ISSN: 2423-6241
Continuous Volume
Vol. 7 (2021)
Sitagliptin Suppresses Apoptotic Cell Death and Histological Changes in the Ovaries of Rats with Polycystic Ovary Syndrome
Archives of Medical Laboratory Sciences,
Vol. 7 (2021),
,
Page 1-9 (e22)
https://doi.org/10.22037/amls.v7.34952
Abstract
Background and Aim: Polycystic ovary syndrome (PCOS) is the most typical endocrine disorder affecting reproductive-aged women. The patients with PCOS show decreased follicular granule cells' maturation in their ovaries, probably associated with cell apoptosis. This study was designed to investigate Sitagliptin's protective effect against the apoptotic mechanism in PCOS via evaluating apoptosis rate and the mRNA expressions of apoptotic and anti-apoptotic molecules in PCOS rats.
Methods: PCOS was induced by injection of estradiol valerate (4 mg/kg, I.M.). Twenty-two female rats divided into four groups: Control (n=5), PCOS+Vehicle (n=5), PCOS+ Sitagliptin 25 mg/kg (n=6) and PCOS+ Sitagliptin 50 mg/kg (n=6). Hematoxylin and eosin staining were used to determine qualitative changes in the ovary follicles. The apoptotic index was examined by TUNEL assay, and the quantitative polymerase chain reaction was performed to detect expression levels of Bax and Bcl-2.
Results: Bax mRNA expression was up-regulated (1.38-folds), and Bcl-2 mRNA expression was down-regulated (0.45-folds) in PCOS rats' ovarian tissues. Sitagliptin did not change Bax expression but increased the Bcl-2 mRNA expression (1.95-folds). The apoptosis index was increased in the PCOS group compared with the control group. The number of cystic follicles and pre-antral follicles increased the number of corpus luteum was decreased in PCOS rats compared to control rats. Sitagliptin decreased apoptosis rate and prevented the increase of cystic and pre-antral follicle numbers compared to the PCOS group.
Conclusion: In conclusion, Sitagliptin might have a major role in preventing PCOS development due to its anti-apoptotic properties on PCOS rats' ovaries.
*Corresponding Author: Mohammad Ebrahim Rezvani, Email: me.rezvani@ssu.ac.ir;
ORCID: https://orcid.org/0000-0001-6146-806X
Please cite this article as: Safaeian A, Zare Mehrjerdi F, Yadegari M, Ebrahim Rezvani M. Sitagliptin Suppresses Apoptotic Cell Death and Histological Changes in the Ovaries of Rats with Polycystic Ovary Syndrome. Arch Med Lab Sci. 2021;7:1-9 (e22). https://doi.org/10.22037/amls.v7.34952
- Polycystic Ovary Syndrome
- Apoptosis
- Bcl-2
- Bax
- Sitagliptin
How to Cite
References
Furat Rencber S, Kurnaz Ozbek S, Eraldemır C, Sezer Z, Kum T, Ceylan S, et al. Effect of resveratrol and metformin on ovarian reserve and ultrastructure in PCOS: an experimental study. Journal of Ovarian Research. 2018;11(1):55.
Zhang Y, Hu M, Meng F, Sun X, Xu H, Zhang J, et al. Metformin Ameliorates Uterine Defects in a Rat Model of Polycystic Ovary Syndrome. EBioMedicine. 2017;18:157-70.
Crespo RP, Bachega T, Mendonça BB, Gomes LG. An update of genetic basis of PCOS pathogenesis. Archives of endocrinology and metabolism. 2018;62(3):352-61.
Fu X, He Y, Wang X, Peng D, Chen X, Li X, et al. MicroRNA-16 Promotes Ovarian Granulosa Cell Proliferation and Suppresses Apoptosis Through Targeting PDCD4 in Polycystic Ovarian Syndrome. Cellular Physiology and Biochemistry. 2018;48(2):670-82.
Kriedt KJ, Alchami A, Davies MC. PCOS: diagnosis and management of related infertility. Obstetrics, Gynaecology & Reproductive Medicine. 2019;29(1):1-5.
Franik G, Maksym M, Owczarek AJ, Chudek J, Madej P, Olszanecka-Glinianowicz M. Estradiol/testosterone and estradiol/androstenedione indexes and nutritional status in PCOS women - A pilot study. European journal of obstetrics, gynecology, and reproductive biology. 2019;242:166-9.
Liu C, Peng J, Matzuk MM, Yao HH. Lineage specification of ovarian theca cells requires multicellular interactions via oocyte and granulosa cells. Nature communications. 2015;6:6934.
Bani Mohammad M, Majdi Seghinsara A. Polycystic Ovary Syndrome (PCOS), Diagnostic Criteria, and AMH. Asian Pacific journal of cancer prevention : APJCP. 2017;18(1):17-21.
Wei H, Wang X, Chen K, Ling S, Yi C. Expressional profile of apoptosis and anti-apoptosis proteins in polycystic ovary syndrome patients and related mechanisms. Biomedical Research 2017; 28 (18): 7930-7935.
Salvetti NR, Panzani CG, Gimeno EJ, Neme LG, Alfaro NS, Ortega HH. An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats. Reproductive Biology and Endocrinology. 2009;7(1):68.
Figueroa F, Motta A, Acosta M, Mohamed F, Oliveros L, Forneris M. Role of macrophage secretions on rat polycystic ovary: its effect on apoptosis. REPRODUCTION. 2015;150(5):437-48.
Müller TD, Finan B, Bloom SR, D'Alessio D, Drucker DJ, Flatt PR, et al. Glucagon-like peptide 1 (GLP-1). Molecular metabolism. 2019;30:72-130.
Lee YS, Jun HS. Anti-diabetic actions of glucagon-like peptide-1 on pancreatic beta-cells. Metabolism: clinical and experimental. 2014;63(1):9-19.
Mulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocrine reviews. 2014;35(6):992-1019.
Zheng SL, Roddick AJ, Aghar-Jaffar R, Shun-Shin MJ, Francis D, Oliver N, et al. Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis. Jama. 2018;319(15):1580-91.
Egan AG, Blind E, Dunder K, de Graeff PA, Hummer BT, Bourcier T, et al. Pancreatic safety of incretin-based drugs--FDA and EMA assessment. The New England journal of medicine. 2014;370(9):794-7.
Shi L, Ji Y, Liu D, Liu Y, Xu Y, Cao Y, et al. Sitagliptin attenuates high glucose-induced alterations in migration, proliferation, calcification and apoptosis of vascular smooth muscle cells through ERK1/2 signal pathway. Oncotarget. 2017;8(44):77168-80.
Scott LJ. Sitagliptin: A Review in Type 2 Diabetes. Drugs. 2017;77(2):209-24.
Marcondes FK, Miguel KJ, Melo LL, Spadari-Bratfisch RC. Estrous cycle influences the response of female rats in the elevated plus-maze test. Physiology & behavior. 2001;74(4-5):435-40.
Faheem H, Mansour A, Elkordy A, Rashad S, Shebl M, Madi M, et al. Neuroprotective effects of minocycline and progesterone on white matter injury after focal cerebral ischemia. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2019;64:206-13.
Schulster A, Farookhi R, Brawer JR. Polycystic ovarian condition in estradiol valerate-treated rats: spontaneous changes in characteristic endocrine features. Biology of reproduction. 1984;31(3):587-93.
Brawer JR, Munoz M, Farookhi R. Development of the polycystic ovarian condition (PCO) in the estradiol valerate-treated rat. Biology of reproduction. 1986;35(3):647-55.
Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocrine reviews. 2016;37(5):467-520.
Zhang J, Xu Y, Liu H, Pan Z. MicroRNAs in ovarian follicular atresia and granulosa cell apoptosis. Reproductive Biology and Endocrinology. 2019;17(1):9.
Bas D, Abramovich D, Hernandez F, Tesone M. Altered expression of Bcl-2 and Bax in follicles within dehydroepiandrosterone-induced polycystic ovaries in rats. Cell biology international. 2011;35(5):423-9.
Zheng Q, Li Y, Zhang D, Cui X, Dai K, Yang Y, et al. ANP promotes proliferation and inhibits apoptosis of ovarian granulosa cells by NPRA/PGRMC1/EGFR complex and improves ovary functions of PCOS rats. Cell Death & Disease. 2017;8(10):e3145-e.
Marques C, Mega C, Gonçalves A, Rodrigues-Santos P, Teixeira-Lemos E, Teixeira F, et al. Sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals. Mediators of inflammation. 2014;2014:538737.
- Abstract Viewed: 76 times
- PDF Downloaded: 32 times
