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Investigation of protective effects of dehydroepiandrosterone (DHEA) against toxic damage caused by doxorubicin in rat ovaries

Year 2020, , 406 - 413, 20.10.2020
https://doi.org/10.18521/ktd.680703

Abstract

Objective: Our aim is to evaluate whether dehydroepiandrosterone has a protective effect on doxorubicin-induced ovarian damage.
Methods: The rats were divided into three groups. Group 1 (the control Group): no treatment was administered. Intact ovarian tissue was removed, and blood samples were taken for the anti-Mullerian hormone (AMH) test. Group 2 (the doxorubicin Group): Rats received doxorubicin intraperitoneally at a single dose of 3 mg/kg. Group 3 (the doxorubicin + DHEA Group): Rats received doxorubicin intraperitoneally at a single dose of 3 mg/kg at baseline and DHEA subcutaneously for 10 days at a dose of 60 mg/kg daily. Rats in groups 2 and 3 were sacrificed at the end of 10 days, ovarian tissues were removed and blood samples were taken for AMH test.
Results: While normal ovarian tissue damage scores were zero except hemorrhage, doxorubicin showed significant damage and histopathological changes in all rats. Doxorubicin and Doxorubicin + DHEA groups had higher edema, vascular congestion, cellular degeneration, and total damage scores than the normal ovarian group. The number of antral follicles and ovarian volume decreased in the doxorubicin group compared to the normal ovarian group (p = 0.011 and 0.002, respectively). In the doxorubicin + DHEA group, ovarian volume was similar to the normal ovary (p = 0.091), but the number of antral follicles was significantly lower in this group (p = 0.002). AMH values did not differ between the normal ovarian group and the other groups.
Conclusions: It was concluded that DHEA was not effective in preventing ovarian damage caused by doxorubicin.

References

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Patient-reported outcomes in the evaluation of toxicity of anticancer treatments. Nature reviews Clinical oncology. 2016;13(5):319-25. 7. Liu Y, Li K, Wu Y, Ma J, Tang P, Liu Y, et al. PVA reinforced gossypolone and doxorubicin pi-pi stacking nanoparticles towards tumor targeting and ultralow dose synergistic chemotherapy. Biomaterials science. 2019;7(9):3662-74. 8. Iguchi N, Donmez MI, Carrasco A, Jr., Wilcox DT. Doxorubicin induces detrusor smooth muscle impairments through myosin dysregulation, leading to a risk of lower urinary tract dysfunction. 2019;317(1):F197-f206. 9. Blum RH, Carter SK. Adriamycin. A new anticancer drug with significant clinical activity. Annals of internal medicine. 1974;80(2):249-59. 10. Vejpongsa P, Yeh ET. Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities. Journal of the American College of Cardiology. 2014;64(9):938-45. 11. Vendramini V, Sasso-Cerri E, Miraglia SM. Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status. Reproductive biology and endocrinology : RB&E. 2010;8:3. 12. Hopkins-Donaldson S, Yan P, Bourloud KB, Muhlethaler A, Bodmer JL, Gross N. Doxorubicin-induced death in neuroblastoma does not involve death receptors in S-type cells and is caspase-independent in N-type cells. Oncogene. 2002;21(39):6132-7. 13. Pandey S, Kuo WW, Shen CY, Yeh YL, Ho TJ, Chen RJ, et al. Insulin-like growth factor II receptor-alpha is a novel stress-inducible contributor to cardiac damage underpinning doxorubicin-induced oxidative stress and perturbed mitochondrial autophagy. American journal of physiology Cell physiology. 2019;317(2):C235-c43. 14. Koleini N, Nickel BE, Edel AL, Fandrich RR, Ravandi A, Kardami E. Oxidized phospholipids in Doxorubicin-induced cardiotoxicity. Chemico-biological interactions. 2019;303:35-9. 15. Yu J, Wang C, Kong Q, Wu X, Lu JJ, Chen X. Recent progress in doxorubicin-induced cardiotoxicity and protective potential of natural products. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2018;40:125-39. 16. Kuzu M, Yildirim S, Kandemir FM, Kucukler S, Caglayan C, Turk E, et al. Protective effect of morin on doxorubicin-induced hepatorenal toxicity in rats. Chemico-biological interactions. 2019;308:89-100. 17. Morgan S, Anderson RA, Gourley C, Wallace WH, Spears N. How do chemotherapeutic agents damage the ovary? Human reproduction update. 2012;18(5):525-35. 18. Damodar G, Smitha T, Gopinath S, Vijayakumar S, Rao Y. An evaluation of hepatotoxicity in breast cancer patients receiving injection Doxorubicin. Annals of medical and health sciences research. 2014;4(1):74-9. 19. Hofland KF, Thougaard AV, Sehested M, Jensen PB. Dexrazoxane protects against myelosuppression from the DNA cleavage-enhancing drugs etoposide and daunorubicin but not doxorubicin. Clinical cancer research : an official journal of the American Association for Cancer Research. 2005;11(10):3915-24. 20. Zhang S, Liu X, Bawa-Khalfe T, Lu LS, Lyu YL, Liu LF, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nature medicine. 2012;18(11):1639-42. 21. Jayaprakasan K, Narkwichean A, Maalouf WE, Campbell BK. Efficacy of dehydroepiandrosterone to overcome the effect of ovarian ageing (DITTO): a proof of principle randomised controlled trial protocol. BMJ open. 2014;4(10):e005767. 22. Klinge CM, Clark BJ, Prough RA. Dehydroepiandrosterone Research: Past, Current, and Future. Vitamins and hormones. 2018;108:1-28. 23. Mostajeran F, Tehrani H, Ghoreishi E. Effects of Dehydroepiandrosterone on In Vitro Fertilization Among Women Aging Over 35 Years and Normal Ovarian Reserve. Journal of family & reproductive health. 2018;12(3):129-33. 24. Casson PR, Lindsay MS, Pisarska MD, Carson SA, Buster JE. Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Human reproduction. 2000;15(10):2129-32. 25. Weissman A, Horowitz E, Ravhon A, Golan A, Levran D. Dehydroepiandrosterone supplementation increases baseline follicular phase progesterone levels. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2011;27(12):1014-7. 26. Mahmoud YI, Mahmoud AA, Abo-Zeid FS, Fares NH. Effects of dehydroepiandrosterone on the ovarian reserve and pregnancy outcomes in perimenopausal rats (DHEA and fertility in perimenopausal rats). Life sciences. 2018;199:131-8. 27. Nishi K, Gunasekaran VP, Arunachalam J, Ganeshan M. Doxorubicin-induced female reproductive toxicity: an assessment of ovarian follicular apoptosis, cyclicity and reproductive tissue histology in Wistar rats. Drug and chemical toxicology. 2018;41(1):72-81. 28. Hassa H, Aydin Y, Ozatik O, Erol K, Ozatik Y. Effects of dehydroepiandrosterone (DHEA) on follicular dynamics in a diminished ovarian reserve in vivo model. Systems biology in reproductive medicine. 2015;61(3):117-21. 29. Wang YX, Zhu WJ, Xie BG. Expression of PPAR-gamma in adipose tissue of rats with polycystic ovary syndrome induced by DHEA. Molecular medicine reports. 2014;9(3):889-93. 30. Celik O, Turkoz Y, Hascalik S, Hascalik M, Cigremis Y, Mizrak B, et al. The protective effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in rat ovary. European journal of obstetrics, gynecology, and reproductive biology. 2004;117(2):183-8. 31. Parlakgumus HA, Aka Bolat F, Bulgan Kilicdag E, Simsek E, Parlakgumus A. Atorvastatin for ovarian torsion: effects on follicle counts, AMH, and VEGF expression. European journal of obstetrics, gynecology, and reproductive biology. 2014;175:186-90. 32. Ben-Aharon I, Bar-Joseph H, Tzarfaty G, Kuchinsky L, Rizel S, Stemmer SM, et al. Doxorubicin-induced ovarian toxicity. Reproductive biology and endocrinology : RB&E. 2010;8:20. 33. Marcello MF, Nuciforo G, Romeo R, Di Dino G, Russo I, Russo A, et al. Structural and ultrastructural study of the ovary in childhood leukemia after successful treatment. Cancer. 1990;66(10):2099-104. 34. Zhou S, Palmeira CM, Wallace KB. Doxorubicin-induced persistent oxidative stress to cardiac myocytes. Toxicology letters. 2001;121(3):151-7. 35. Zhao X, Jin Y, Li L, Xu L, Tang Z, Qi Y, et al. MicroRNA-128-3p aggravates doxorubicin-induced liver injury by promoting oxidative stress via targeting Sirtuin-1. Pharmacological research. 2019;146:104276. 36. MadanKumar P, NaveenKumar P, Devaraj H, NiranjaliDevaraj S. Morin, a dietary flavonoid, exhibits anti-fibrotic effect and induces apoptosis of activated hepatic stellate cells by suppressing canonical NF-kappaB signaling. Biochimie. 2015;110:107-18. 37. Xiao S, Zhang J, Liu M, Iwahata H, Rogers HB, Woodruff TK. Doxorubicin Has Dose-Dependent Toxicity on Mouse Ovarian Follicle Development, Hormone Secretion, and Oocyte Maturation. Toxicological sciences : an official journal of the Society of Toxicology. 2017;157(2):320-9. 38. Yeung TW, Chai J, Li RH, Lee VC, Ho PC, Ng EH. A randomized, controlled, pilot trial on the effect of dehydroepiandrosterone on ovarian response markers, ovarian response, and in vitro fertilization outcomes in poor responders. Fertility and sterility. 2014;102(1):108-15.e1. 39. Mo Q, Lu SF, Simon NG. Dehydroepiandrosterone and its metabolites: differential effects on androgen receptor trafficking and transcriptional activity. The Journal of steroid biochemistry and molecular biology. 2006;99(1):50-8. 40. Chimote BN, Chimote NM. Dehydroepiandrosterone (DHEA) and Its Sulfate (DHEA-S) in Mammalian Reproduction: Known Roles and Novel Paradigms. Vitamins and hormones. 2018;108:223-50. 41. Broer SL, Dolleman M, Opmeer BC, Fauser BC, Mol BW, Broekmans FJ. AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis. Human reproduction update. 2011;17(1):46-54. 42. Iliodromiti S, Nelson SM. Ovarian response biomarkers: physiology and performance. Current opinion in obstetrics & gynecology. 2015;27(3):182-6. 43. Stracquadanio M, Ciotta L, Palumbo MA. Relationship between serum anti-Mullerian hormone and intrafollicular AMH levels in PCOS women. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2018;34(3):223-8. 44. Skinner MK. Regulation of primordial follicle assembly and development. Human reproduction update. 2005;11(5):461-71. 45. Pawelczak M, Kenigsberg L, Milla S, Liu YH, Shah B. Elevated serum anti-Mullerian hormone in adolescents with polycystic ovary syndrome: relationship to ultrasound features. Journal of pediatric endocrinology & metabolism : JPEM. 2012;25(9-10):983-9.

Investigation of Protective Effects of Dehydroepiandrosterone (DHEA) Against Toxic Damage Caused by Doxorubicin in Rat Ovaries

Year 2020, , 406 - 413, 20.10.2020
https://doi.org/10.18521/ktd.680703

Abstract

Amaç : Amacımız, dehidroepiandrosteronun (DHEA) doksorubisine bağlı over hasarı üzerinde koruyucu bir etkisi olup olmadığını değerlendirmektir.

Metod: Ratlar üç gruba ayrıldı. Grup 1 (kontrol grubu) tedavi uygulanmadı. Sağlam over dokusu çıkarıldı ve Anti-Mulleran Hormon (AMH) testi için kan örnekleri alındı. Grup 2 (doksorubisin grubu), ratlara 3 mg/kg'lık tek bir dozda intraperitonal yoldan doksorubisin verildi. Grup 3 (doksorubisin + DHEA grubu), ratlara intraperitonal yolla 3 mg/kg'lık tek bir dozda ve günde 60 mg / kg'lık bir dozda subcutan DHEA'ya ilaveten tek doz doz doksorubisin verildi. Grup 2 ve 3'teki ratların onuncu günün sonunda yumurtalık dokuları alındı ve AMH testi için kan örnekleri alındı.

Bulgular: Normal over doku hasarı skorları kanama dışında sıfır olmakla birlikte, doksorubisin tüm deneklerde anlamlı hasar ve histopatolojik değişiklikler gösterdi. Doksorubisin ve Doksorubisin + DHEA gruplarında normal over grubundan daha yüksek ödem, vasküler konjesyon, hücresel dejenerasyon ve toplam hasar skorları vardı. Antral folikül sayısı ve yumurtalık hacmi doksorubisin grubunda normal over grubuna göre azaldı (sırasıyla p = 0.011 ve 0.002). Doksorubisin + DHEA grubundaki over hacmi, normal over hacmine benzerdi (p = 0.091), ancak antral folikül sayısı bu grupta anlamlı olarak daha düşüktü (p = 0.002). AMH değerleri normal over grubu ile diğer gruplar arasında farklılık göstermedi.

Sonuç : DHEA'nın doksorubisinin neden olduğu over hasarını önlemede etkili olmadığı sonucuna varıldı.

References

  • 1. Niringiyumukiza JD, Cai H, Chen L, Li Y, Wang L, Zhang M, et al. Protective properties of glycogen synthase kinase-3 inhibition against doxorubicin-induced oxidative damage to mouse ovarian reserve. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2019;116:108963. 2. Roti Roti EC, Ringelstetter AK, Kropp J, Abbott DH, Salih SM. Bortezomib prevents acute doxorubicin ovarian insult and follicle demise, improving the fertility window and pup birth weight in mice. PloS one. 2014;9(9):e108174. 3. Gansler T, Ganz PA, Grant M, Greene FL, Johnstone P, Mahoney M, et al. Sixty years of CA: a cancer journal for clinicians. CA: a cancer journal for clinicians. 2010;60(6):345-50. 4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: a cancer journal for clinicians. 2016;66(1):7-30. 5. Siegel RL, Miller KD. Cancer statistics, 2019. 2019;69(1):7-34. 6. Di Maio M, Basch E, Bryce J, Perrone F. Patient-reported outcomes in the evaluation of toxicity of anticancer treatments. Nature reviews Clinical oncology. 2016;13(5):319-25. 7. Liu Y, Li K, Wu Y, Ma J, Tang P, Liu Y, et al. PVA reinforced gossypolone and doxorubicin pi-pi stacking nanoparticles towards tumor targeting and ultralow dose synergistic chemotherapy. Biomaterials science. 2019;7(9):3662-74. 8. Iguchi N, Donmez MI, Carrasco A, Jr., Wilcox DT. Doxorubicin induces detrusor smooth muscle impairments through myosin dysregulation, leading to a risk of lower urinary tract dysfunction. 2019;317(1):F197-f206. 9. Blum RH, Carter SK. Adriamycin. A new anticancer drug with significant clinical activity. Annals of internal medicine. 1974;80(2):249-59. 10. Vejpongsa P, Yeh ET. Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities. Journal of the American College of Cardiology. 2014;64(9):938-45. 11. Vendramini V, Sasso-Cerri E, Miraglia SM. Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status. Reproductive biology and endocrinology : RB&E. 2010;8:3. 12. Hopkins-Donaldson S, Yan P, Bourloud KB, Muhlethaler A, Bodmer JL, Gross N. Doxorubicin-induced death in neuroblastoma does not involve death receptors in S-type cells and is caspase-independent in N-type cells. Oncogene. 2002;21(39):6132-7. 13. Pandey S, Kuo WW, Shen CY, Yeh YL, Ho TJ, Chen RJ, et al. Insulin-like growth factor II receptor-alpha is a novel stress-inducible contributor to cardiac damage underpinning doxorubicin-induced oxidative stress and perturbed mitochondrial autophagy. American journal of physiology Cell physiology. 2019;317(2):C235-c43. 14. Koleini N, Nickel BE, Edel AL, Fandrich RR, Ravandi A, Kardami E. Oxidized phospholipids in Doxorubicin-induced cardiotoxicity. Chemico-biological interactions. 2019;303:35-9. 15. Yu J, Wang C, Kong Q, Wu X, Lu JJ, Chen X. Recent progress in doxorubicin-induced cardiotoxicity and protective potential of natural products. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2018;40:125-39. 16. Kuzu M, Yildirim S, Kandemir FM, Kucukler S, Caglayan C, Turk E, et al. Protective effect of morin on doxorubicin-induced hepatorenal toxicity in rats. Chemico-biological interactions. 2019;308:89-100. 17. Morgan S, Anderson RA, Gourley C, Wallace WH, Spears N. How do chemotherapeutic agents damage the ovary? Human reproduction update. 2012;18(5):525-35. 18. Damodar G, Smitha T, Gopinath S, Vijayakumar S, Rao Y. An evaluation of hepatotoxicity in breast cancer patients receiving injection Doxorubicin. Annals of medical and health sciences research. 2014;4(1):74-9. 19. Hofland KF, Thougaard AV, Sehested M, Jensen PB. Dexrazoxane protects against myelosuppression from the DNA cleavage-enhancing drugs etoposide and daunorubicin but not doxorubicin. Clinical cancer research : an official journal of the American Association for Cancer Research. 2005;11(10):3915-24. 20. Zhang S, Liu X, Bawa-Khalfe T, Lu LS, Lyu YL, Liu LF, et al. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nature medicine. 2012;18(11):1639-42. 21. Jayaprakasan K, Narkwichean A, Maalouf WE, Campbell BK. Efficacy of dehydroepiandrosterone to overcome the effect of ovarian ageing (DITTO): a proof of principle randomised controlled trial protocol. BMJ open. 2014;4(10):e005767. 22. Klinge CM, Clark BJ, Prough RA. Dehydroepiandrosterone Research: Past, Current, and Future. Vitamins and hormones. 2018;108:1-28. 23. Mostajeran F, Tehrani H, Ghoreishi E. Effects of Dehydroepiandrosterone on In Vitro Fertilization Among Women Aging Over 35 Years and Normal Ovarian Reserve. Journal of family & reproductive health. 2018;12(3):129-33. 24. Casson PR, Lindsay MS, Pisarska MD, Carson SA, Buster JE. Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Human reproduction. 2000;15(10):2129-32. 25. Weissman A, Horowitz E, Ravhon A, Golan A, Levran D. Dehydroepiandrosterone supplementation increases baseline follicular phase progesterone levels. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2011;27(12):1014-7. 26. Mahmoud YI, Mahmoud AA, Abo-Zeid FS, Fares NH. Effects of dehydroepiandrosterone on the ovarian reserve and pregnancy outcomes in perimenopausal rats (DHEA and fertility in perimenopausal rats). Life sciences. 2018;199:131-8. 27. Nishi K, Gunasekaran VP, Arunachalam J, Ganeshan M. Doxorubicin-induced female reproductive toxicity: an assessment of ovarian follicular apoptosis, cyclicity and reproductive tissue histology in Wistar rats. Drug and chemical toxicology. 2018;41(1):72-81. 28. Hassa H, Aydin Y, Ozatik O, Erol K, Ozatik Y. Effects of dehydroepiandrosterone (DHEA) on follicular dynamics in a diminished ovarian reserve in vivo model. Systems biology in reproductive medicine. 2015;61(3):117-21. 29. Wang YX, Zhu WJ, Xie BG. Expression of PPAR-gamma in adipose tissue of rats with polycystic ovary syndrome induced by DHEA. Molecular medicine reports. 2014;9(3):889-93. 30. Celik O, Turkoz Y, Hascalik S, Hascalik M, Cigremis Y, Mizrak B, et al. The protective effect of caffeic acid phenethyl ester on ischemia-reperfusion injury in rat ovary. European journal of obstetrics, gynecology, and reproductive biology. 2004;117(2):183-8. 31. Parlakgumus HA, Aka Bolat F, Bulgan Kilicdag E, Simsek E, Parlakgumus A. Atorvastatin for ovarian torsion: effects on follicle counts, AMH, and VEGF expression. European journal of obstetrics, gynecology, and reproductive biology. 2014;175:186-90. 32. Ben-Aharon I, Bar-Joseph H, Tzarfaty G, Kuchinsky L, Rizel S, Stemmer SM, et al. Doxorubicin-induced ovarian toxicity. Reproductive biology and endocrinology : RB&E. 2010;8:20. 33. Marcello MF, Nuciforo G, Romeo R, Di Dino G, Russo I, Russo A, et al. Structural and ultrastructural study of the ovary in childhood leukemia after successful treatment. Cancer. 1990;66(10):2099-104. 34. Zhou S, Palmeira CM, Wallace KB. Doxorubicin-induced persistent oxidative stress to cardiac myocytes. Toxicology letters. 2001;121(3):151-7. 35. Zhao X, Jin Y, Li L, Xu L, Tang Z, Qi Y, et al. MicroRNA-128-3p aggravates doxorubicin-induced liver injury by promoting oxidative stress via targeting Sirtuin-1. Pharmacological research. 2019;146:104276. 36. MadanKumar P, NaveenKumar P, Devaraj H, NiranjaliDevaraj S. Morin, a dietary flavonoid, exhibits anti-fibrotic effect and induces apoptosis of activated hepatic stellate cells by suppressing canonical NF-kappaB signaling. Biochimie. 2015;110:107-18. 37. Xiao S, Zhang J, Liu M, Iwahata H, Rogers HB, Woodruff TK. Doxorubicin Has Dose-Dependent Toxicity on Mouse Ovarian Follicle Development, Hormone Secretion, and Oocyte Maturation. Toxicological sciences : an official journal of the Society of Toxicology. 2017;157(2):320-9. 38. Yeung TW, Chai J, Li RH, Lee VC, Ho PC, Ng EH. A randomized, controlled, pilot trial on the effect of dehydroepiandrosterone on ovarian response markers, ovarian response, and in vitro fertilization outcomes in poor responders. Fertility and sterility. 2014;102(1):108-15.e1. 39. Mo Q, Lu SF, Simon NG. Dehydroepiandrosterone and its metabolites: differential effects on androgen receptor trafficking and transcriptional activity. The Journal of steroid biochemistry and molecular biology. 2006;99(1):50-8. 40. Chimote BN, Chimote NM. Dehydroepiandrosterone (DHEA) and Its Sulfate (DHEA-S) in Mammalian Reproduction: Known Roles and Novel Paradigms. Vitamins and hormones. 2018;108:223-50. 41. Broer SL, Dolleman M, Opmeer BC, Fauser BC, Mol BW, Broekmans FJ. AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis. Human reproduction update. 2011;17(1):46-54. 42. Iliodromiti S, Nelson SM. Ovarian response biomarkers: physiology and performance. Current opinion in obstetrics & gynecology. 2015;27(3):182-6. 43. Stracquadanio M, Ciotta L, Palumbo MA. Relationship between serum anti-Mullerian hormone and intrafollicular AMH levels in PCOS women. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2018;34(3):223-8. 44. Skinner MK. Regulation of primordial follicle assembly and development. Human reproduction update. 2005;11(5):461-71. 45. Pawelczak M, Kenigsberg L, Milla S, Liu YH, Shah B. Elevated serum anti-Mullerian hormone in adolescents with polycystic ovary syndrome: relationship to ultrasound features. Journal of pediatric endocrinology & metabolism : JPEM. 2012;25(9-10):983-9.
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Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

Önder Sakin 0000-0001-6036-9975

Muhammet Ali Oruç 0000-0001-8862-5328

Yasemin Alan 0000-0003-2680-814X

Ali Doğukan Anğın 0000-0003-1954-8546

Kayhan Başak 0000-0003-1960-8924

Publication Date October 20, 2020
Acceptance Date September 5, 2020
Published in Issue Year 2020

Cite

APA Sakin, Ö., Oruç, M. A., Alan, Y., Anğın, A. D., et al. (2020). Investigation of protective effects of dehydroepiandrosterone (DHEA) against toxic damage caused by doxorubicin in rat ovaries. Konuralp Medical Journal, 12(3), 406-413. https://doi.org/10.18521/ktd.680703
AMA Sakin Ö, Oruç MA, Alan Y, Anğın AD, Başak K. Investigation of protective effects of dehydroepiandrosterone (DHEA) against toxic damage caused by doxorubicin in rat ovaries. Konuralp Medical Journal. October 2020;12(3):406-413. doi:10.18521/ktd.680703
Chicago Sakin, Önder, Muhammet Ali Oruç, Yasemin Alan, Ali Doğukan Anğın, and Kayhan Başak. “Investigation of Protective Effects of Dehydroepiandrosterone (DHEA) Against Toxic Damage Caused by Doxorubicin in Rat Ovaries”. Konuralp Medical Journal 12, no. 3 (October 2020): 406-13. https://doi.org/10.18521/ktd.680703.
EndNote Sakin Ö, Oruç MA, Alan Y, Anğın AD, Başak K (October 1, 2020) Investigation of protective effects of dehydroepiandrosterone (DHEA) against toxic damage caused by doxorubicin in rat ovaries. Konuralp Medical Journal 12 3 406–413.
IEEE Ö. Sakin, M. A. Oruç, Y. Alan, A. D. Anğın, and K. Başak, “Investigation of protective effects of dehydroepiandrosterone (DHEA) against toxic damage caused by doxorubicin in rat ovaries”, Konuralp Medical Journal, vol. 12, no. 3, pp. 406–413, 2020, doi: 10.18521/ktd.680703.
ISNAD Sakin, Önder et al. “Investigation of Protective Effects of Dehydroepiandrosterone (DHEA) Against Toxic Damage Caused by Doxorubicin in Rat Ovaries”. Konuralp Medical Journal 12/3 (October 2020), 406-413. https://doi.org/10.18521/ktd.680703.
JAMA Sakin Ö, Oruç MA, Alan Y, Anğın AD, Başak K. Investigation of protective effects of dehydroepiandrosterone (DHEA) against toxic damage caused by doxorubicin in rat ovaries. Konuralp Medical Journal. 2020;12:406–413.
MLA Sakin, Önder et al. “Investigation of Protective Effects of Dehydroepiandrosterone (DHEA) Against Toxic Damage Caused by Doxorubicin in Rat Ovaries”. Konuralp Medical Journal, vol. 12, no. 3, 2020, pp. 406-13, doi:10.18521/ktd.680703.
Vancouver Sakin Ö, Oruç MA, Alan Y, Anğın AD, Başak K. Investigation of protective effects of dehydroepiandrosterone (DHEA) against toxic damage caused by doxorubicin in rat ovaries. Konuralp Medical Journal. 2020;12(3):406-13.