, Kiffer LF, Luzete BC, Assumpção JA, Correa LH, Braz de Melo HA, et al. Omega 3-DHA and delta-tocotrienol modulate lipid droplet biogenesis and lipophagy in breast cancer cells: The impact in cancer aggressiveness. Nutrients 2019; 11(6):1199.
  19. Shams AA, Vesal S, Hashemi Karoii D, Vesali S, Alizadeh A, Shahhoseini M. Paternal Trans Fatty Acid and Vitamin E Diet Affect the Expression Pattern of Androgen Signaling Pathway Genes in the Testis of Rat Offspring. Paternal Trans Fatty Acid and Vitamin E Diet Affect the Expression Pattern of Androgen Signaling Pathway Genes in the Testis of Rat Offspring, 2023.
  20. Wang M, Li Y, Molenaar A, Li Q, Cao Y, Shen Y, et al. Vitamin E and selenium supplementation synergistically alleviate the injury induced by hydrogen peroxide in bovine granulosa cells. Theriogenology 2021; 170:91-106.
  21. Tamadon A, Mehrabani D, Rahmanifar F, Jahromi AR, Panahi M, Zare S, et al. Induction of spermatogenesis by bone marrow-derived mesenchymal stem cells in busulfan-induced azoospermia in hamster. International journal of stem cells 2015; 8(2):134.
  22. Zohrabi Karani L, Farzanegi P, Azarbayjani MA. The Effect of 8-Weeks of Low-Intensity Swimming Training on Promyelocytic Leukemia Zinc Finger Protein and Spermatid Transition Nuclear Protein Gene Expression in Azoospermic Rats Model. Internal Medicine Today 2020; 26(4):332-47.
  23. Hosseini A, Zare S, Ghaderi Pakdel F, Ahmadi A. Evaluation of the antioxidant effect of ginseng plant extract and vitamin E on the fertility of large male laboratory rats after long-term treatment with cyclophosphamide. Journal of Reproduction and Infertility 2010; 11(4):227-37.
  24. Carter HN, Kim Y, Erlich AT, Zarrin‐khat D, Hood DA. Autophagy and mitophagy flux in young and aged skeletal muscle following chronic contractile activity. The Journal of physiology 2018; 596(16):3567-84.
  25. García-Prat L, Martínez-Vicente M, Perdiguero E, Ortet L, Rodríguez-Ubreva J, Rebollo E, et al. Autophagy maintains stemness by preventing senescence. Nature 2016; 529(7584):37-42.
  26. Vainshtein A, Hood DA. The regulation of autophagy during exercise in skeletal muscle. Journal of Applied Physiology 2016; 120(6):664-73.
  27. Lenhare L, Crisol BM, Silva VR, Katashima CK, Cordeiro AV, Pereira KD, et al. Physical exercise increases Sestrin 2 protein levels and induces autophagy in the skeletal muscle of old mice. Experimental gerontology 2017; 97:17-21.
  28. Kim YA, Kim YS, Oh SL, Kim HJ, Song W. Autophagic response to exercise training in skeletal muscle with age. Journal of physiology and biochemistry 2013; 69:697-705.
  29. Lee Y, Kwon I, Jang Y, Song W, Cosio-Lima LM, Roltsch MH. Potential signaling pathways of acute endurance exercise-induced cardiac autophagy and mitophagy and its possible role in cardioprotection. The journal of physiological sciences 2017; 67:639-54.
  30. Hassan AI, Alam SS. Evaluation of mesenchymal stem cells in treatment of infertility in male rats. Stem cell research & therapy 2014; 5:1-15.
  31. Kobayashi CI, Suda T. Regulation of reactive oxygen species in stem cells and cancer stem cells. Journal of cellular physiology 2012; 227(2):421-30.
  32. Roushandeh AM, Bahadori M, Roudkenar MH. Mesenchymal stem cell-based therapy as a new horizon for kidney injuries. Archives of Medical Research 2017; 48(2):133-46.
  33. Fazeli Z, Abedindo A, Omrani MD, Ghaderian SM. Mesenchymal stem cells (MSCs) therapy for recovery of fertility: a systematic review. Stem cell reviews and reports 2018; 14:1-12.
  34. Lodi D, Iannitti T, Palmieri B. Stem cells in clinical practice: applications and warnings. Journal of Experimental & Clinical Cancer Research 2011; 30:1-20.
  35. Mehrabani D, Hassanshahi MA, Tamadon A, Zare S, Keshavarz S, Rahmanifar F, et al. Adipose tissue-derived mesenchymal stem cells repair germinal cells of seminiferous tubules of busulfan-induced azoospermic rats. Journal of human reproductive sciences 2015; 8(2):103-10.
  36. Park JJ, Lim KH, Baek KH. Annexin-1 regulated by HAUSP is essential for UV-induced damage response. Cell death & disease 2015; 6(2):e1654-.
  37. Monsefi M, Fereydouni B, Rohani L, Talaei T. Mesenchymal stem cells repair germinal cells of seminiferous tubules of sterile rats. Iranian journal of reproductive medicine 2013; 11(7):537.
  38. Bahmyari R, Ariafar A, Sayadi M, Hossieni S, Azima S. The effect of daily intake of selenium, vitamin E and folic acid on sperm parameters in males with idiopathic infertility: a single-blind randomized controlled clinical trial. International Journal of Fertility & Sterility 2021; 15(1):8.
  39. Lee HS. Impact of maternal diet on the epigenome during in utero life and the developmental programming of diseases in childhood and adulthood. Nutrients 2015; 7(11):9492-507.
  40. Al-Attar AM. Antioxidant effect of vitamin E treatment on some heavy metals-induced renal and testicular injuries in male mice. Saudi journal of biological sciences 2011; 18(1):63-72.
The Iranian Journal of Obstetrics, Gynecology and Infertility
Volume 27, Issue 3
May 2024
Pages 37-49

Files

Share

How to cite

Statistics