Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet

Abstract

Purpose The study aims to elucidate the changes in testicular spermatogenic function in high-fat diet (HFD)-induced obese rats and to evaluate the protective effects of metformin intervention. Methods Male Sprague-Dawley rats (n=18) were randomly divided into a control group (standard diet), an HFD group, and a metformin group (HFD + metformin at 100 mg/kg, once daily by oral gavage). After 8 weeks, rats were euthanized, and the weights of body and testes were measured. Testis and epididymis were dissected and hematoxylin-eosin-stained for histopathological examination and semen parameter analysis. Blood samples were collected for assessment of sex hormones and metabolic parameters (serum glucose, insulin, and leptin). Spermatogenic cell apoptosis was accessed by TUNEL. Results Compared with the control group, the final body weight and weight gain were significantly higher in HFD rats, while the testicle weight and coefficients were lower. In HFD rats, metformin treatment induced weight loss and increased testicle weight (P<0.05). In HFD rats, obvious pathological changes in the testicular tissue were characterized by small, atrophic, and distorted seminiferous tubules and destroyed basement membrane. Metformin treatment protected against the HFD-induced decrease in the number of spermatogonia, Sertoli cells, and Leydig cells (P<0.05); ameliorated the HFD-induced increases in serum glucose, insulin, leptin, and estrogen; and decreased serum testosterone (P<0.05) and reduced the rate of testicular cell apoptosis in obese male rats. Finally, metformin significantly improved semen parameters (including concentration, viability, motility, and normal morphology) in HFD rats (P<0.05). Conclusions HFD-induced obesity in rats results in detrimental effects on spermatogenesis, semen quality, endogenous hormones, and testicular cell apoptosis. Metformin intervention improved the semen parameters, possibly due to its effects on weight loss, increased testicular weight, reduced testicular cell apoptosis, and resulted in restoration of hormonal homeostasis and correction of metabolic disorder.

Protective Effects of Fluvastatin on Reproductive Function in Obese Male Rats Induced by High-Fat Diet through Enhanced Signaling of mTOR

“…This was supported by the reduction in the testicular weight and coefficient in the HFD group compared with the control group, which was consistent with the Yan et al's findings [33]. Furthermore, the decreased concentration, viability, motility, and morphology of sperm in HFD rats indicated poor sperm quality.…”

Spirulina Platensis Affects Factors Involved in Spermatogenesis and Increases Ghrelin Receptors in Testis Tissue of Rats Fed a High-Fat Diet

“…Several papers are available, which report a significant decrease in testicular weight of rats fed with a HFD (Yan et al 2015, Gujjala et al 2016, beside those reporting no significant difference in testicular mass (Hu et al 2013, Campos-Silva et al 2015. A previous study (El-Desoky et al 2013) stated that administration of SP, suspended in water, by gavage for 60 consecutive days did not cause any significant difference in testis weights.…”

“…A PCNA immunohistochemistry study reported a significant decrease in cell proliferation in the testis of Wistar rats fed a HFD rich in saturated fatty acids (Campos-Silva et al 2015). In a previous study using TUNEL method, apoptotic index was reported to significantly increase in testis of rats fed a HFD (Yan et al 2015). In accordance with these studies, apoptotic index was significantly higher in HVO+CHL group (G4), and cell proliferation was significantly decreased in HVO (G2) and cholesterol (G3) groups in our study.…”

The insulin sensitiser metformin regulates chicken Sertoli and germ cell populations

“…Metformin may induce different effects depending on the age, stage of development, the metabolic status (insulin resistant or not), the species, dose and method of administration of the insulin sensitiser. Thus, there is data indicating that metformin administration in adult obese rats fed high-fat diet restores reproductive parameters (testosterone, E 2 , semen quality and testis weight; Yan et al 2015). In addition, there is a recent report of an increase in the percentage of intersex fish after metformin exposure during developmental stages at environmental doses, without clear effects on testosterone levels and gonad appearance (Niemuth et al 2015).…”