Long-Term Hyperglycemia Impairs Hormonal Balance and Induces Oxidative Damage in Ovaries of Streptozotocin-Induced Diabetic Wistar Rat


Reproductive dysfunction following insulin deficiency in Diabetes Mellitus has been well reported among diabetic patients. However, the mechanism through which Diabetes alters reproductive function remains oblivion. While most studies have focused on diabetes mellitus in male subjects, there have been cases on altered reproductive functions in females. These present study aims to investigate the effect of long term hyperglycemia on diabetic rats’ ovary. Female Wistar rats were assigned into control and diabetic group, each consisting of five animals. The later was induced with STZ (50mg/Kg intraperitoneal injection) and the animals were sacrificed after 14 weeks. The blood glucose, body and organ weight, serum hormone level along with oxidative stress parameters of the ovary and uterus were determined. Histology of the ovary and expression levels of CD79 in the ovary was also assessed. The weight of the diabetic rats after the experiment was significantly lower (p<0.05) than the control. The level of Follicle Stimulating Hormone, Luteinizing hormone and estrogen was significantly lower in the diabetic group. The antioxidant enzymes catalase, superoxide dismutase (SOD) and glutathione-s-transferase (GST) were significantly lower in the diabetic ovary and uterus while the Malondialdehyde (MDA) concentration significantly increased compared to the control group. Histological observation of the ovary showed signs of chronic inflammation and immunohistochemistry for CD79 showed positive expression in the diabetic ovary. Our research findings suggest that Diabetes mellitus alters ovarian health by altering hormonal balance and stimulating oxidative damage

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Allen, D. A., Yaqoob, M. M., & Harwood, S. M. (2005). Mechanisms of high glucose-induced apoptosis and its relationship to diabetic complications. Journal of Nutritional Biochemistry, 16(12), 705–713. https://doi.org/10.1016/j.jnutbio.2005.06.007

Bhargava, P., Kallakury, B. V. S., Ross, J. S., Azumi, N., & Bagg, A. (2007). CD79a is heterogeneously expressed in neoplastic and normal myeloid precursors and megakaryocytes in an antibody clone-dependent manner. American Journal of Clinical Pathology, 128(2), 306–313. https://doi.org/10.1309/UXCDG9PWN7G89Y54

Buege, J. A., & Aust, S. D. (1978). Microsomal lipid peroxidation. Methods in enzymology (Vol. 52, pp. 302–310). Elsevier.

Chatterjee, K., Ali, K. M., De, D., Bera, T. K., Jana, K., Maiti, S., Ghosh, A., & Ghosh, D. (2013). Hyperglycemia-induced alteration in reproductive profile and its amelioration by the polyherbal formulation MTEC (modified) in streptozotocin-induced diabetic albino rats. Biomarkers and Genomic Medicine, 5(1–2), 54–66.

Choudhury, A., & Khole, V. V. (2015). Immune-mediated destruction of ovarian follicles associated with the presence of HSP90 antibodies. Molecular Reproduction and Development, 82(2), 81–89. https://doi.org/10.1002/mrd.22428

Chu, P. G., & Arber, D. A. (2001). CD79 : A Review. 9(2), 97–106.

Claiborne, A. (1985). Catalase activity In Greenwald RA (ed) Handbook of methods for oxygen free radical research. CRC Press, Boca Raton, FL.

Codner, E., Merino, P. M., & Tena-Sempere, M. (2012). Female reproduction and type 1 diabetes: From mechanisms to clinical findings. Human Reproduction Update, 18(5), 568–585. https://doi.org/10.1093/humupd/dms024

Dekel, Y., Glucksam, Y., Elron-Gross, I., & Margalit, R. (2009). Insights into modelling streptozotocin-induced Diabetes in ICR mice. Lab Animal, 38(2), 55–60. https://doi.org/10.1038/laban0209-55

Diamanti-Kandarakis, E., Piperi, C., Patsouris, E., Korkolopoulou, P., Panidis, D., Pawelczyk, L., Papavassiliou, A. G., & Duleba, A. J. (2007). Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries. Histochemistry and Cell Biology, 127(6), 581–589. https://doi.org/10.1007/s00418-006-0265-3

Fedchenko, N., & Reifenrath, J. (2014). Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue - a review. Diagnostic Pathology, 9, 221. https://doi.org/10.1186/s13000-014-0221-9

Garg, D., & Merhi, Z. (2015). Advanced glycation end products: Link between diet and ovulatory dysfunction in PCOS? Nutrients, 7(12), 10129–10144. https://doi.org/10.3390/nu7125524

Habig, W. H., Pabst, M. J., & Jakoby, W. B. (1974). Glutathione S-transferases the first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry, 249(22), 7130–7139.

Hinman, R. M., Smith, M. J., & Cambier, J. C. (2014). B cells and type 1 diabetes... in mice and men. Immunology Letters, 160(2), 128–132. https://doi.org/10.1016/j.imlet.2014.01.010

Komaki, K., Ohno, Y., & Aoki, N. (2005). Gonadal hormones and gonadal function in type 2 diabetes model OLETF (Otsuka Long Evans Tokushima Fatty) rats. Endocrine Journal, 52(3), 345–351. https://doi.org/10.1507/endocrj.52.345

MC Deeds, JM Anderson, AS Armstrong, DA Gastineau, HJ Hiddinga, A Jahangir, NL Eberhardt, and Y. K. (2014). NIH Public Access. Lab Anim., 45(3), 131–140. https://doi.org/10.1258/la.2010.010090.Single

Mistra, H. P., & Fridovich, I. (1972). Superoxide Dismutase: Improved Assay and an Assays Applicable to Acrylamide Gels. J. Biol. Chem.., 247, 1370.

Nandi, A., & Poretsky, L. (2013). Diabetes and the Female Reproductive System. Endocrinology and Metabolism Clinics of North America, 42(4), 915–946.

Norbert W. Tietz Paul R. Finley. (1991). Clinical Guide to Laboratory Tests, Second Edition. International Journal of Gynecological Pathology, 10(1), 105.

Popoola, B., Ashefor, O., Akanni, O., & Adaramoye, O. (2017). Biochemical, Hormonal and Histological Changes in Prostate of Wistar Rats Following Long Term Streptozotocin-induced Diabetes Mellitus. Nigerian Journal of Physiological Sciences : Official Publication of the Physiological Society of Nigeria, 32(1), 75–84.

Qiang Wang and Kelle H. Moley. (2016). HHS Public Access. Physiology & Behavior, 176(1), 139–148.

Randall, R. J., & Lewis, A. (1951). The folin by Oliver. J. Biol. Chem., 193, 265–275.

Shrilatha, B., & Muralidhara. (2007). Occurrence of oxidative impairments, response of antioxidant defences and associated biochemical perturbations in male reproductive milieu in the Streptozotocin-diabetic rat. International Journal of Andrology, 30(6), 508–518. https://doi.org/10.1111/j.1365-2605.2007.00748.x

Steger, R. W., & Rabe, M. B. (1997). The effect of Diabetes mellitus on endocrine and reproductive function. Proceedings of the Society for Experimental Biology and Medicine, 214(1), 1–11. https://doi.org/10.3181/00379727-214-44064

Szkudelski, T. (2001). The Mechanism of Alloxan and Streptozotocin Action in B Cells of the Rat Pancreas. Physiol. Res., 50, 536–546.

Tatewaki, R., Otani, H., Tanaka, O., & Kitada, J. (1989). A morphological study on the reproductive organs as a possible cause of developmental abnormalities in diabetic NOD mice. Histology and Histopathology, 4(3), 343–358.

Tesone, M., Ladenheim, R. G., Oliveira-filho, R. M., Chiauzzi, V. A., Foglia, V. G., & Charreau, E. H. (1983). Ovarian Dysfunction in Streptozotocin-Induced Diabetic Rats. Proceedings of the Society for Experimental Biology and Medicine, 174, 123–130.

Umpierrez, G. E. (2018). Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State. Diabetes Complications, Comorbidities and Related Disorders, Endocrinology, 595–615.

Uotila, M., Ruoslahti, E., & Engvall, E. (1981). Two-site sandwich enzyme immunoassay with monoclonal antibodies to human alpha-fetoprotein. Journal of Immunological Methods, 42(1), 11–15. https://doi.org/10.1016/0022-1759(81)90219-2

Vaskivuo, T. E., & Tapanainen, J. S. (2003). Apoptosis in the human ovary. Reproductive BioMedicine Online, 6(1), 24–35.

Wu, Y., Li, Y., Liao, X., Wang, Z., Li, R., Zou, S., Jiang, T., Zheng, B., Duan, P., & Xiao, J. (2017). Diabetes induces abnormal ovarian function via triggering apoptosis of granulosa cells and suppressing ovarian angiogenesis. International Journal of Biological Sciences, 13(10), 1297–1308. https://doi.org/10.7150/ijbs.21172

Zhao, H., Xu, S., Wang, Z., Li, Y., Guo, W., Lin, C., Gong, S., Li, C., Wang, G., & Cai, L. (2010). Repetitive exposures to low-dose X-rays attenuate testicular apoptotic cell death in streptozotocin-induced diabetes rats. Toxicology Letters, 192(3), 356–364.

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