PCOS model: Apoptotic changes and role of vitamin D

Arfa Azhar; Zehra Naseem; Ghulam Haider; Nida Farooqui; Sabah Farhat; Rehana Rehman

doi:10.29333/ejgm/12275

Full Text (PDF)

Arfa Azhar ¹ , Zehra Naseem ¹ , Ghulam Haider ¹ , Nida Farooqui ¹ , Sabah Farhat ¹ , Rehana Rehman ¹ ^*

More Detail

¹ Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, PAKISTAN^* Corresponding Author

Abstract

Aim: This research was aimed to observe apoptotic marker (caspase 3) levels in different groups after treatment with vitamin D in an animal model after inducing polycystic ovary syndrome (PCOS) with dehydroepiandrosterone (DHEA).
Materials and Methods: 30 pre-pubertal female sprague dawley dams were recruited. The animals were distributed 10 each in control, PCOS and vitamin D treated groups. In control group, 0.2 ml of sesame oil was given. PCOS group was administered DHEA by the daily dose of 6 mg/kg for 30 days. In vitamin D treated group, animals were injected 6 mg/ kg/day DHEA daily and 120 ng 1, 25(OH) 2D3/100 g subcutaneously once a week. The occurrence of programmed cell death in PCOS by apoptotic marker (caspase 3) levels.
Results: The results of this study showed significant weight gain, obesity, changes in caspase 3 levels in PCOS group as compared to control and vitamin D treated group.
Conclusion: Administration of vitamin D (120 ng 1, 25(OH) 2D3/100) reduced body weight as well as improved the caspase 3 levels in PCOS induced animals. The results support the effect of vitamin D treatment for metabolic and reproductive characteristic features in PCOS females.

Keywords

animal model
DHEA
polycystic ovary syndrome
vitamin D
caspase 3

License

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Article Type: Original Article

ELECTRON J GEN MED, 2022, Volume 19, Issue 5, Article No: em398

https://doi.org/10.29333/ejgm/12275

Publication date: 26 Jul 2022

Article Views: 816

Article Downloads: 1052

Open Access References How to cite this article

References

Chakraborty P, Goswami SK, Rajani S, et al. Recurrent pregnancy loss in polycystic ovary syndrome: Role of hyperhomocysteinemia and insulin resistance. PLoS One. 2013;8(5):e64446. https://doi.org/10.1371/journal.pone.0064446 PMid:23700477 PMCid:PMC3660299
Kuyucu Y, Celik LS, Kendirlinan O, Tap O, Mete UO. Investigation of the uterine structural changes in the experimental model with polycystic ovary syndrome and effects of vitamin D treatment: An ultrastructural and immunohistochemical study. Reprod Biol. 2018;18(1):53-9. https://doi.org/10.1016/j.repbio.2018.01.002 PMid:29325695
Ding T, Hardiman PJ, Petersen I, Wang F-F, Qu F, Baio G. The prevalence of polycystic ovary syndrome in reproductive-aged women of different ethnicity: A systematic review and meta-analysis. Oncotarget. 2017;8(56):96351. https://doi.org/10.18632/oncotarget.19180 PMid:29221211 PMCid:PMC5707105
Bachelot A. Polycystic ovarian syndrome: Clinical and biological diagnosis. Ann Biol Clin. 2016;74(6):661-7. https://doi.org/10.1684/abc.2016.1184 PMid:27848917
Keane KN, Cruzat VF, Calton EK, et al. Molecular actions of vitamin D in reproductive cell biology. Reprod. 2017;153(1):R29-42. https://doi.org/10.1530/REP-16-0386 PMid:30390417
Lamkanfi M, Kanneganti T-D. Caspase-7: A protease involved in apoptosis and inflammation. Int J Biochem Cell Biol. 2010;42(1):21-4. https://doi.org/10.1016/j.biocel.2009.09.013 PMid:19782763 PMCid:PMC2787741
Nakahara K, Saito H, Saito T, et al. The incidence of apoptotic bodies in membrana granulosa can predict prognosis of ova from patients participating in in vitro fertilization programs. Fertil Steril. 1997;68(2):312-7. https://doi.org/10.1016/S0015-0282(97)81521-X
Palomba S, Piltonen TT, Giudice LC. Endometrial function in women with polycystic ovary syndrome: A comprehensive review. Human Reproduction Update. 2021;27(3):584-618. https://doi.org/10.1093/humupd/dmaa051 PMid:33302299
Aversa A, La Vignera S, Rago R, et al. Fundamental concepts and novel aspects of polycystic ovarian syndrome: Expert consensus resolutions. Front Endocrinol. 2020;11:516. https://doi.org/10.3389/fendo.2020.00516 PMid:32849300 PMCid:PMC7431619
Kuyucu Y, Celik LS, Kendirlinan O, Tap O, Mete UO. Investigation of the uterine structural changes in the experimental model with polycystic ovary syndrome and effects of vitamin D treatment: An ultrastructural and immunohistochemical study. Reprod Biol. 2018;18(1):53-9. https://doi.org/10.1016/j.repbio.2018.01.002 PMid:29325695
Gao L, Cao J-T, Liang Y, et al. Calcitriol attenuates cardiac remodeling and dysfunction in a murine model of polycystic ovary syndrome. Endocr. 2016;52(2):363-73. https://doi.org/10.1007/s12020-015-0797-1 PMid:26578366
Bacopoulou F, Kolias E, Efthymiou V, Antonopoulos CN, Charmandari E. Vitamin D predictors in polycystic ovary syndrome: A meta-analysis. Eur J Clin Invest. 2017;47(10):746-55. https://doi.org/10.1111/eci.12800 PMid:28795765
Dabrowski FA, Grzechocinska B, Wielgos M. The role of vitamin D in reproductive health--a Trojan horse or the Golden Fleece? Nutrients. 2015;7(6):4139-53. https://doi.org/10.3390/nu7064139 PMid:26035242 PMCid:PMC4488777
Kensara OA. Prevalence of hypovitaminosis D, and its association with hypoadiponectinemia and hyperfollistatinemia, in Saudi women with naïve polycystic ovary syndrome. J Clin Transl Endocrinol. 2018;12:20-5. https://doi.org/10.1016/j.jcte.2018.04.001 PMid:29892563 PMCid:PMC5992301
Merhi Z, Doswell A, Krebs K, Cipolla M. Vitamin D alters genes involved in follicular development and steroidogenesis in human cumulus granulosa cells. J Clin Endocr Metab. 2014;99(6):E1137-45. https://doi.org/10.1210/jc.2013-4161 PMid:24628555 PMCid:PMC4037738
Pavlovic M, Berenji K. From rickets prevention to vitamin D intoxication. Eur J Gen Med. 2014;11(3). https://doi.org/10.15197/sabad.1.11.71
Azhar A, Haider G, Naseem Z, Farooqui N, Farooqui MU, Rehman R. Morphological changes in the experimental model of polycystic ovary syndrome and effects of vitamin D treatment. J Obstet Gynaecol Res. 2021;47(3):1164-71. https://doi.org/10.1111/jog.14671 PMid:33496002
Pachiappan S, Ramalingam K, Thenmozhi V. Development of an animal model for polycystic ovarian syndrome in relation to reproductive and metabolic phenotype. J Pharm Sci Res. 2019;11:2827-32.
Liu W, Liu W, Fu Y, Wang Y, Zhang Y. Bak foong pills combined with metformin in the treatment of a polycystic ovarian syndrome rat model. Oncol Lett. 2015;10(3):1819-25. https://doi.org/10.3892/ol.2015.3466 PMid:26622758 PMCid:PMC4533727
Ciepiela P, Duleba AJ, Kowaleczko E, Chelstowski K, Kurzawa R. Vitamin D as a follicular marker of human oocyte quality and a serum marker of in vitro fertilization outcome. J Assist Reprod Genet. 2018;35(7):1265-76. https://doi.org/10.1007/s10815-018-1179-4 PMid:29774457 PMCid:PMC6063829
Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999;6(2):99-104. https://doi.org/10.1038/sj.cdd.4400476 PMid:10200555
Uyanikoglu H, Sabuncu T, Dursun H, Sezen H, Aksoy N. Circulating levels of apoptotic markers and oxidative stress parameters in women with polycystic ovary syndrome: A case-controlled descriptive study. J Biomark. 2017;22(7):643-7. https://doi.org/10.1080/1354750X.2016.1265004 PMid:27899026
Murri M, Luque-Ramírez M, Insenser M, Ojeda-Ojeda M, Escobar-Morreale HF. Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): A systematic review and meta-analysis. Hum Reprod Update. 2013;19(3):268-88. https://doi.org/10.1093/humupd/dms059 PMid:23303572
Hyderali BN, Mala K. Oxidative stress and cardiovascular complications in polycystic ovarian syndrome. Eur J Obstet Gynecol Reprod Biol. 2015;191:15-22. https://doi.org/10.1016/j.ejogrb.2015.05.005 PMid:26066290
Lai Q, Xiang W, Li Q, et al. Oxidative stress in granulosa cells contributes to poor oocyte quality and IVF-ET outcomes in women with polycystic ovary syndrome. Front Med. 2018;12(5):518-24. https://doi.org/10.1007/s11684-017-0575-y PMid:29260383
Nakahara K, Saito H, Saito T, et al. The incidence of apoptotic bodies in membrana granulosa can predict prognosis of ova from patients participating in in vitro fertilization programs. Fertil Steril. 1997;68(2):312-7. https://doi.org/10.1016/S0015-0282(97)81521-X
de Almeida Chuffa LG, Júnior LAL, da Maia Lima AF. Sex steroid receptors and apoptosis-related proteins are differentially expressed in polycystic ovaries of adult dogs. Tissue Cell. 2016;48(1):10-7. https://doi.org/10.1016/j.tice.2015.12.003 PMid:26767421
Gong Y, Luo S, Fan P, Zhu H, Li Y, Huang W. Growth hormone activates PI3K/Akt signaling and inhibits ROS accumulation and apoptosis in granulosa cells of patients with polycystic ovary syndrome. Reprod Biol Endocr. 2020;18(1):1-12. https://doi.org/10.1186/s12958-020-00677-x PMid:33287836 PMCid:PMC7720521
Salehi E, Aflatoonian R, Moeini A, et al. Apoptotic biomarkers in cumulus cells in relation to embryo quality in polycystic ovary syndrome. Arch Gynecol Obstet. 2017;296(6):1219-27. https://doi.org/10.1007/s00404-017-4523-5 PMid:28988321
Zhao K-K, Cui Y-G, Jiang Y-Q, et al. Effect of HSP10 on apoptosis induced by testosterone in cultured mouse ovarian granulosa cells. Eur J Obstet Gynecol Reprod Biol. 2013;171(2):301-6. https://doi.org/10.1016/j.ejogrb.2013.09.026 PMid:24161766
Cai L, Ma X, Liu S, et al. Effects of upregulation of Hsp27 expression on oocyte development and maturation derived from polycystic ovary syndrome. PloS One. 2013;8(12):e83402. https://doi.org/10.1371/journal.pone.0083402 PMid:24391762 PMCid:PMC3877038
Das M, Djahanbakhch O, Hacihanefioglu B, et al. Granulosa cell survival and proliferation are altered in polycystic ovary syndrome. J Clin Endocr Metab. 2008;93(3):881-7. https://doi.org/10.1210/jc.2007-1650 PMid:18073308 PMCid:PMC2679149
Yacobi K, Wojtowicz A, Tsafriri A, Gross A. Gonadotropins enhance caspase-3 and-7 activity and apoptosis in the theca-interstitial cells of rat preovulatory follicles in culture. Endocr. 2004;145(4):1943-51. https://doi.org/10.1210/en.2003-1395 PMid:14726442
Varras M, Polonifi K, Mantzourani M, et al. Expression of antiapoptosis gene survivin in luteinized ovarian granulosa cells of women undergoing IVF or ICSI and embryo transfer: clinical correlations. Reprod Biol Endocr. 2012;10(1):1-10. https://doi.org/10.1186/1477-7827-10-74 PMid:22958786 PMCid:PMC3489854
Altieri DC. Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer. 2008;8(1):61-70. https://doi.org/10.1038/nrc2293 PMid:18075512
Luo G, Yang X, Cheng Y, et al. 25-hydroxyvitamin D3-deficiency enhances oxidative stress and corticosteroid resistance in severe asthma exacerbation. PloS One. 2014;9(11):e111599. https://doi.org/10.1371/journal.pone.0111599 PMid:25380286 PMCid:PMC4224414
Thomson RL, Spedding S, Buckley JD. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clin Endocr. 2012;77(3):343-50. https://doi.org/10.1111/j.1365-2265.2012.04434.x PMid:22574874
Pludowski P, Holick MF, Pilz S, et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality—a review of recent evidence. Autoimmun Rev. 2013;12(10):976-89. https://doi.org/10.1016/j.autrev.2013.02.004 PMid:23542507
Cesur Y, Yuca S, Bektas S, Yilmaz C, Dulger H, Temel H. Vitamin D-dependent rickets: Eight cases. Eur J Gen Med. 2016;13(1):16-20. https://doi.org/10.15197/ejgm.01464
Ozer G. The impact of serum 25-hydroxyvitamin D level on migraine headache. J Clin Exp Invest. 2018;9(1):40-4. https://doi.org/10.5799/jcei.413072
Ozer G. The impact of serum vitamin D concentration on median nerve conduction. J Clin Exp Invest. 2018;9(2):63-6. https://doi.org/10.5799/jcei.433800
Yousefian M, Sadegi SRGP, Sakaki M. Vitamin D supplements’ effect on expediting the weaning process in patients with the stroke. Electron J Gen Med. 2019;16(2):em133. https://doi.org/10.29333/ejgm/94224

How to cite this article

Vancouver

Azhar A, Naseem Z, Haider G, Farooqui N, Farhat S, Rehman R. PCOS model: Apoptotic changes and role of vitamin D. ELECTRON J GEN MED. 2022;19(5):em398. https://doi.org/10.29333/ejgm/12275

APA

Azhar, A., Naseem, Z., Haider, G., Farooqui, N., Farhat, S., & Rehman, R. (2022). PCOS model: Apoptotic changes and role of vitamin D. Electronic Journal of General Medicine, 19(5), em398. https://doi.org/10.29333/ejgm/12275

AMA

Azhar A, Naseem Z, Haider G, Farooqui N, Farhat S, Rehman R. PCOS model: Apoptotic changes and role of vitamin D. ELECTRON J GEN MED. 2022;19(5), em398. https://doi.org/10.29333/ejgm/12275

Chicago

Azhar, Arfa, Zehra Naseem, Ghulam Haider, Nida Farooqui, Sabah Farhat, and Rehana Rehman. "PCOS model: Apoptotic changes and role of vitamin D". Electronic Journal of General Medicine 2022 19 no. 5 (2022): em398. https://doi.org/10.29333/ejgm/12275

Harvard

Azhar, A., Naseem, Z., Haider, G., Farooqui, N., Farhat, S., and Rehman, R. (2022). PCOS model: Apoptotic changes and role of vitamin D. Electronic Journal of General Medicine, 19(5), em398. https://doi.org/10.29333/ejgm/12275

MLA

Azhar, Arfa et al. "PCOS model: Apoptotic changes and role of vitamin D". Electronic Journal of General Medicine, vol. 19, no. 5, 2022, em398. https://doi.org/10.29333/ejgm/12275