پاسخ بیان ژن های NR5A1 و CYP19A1 بافت تخمدان رت های مدل تجربی اندومتریوز به فعالیت ورزشی منظم و مکمل آنتی اکسیدانی

نوع مقاله : اصیل پژوهشی

نویسندگان

1 دانشجوی دکتری فیزیولوژی ورزشی، واحد ساری، دانشگاه آزاد اسلامی، ساری، ایران.

2 استاد، گروه فیزیولوژی ورزشی، واحد ساری، دانشگاه آزاد اسلامی، ساری، ایران.

3 استادیار، گروه فیزیولوژی ورزشی، واحد ساری، دانشگاه آزاد اسلامی، ساری، ایران.

4 استادیار، گروه آسیب‌شناسی ورزشی و حرکات اصلاحی، واحد ساری، دانشگاه آزاد اسلامی، ساری، ایران.

10.22038/ijogi.2025.77772.5984

چکیده

مقدمه: شنا می‌تواند با کاهش سطح التهاب و استرس اکسیداتیو به بهبود علائم بیماری اندومتریوز کمک کند. همچنین، ویتامین­ های C و E ممکن است در پاک‌سازی رادیکال ­های آزاد در زنان مبتلا به اندومتریوز دخیل باشند. علاوه بر این، ویتامین‌های B، هم متابولیسم استروژن را به شکل غیرفعال افزایش می­ دهند و هم از تبدیل اسید لینولئیک به گامالینولنیک اسید پشتیبانی می‌کنند. مطالعه حاضر با هدف بررسی اثر تمرین منظم هوازی و ویتامین­ های آنتی‌اکسیدانی بر بیان ژن ­های NR5A1 و CYP19A1 بافت تخمدان رت­ های مدل اندومتریوز انجام شد.
روشکار: در این تحقیق تجربی 50 سر موش صحرایی ماده به 10 گروه: 1- کنترل سالم، 2- اندومتریوز، 3- شم، 4- اندومتریوز + تمرین، 5- اندومتریوز + ویتامین B، 6- اندومتریوز + امگا-3، 7- اندومتریوز + ویتامین E، 8- تمرین+ اندومتریوز+ ویتامین B، 9- تمرین+ اندومتریوز+ ویتامین E و 10- تمرین+ اندومتریوز+ امگا-3 تقسیم شدند. برنامه تمرین شامل 5 روز شنا کردن در هفته و به‌مدت 8 هفته بود. ویتامین E، مکمل امگا-3 و ویتامین B (ترکیبی از ویتامین‌های B6، B2، B1) به شکل گاواژ دریافت شد. بیان ژن CYP19A1و NR5A1 با روش real-time PCR اندازه‌گیری گردید. تجزیه و تحلیل داده‌ها با استفاده از نرم‌افزار آماری SPSS (نسخه 23) و آزمون آنووا در سطح معنی‌داری 05/0 p<انجام شد.
یافته ­ها: القای مدل تجربی اندومتریوز منجر به افزایش معنی­ دار ژن NR5A1 نسبت به گروه کنترل سالم شد (001/0>p). تمرین شنا+ ویتامین E (013/0=p) و تمرین شنا+ امگا-3 (012/0=p) منجر به کاهش معنی­ دار ژن NR5A1 بافت تخمدان در رت­ های مدل تجربی اندومتریوز شد. القای مدل تجربی اندومتریوز نیز منجر به افزایش معنی ­دار ژن CYP19A1 نسبت به گروه کنترل سالم شد (003/0=p). گروه ترکیبی تمرین+ امگا-3 منجر به کاهش معنی‌دار ژن CYP19A1 بافت تخمدان نسبت به گروه اندومتریوز شد (031/0=p).
نتیجه­ گیری: اندومتریوز با افزایش بیان ژن­ های NR5A1 و CYP19A1 بافت تخمدان همراه است و انجام تمرین شنا به همراه مصرف امگا-3 و ویتامین E با کاهش بیان ژن­ های NR5A1 و CYP19A1، به بهبود اندومتریوز کمک خواهد کرد. 

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

Response of NR5A1 and CYP19A1 genes of ovarian tissue in endometriosis experimental model rats to regular exercise and antioxidant supplement

نویسندگان [English]

  • Sakineh Sadeghian 1
  • Parvin Farzanegi 2
  • Amin Farzaneh Hesari 3
  • Yasaman Asadi Saravi 4
1 PhD Student in Exercise Physiology, Sari Branch, Islamic Azad University, Sari, Iran.
2 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 Sport Rehabilitation and Corrective Exercise, Sari Branch, Islamic Azad University, Sari, Iran.
چکیده [English]

Introduction: Swimming can help improve symptoms of endometriosis by reducing inflammation and oxidative stress. Also, vitamins C and E may be involved in scavenging free radicals in women with endometriosis. In addition, vitamins B both increase estrogen metabolism in a passive form and support the conversion of linoleic acid to gamma-linolenic acid. The present study was conducted with aim to investigate the effect of regular aerobic exercise and antioxidant vitamins on the expression of NR5A1 and CYP19A1 genes in ovarian tissue of endometriosis model rats.
Methods: In this experimental study, 50 female rats were divided into 10 groups: 1-healthy control, 2-endometriosis, 3-sham, 4-endometriosis+exercise, 5-endometriosis+vitamin B, 6-endometriosis+omega3, 7-endometriosis+vitaminE, 8-exercise+endometriosis+vitaminB, 9-exercise+endometriosis+vitaminE, 10-exercise+endometriosis+omega3. The training program consisted of swimming 5 days a week for 8 weeks. Vitamin E was administered at a dose of 200mg/kg, omega3 supplement at a dose of 2ml/kg, and vitamin B (a combination of vitamins B6, B2, B1) at a dose of 60 mg/kg per day by gavage. CYP19A1 and NR5A1 gene expression was measured by real-time PCR. Data were analyzed using SPSS software (version 23) and ANOVA test. P<0.05 was considered significant.
Results: The induction of the experimental model of endometriosis caused a significant increase in the NR5A1 gene compared to the healthy control group (p<0.001). Swimming training+vitamin E (p=0.013) and swimming training+omega3 (p=0.012) led to a significant decrease of NR5A1 gene in ovarian tissue in the experimental model of endometriosis rats. The induction of the experimental model of endometriosis also caused a significant increase in the CYP19A1 gene compared to the healthy control group (p=0.003). The combined exercise+omega3 group had a significant decrease in ovarian CYP19A1 gene compared to the endometriosis group (p=0.031).
Conclusion: Endometriosis is associated with increased NR5A1 and CYP19A1 genes in the ovarian tissue and swimming training plus omega3 and vitamin E will help to improve endometriosis by reducing NR5A1 and CYP19A1 gene expression.

کلیدواژه‌ها [English]

  • Antioxidant
  • Endometriosis
  • Exercise
  1. Amini L, Chekini R, Nateghi MR, Haghani H, Jamialahmadi T, Sathyapalan T, et al. The effect of combined vitamin C and vitamin E supplementation on oxidative stress markers in women with endometriosis: a randomized, triple‐blind placebo‐controlled clinical trial. Pain Research and Management 2021; 2021(1):5529741.
  2. Ghasemi SS, Eslamian G, Kazemi SN, Rashidkhani B, Taheripanah R, Nematifard E. Association of dietary intakes and anthropometric indices with endometriosis: a case-control study. The Iranian Journal of Gynecology, Obstetrics and Infertility 2022; 25(2): 79-89.
  3. Augoulea A, Alexandrou A, Creatsa M, Vrachnis N, Lambrinoudaki I. Pathogenesis of endometriosis: the role of genetics, inflammation and oxidative stress. Archives of gynecology and obstetrics 2012; 286:99-103.
  4. Sinha A, Gupta S. The role of antioxidant supplementation in endometriosis therapy. J Gynecol Women’s Health 2017; 3:555601.
  5. Luppino G, Wasniewska M, Coco R, Pepe G, Morabito LA, Li Pomi A, et al. Role of NR5A1 Gene Mutations in Disorders of Sex Development: Molecular and Clinical Features. Current Issues in Molecular Biology 2024; 46(5):4519-32.
  6. Smith OE, Morin F, Roussel V, Bertucci MC, Boyer A, Murphy BD. The role of steroidogenic factor 1 (SF-1) in steroidogenic cell function of the testes and ovaries of mature mice. Reproduction 2023; 165(1):1-7.
  7. Sajinovic T, Baier G. New insights into the diverse functions of the NR2F nuclear orphan receptor family. Frontiers in Bioscience-Landmark 2023; 28(1):13.
  8. Rajakumar A, Senthilkumaran B. Steroidogenesis and its regulation in teleost-a review. Fish Physiology and Biochemistry 2020; 46(3):803-18.
  9. Wu PF, Wang XF, Gao F, Du WG. Role of Cyp19a1 in the female pathway of a freshwater turtle species ( Mauremys reevesii) with temperature-dependent sex determination. Zool Res 2022; 43(1):81-84.
  10. Zondervan KT, Becker CM, Koga K, Missmer SA, Taylor RN, Viganò P. Endometriosis. Nat Rev Dis Primers 2018; 4(1):9.
  11. National Guideline Alliance (UK). Endometriosis: diagnosis and management. London: National Institute for Health and Care Excellence (NICE); 2017.
  12. Aredo JV, Heyrana KJ, Karp BI, Shah JP, Stratton P. Relating chronic pelvic pain and endometriosis to signs of sensitization and myofascial pain and dysfunction. InSeminars in reproductive medicine 2017; 35(01):088-097.
  13. Hansen S, Sverrisdóttir UÁ, Rudnicki M. Impact of exercise on pain perception in women with endometriosis: A systematic review. Acta obstetricia et gynecologica Scandinavica 2021; 100(9):1595-601.
  14. Tennfjord MK, Gabrielsen R, Tellum T. Effect of physical activity and exercise on endometriosis-associated symptoms: a systematic review. BMC women's health 2021; 21:1-10.
  15. Clower L, Fleshman T, Geldenhuys WJ, Santanam N. Targeting oxidative stress involved in endometriosis and its pain. Biomolecules 2022; 12(8):1055.
  16. Xu X, Wu H, Liu Y. Association Between Composite Dietary Antioxidant Index and Endometriosis from NHANES 2001–2006: A Cross-Sectional Study. International Journal of Women's Health 2024: 1845-54.
  17. Ansariniya H, Yavari A, Javaheri A, Zare F. Oxidative stress‐related effects on various aspects of endometriosis. American Journal of Reproductive Immunology 2022; 88(3):e13593.
  18. Bolkar PE, Shelke PA, Sanap GS. Effect of medicinal herbs on dysmenorrheoa. Journal of Pharmacognosy and Phytochemistry 2023; 12(2):150-9.
  19. Jara-Gutiérrez Á, Baladrón V. The role of prostaglandins in different types of cancer. Cells 2021; 10(6):1487.
  20. Santanam N, Kavtaradze N, Murphy A, Dominguez C, Parthasarathy S. Antioxidant supplementation reduces endometriosis-related pelvic pain in humans. Translational Research 2013; 161(3):189-95.
  21. Rezaeei Z, Farzanegi P, Abbaszadeh H. Evaluation of BECLINE-1 and LC3 gene expression in endometriosis rats following regular aerobic exercise and omega-3 intake. Nurse and Physician within War 2022; 10(34):50-7.
  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. Kiani K, Movahedin M, Malekafzali H, Mirfasihi F, Sadati SN, Moini A, et al. Effect of the estrus cycle stage on the establishment of murine endometriosis lesions. International Journal of Reproductive BioMedicine 2018; 16(5):305.
  24. Ghasemian Langharodi S, Farzanegi P, Moradi L. The effect of swimming training and vitamin B6 intake on GATA2 gene expression in endometriosis rat. J Ardabil Univ Med Sci 2019; 19(3):354-65.
  25. Jiao X, Qin Y, Li G, Zhao S, You L, Ma J, et al. Novel NR5A1 missense mutation in premature ovarian failure: detection in han chinese indicates causation in different ethnic groups. PLoS One 2013; 8(9):e74759.
  26. Di Clemente N, Racine C, Pierre A, Taieb J. Anti-Müllerian hormone in female reproduction. Endocrine reviews 2021; 42(6):753-82.
  27. Chand AL, Harrison CA, Shelling AN. Inhibin and premature ovarian failure. Human reproduction update 2010; 16(1):39-50.
  28. Leubolt G, Redondo Monte E, Greif PA. GATA2 mutations in myeloid malignancies: Two zinc fingers in many pies. IUBMB life 2020; 72(1):151-8.
  29. Brandt C, Pedersen BK. The role of exercise‐induced myokines in muscle homeostasis and the defense against chronic diseases. BioMed Research International 2010; 2010(1):520258.
  30. Nimmo MA, Leggate M, Viana JL, King JA. The effect of physical activity on mediators of inflammation. Diabetes, Obesity and Metabolism 2013; 15(s3):51-60.
  31. Rose GL, Skinner TL, Mielke GI, Schaumberg MA. The effect of exercise intensity on chronic inflammation: a systematic review and meta-analysis. Journal of Science and Medicine in Sport 2021; 24(4):345-51.
  32. Krupa A, Padała O, Putowski M, Konopelko M, Piasek E. Available treatment methods for endometriosis. Journal of Education, Health and Sport 2019; 9(7):178-84.
  33. Vitale SG, Capriglione S, Peterlunger I, La Rosa VL, Vitagliano A, Noventa M, et al. The role of oxidative stress and membrane transport systems during endometriosis: a fresh look at a busy corner. Oxidative medicine and cellular longevity 2018; 2018(1):7924021.
  34. Laili AN, Ananingsih I, Wiyasa IW, Indrawan IW, Barlianto W, Yueniwati Y. Protective effect of combined vitamin C and E against ovarian and endometrial toxicity in rats that receiving oral rhodamine B. Biomarkers and Genomic Medicine 2015; 7(4):154-8.
  35. Baboo KD, Chen ZY, Zhang XM. Role of oxidative stress and antioxidant therapies in endometriosis. Reproductive and Developmental Medicine 2019; 3(03):170-6.
  36. Lu X, Wu Z, Wang M, Cheng W. Effects of vitamin C on the outcome of in vitro fertilization–embryo transfer in endometriosis: A randomized controlled study. Journal of International Medical Research 2018; 46(11):4624-33.
  37. Giampaolino P, Corte LD, Foreste V, Bifulco G. Is there a relationship between vitamin D and endometriosis? An overview of the literature. Current pharmaceutical design 2019; 25(22):2421-7.
  38. Tourny C, Zouita A, El Kababi S, Feuillet L, Saeidi A, Laher I, et al. Endometriosis and physical activity: a narrative review. International Journal of Gynecology & Obstetrics 2023; 163(3):747-56.