197 ORIGINAL ARTICLE Eur J Anat, 25 (2): 197-210 (2021) Infuence of each hesperidin and insulin on diabetes-induced testicular alterations in adult albino rats Maha S. Abd Elsamie, Mona H. Mohammed Ali, Omayma M. Mahmoud, Eman M. Kamel Anatomy Department, Faculty of Medicine, Suez Canal University, Egypt SUMMARY Diabetes mellitus is a chronic metabolic disorder that adversely affects male reproductive organs, resulting in infertility due to testicular atrophy. Hyperglycemia and oxidative stress are considered the main factors implicated in the pathogenesis of diabetic complication. Hesperidin is a natural favonoid with wide pharmacological effects such as hypoglycemic, antioxidant and anti-infammatory. This work aims to study the ability of hesperidin to counteract diabetes-induced testicular alterations. 50 rats were used in this experiment, divided equally and randomly into fve groups: control C, diabetic DM, diabetic +hesperidin DM+H, diabetic +insulin DM+In and hesperidin group H. At the end of the experiment, the rats were sacrifced and evaluated for body weight, blood sugar level, testicular weight, histopathological, immunohistochemistry, morphometric analyses, and spermatozoa analysis. Results revealed that DM signifcantly reduced the body and testicular weights, produced drastic histopathological, morphometric adverse changes of the testicular tissues and morphological abnormalities of the spermatozoa. Hesperidin produced valuable hypoglycemic effect, increased the body and testicular weights, ameliorated the histopathological changes, restored normal germinal epithelium and spermatogenesis, restored morphometric parameters and signifcantly decreased the morphological abnormalities of the spermatozoa caused by DM. Insulin could improve some parameters that were adversely changed by DM, but less than the hesperidin. We conclude that treatment with hesperidin appeared to be more effective in counteracting the toxic effects of diabetes on testes than insulin. Key words: Diabetes – Testis – Hesperidin – Insulin – Albino rats INTRODUCTION Diabetes mellitus is associated with reproductive impairment in both men and women. Its impact on reproduction can be profound, by a decrease in fertility and increase in reproductive failures (Ramalho-Santos et al., 2008). Male reproductive functions can be affected at multiple levels, including increased apoptosis in testicular germ cells, altered spermatogenesis, variation in sperm quality and quantity, decreased testicular weight, and ejaculatory dysfunction and reduced libido (Ricci et al., 2009; Jain and Jangir, 2014). Men with DM have low testosterone levels, associated with decreased luteinizing hormone and follicle- stimulating hormone concentrations. Therefore, diabetes-induced reproductive dysfunction is an important challenge (Ebong et al., 2014). Many articles explained that diabetic complications are due to hyperglycemia and overproduction of reactive oxygen species (ROS) that exceeds natural antioxidant defenses of the body, resulting in cell apoptosis (Ghlissi et al., 2012). Both testicular and sperm cells have increased susceptibility to free radical damage due to higher levels of Corresponding author: Omayma M. Mahmoud. Anatomy Department, Faculty of Medicine, Suez Canal University, Egypt. E-mail: omima34@hotmail.com Submitted: August 16, 2020. Accepted: October 26, 2020