Evaluation of testicular glycogen storage, FGF21 and LDH expression and physiological parameters of sperm in hyperglycemic rats treated with hydroalcoholic extract of Securigera Securidaca seeds, and Glibenclamide

Mohammad Babaei,Alireza Nourian,Iraj Alipourfard,Elham Bahreini,Shahin Alizadeh-Fanalou,Sahar Yarahmadi,Navid Farahmandian,Mohsen Nabi-Afjadi

doi:10.1186/s12958-021-00794-1

Abstract

Structural and physiological changes in sperm and semen parameters reduce fertility in diabetic patients. Securigera Securidaca (S. Securidaca) seed is a herbal medicine with hypoglycemic, antioxidant, and anti-hypertensive effects. The question now is whether this herbal medicine improves fertility in diabetic males. The study aimed to evaluate the effects of hydroalcoholic extract of S. Securidaca seeds (HESS), glibenclamide and a combination of both on fertility in hyperglycemic rats by comparing histological and some biochemical changes in testicular tissue and sperm parameters. The treatment protocol included administration of three doses of HESS and one dose of glibenclamide, as well as treatment with both in diabetic Wistar diabetic rats and comparison of the results with untrated groups. The quality of the testicular tissue as well as histometric parameters and spermatogenesis indices were evaluated during histopathological examination. Epididymal sperm analysis including sperm motility, viability, abnormalities, maturity, and chromatin structure were studied. The effect of HESS on the expression of LDH and FGF21 genes and tissue levels of glycogen, lactate, and total antioxidant capacity in testicular tissue was investigated and compared with glibenclamide. HESS improved sperm parameters in diabetic rats but showed little restorative effect on damaged testicular tissue. In this regard, glibenclamide was more effective than the highest dose of HESS and its combination with HESS enhanced its effectiveness so that histological tissue characteristics and sperm parameters were were comparable to those of healthy rats. The expression level of testicular FGF21 gene increased in diabetic rats, which intensified after treatment with HESS as well as glibenclamide. The combination of HESS and glibenclamide restored the expression level of testicular LDH gene, as well as tissue storage of glycogen, lactate and LDH activity, and serum testosterone to the levels near healthy control. S. Securidaca seeds can be considered as an effective supplement in combination with hypoglycemic drugs to prevent infertility complications in diabetes.

Highlights

A proven feature of diabetes mellitus (DM) is the reduction in male fertility, both in terms of semen parameters and sperm structures [1, 2]
The process of spermatogenesis is strictly regulated by the function of Sertoli cells, which maintain the division of germ cells and provide supporting factors such as hormones, various pro, and anti-apoptotic agents, and energetic substrates
Sertoli cells metabolize glucose to pyruvate through cytoplasmic glycolysis, immediately reduce it to lactate by lactate dehydrogenase (LDH), and export it to the intratubular fluid by monocarboxylate transporter 4 (MCT4)

Summary

Introduction

A proven feature of diabetes mellitus (DM) is the reduction in male fertility, both in terms of semen parameters and sperm structures [1, 2] These effects are described as devastating changes in spermatogenesis. The released lactate is taken up by germ cells via MCTs and converted to pyruvate, while the resulting NADH can modify the redox status of germ cells. This metabolic pattern is referred to as “Warburg-like metabolism” and is frequently observed in cancer cells [10,11,12]. Galardo et al [13] showed that lactate increased mRNA levels of MCT2 and LDH-C, but not MCT4 and LDH-A

Methods

Results

Discussion

Conclusion