Modulation of diabetes-mellitus-induced male reproductive dysfunctions in experimental animal models with medicinal plants

Abstract

Today diabetes mellitus has emerged as a major healthcare problem throughout the world. It has recently broken the age barrier and has been diagnosed in younger people also. Sustained hyperglycemia is associated with many complications including male reproductive dysfunctions and infertility. Numerous medicinal plants have been used for the management of the diabetes mellitus in various traditional system of medicine and in folklore worldwide as they are a rich source of bioactive phytoconstituents, which lower blood glucose level and/or also act as antioxidants resulting in the amelioration of oxidative-stress-induced diabetic complications. The present review describes the ameliorative effects of medicinal plants or their products, especially on male reproductive dysfunctions, in experimental diabetic animal models.

INTRODUCTION

Diabetes mellitus (DM) is a chronic, complicated metabolic disorder characterized by hyperglycemia, which often results from defects in insulin secretion, insulin action, or both. Moreover, DM is associated with severe disturbances of carbohydrate, fat, and protein metabolism.[1]

Diabetes is rapidly emerging as a major public health challenge and demands special attention towards its management. According to the diabetic atlas of the International Diabetic Federation, 366 million people were affected by diabetes worldwide in 2011, and diabetes prevalence is expected to 522 million by 2030.[2] Furthermore, the increasing prevalence of diabetes mellitus in children and adolescents is also of concern. Poorly managed diabetes can lead to a large number of complications including retinopathy, neuropathy, nephropathy, cardiovascular diseases, and male impotency.[3,4]

A large number of studies, both in diabetic men and animal models indicate that DM causes male infertility based on impotency, retrograde ejaculation, and hypogonadism. DM may affect male reproductive functions at multiple levels including variation in sperm quality, altered spermatogenesis, morphological changes in testes, altered glucose metabolism in Sertoli-blood testes barrier, reduced testosterone, ejaculatory dysfunction, and reduced libido.[5,6,7,8,9,10,11,12,13] Several clinical and animal studies have focused on the molecular mechanism responsible for the alterations induced by DM in male reproductive potential including endocrine disorders, neuropathy, and increased oxidative stress.[12]

DM-induced adverse effects on male reproductive functions might be mediated through hormonal alterations in the hypothalamic-pituitary-gonadal axis or through the direct interactions of insulin with the testes and sperm cells, as both the testes and sperms themselves produce insulin.[11] Insulin expression in the testes also seems to be affected by diabetes.[14] Both diabetic men and knockout mice had notably impaired spermatogenesis, increased germ cell depletion, and Sertoli cell vacuolization, suggesting that insulin may have an important role in spermatogenesis.[6,15] It is still unclear whether the effects of diabetes on male fertility are mediated through testicular insulin insufficiency or through systemic effects of diabetes.[16,17,18]

Furthermore, oxidative stress may play a pathogenic role in diabetes-related male reproductive function abnormalities.[12] Studies have shown that men suffering from diabetes have sperms with greater DNA fragmentation and an increase in advanced glycation end products and their receptors (RAGE) leading to deterioration of sperm quality, sperm functions coupled with changes in testicular metabolite levels and spermatogenic gene expression.[19,20,21] Several studies have shown that antioxidant treatment improves glycemic index, reduces diabetic complications, and protects components from oxidative damage.[22,23]

The use of plants in the management of diabetes is well documented, which is primarily due to anti-hyperglycemic and/or oxygen radical scavenging of their various phytoconstituents through various mechanisms.[24,25] Medicinal plants provide better alternatives as they are less toxic, easily available and affordable.[26]

A brief review of the medicinal plants having ameliorative effects on blood sugar levels and/or male reproductive functions in experimental diabetic animals is presented in Table 1.

Table 1.

Review of the literature of various plants/herbs showing modulatory effect on reproductive dysfunctions in male diabetic animals

CONCLUSION

From the results of the above studies, it can be concluded that supplementation of medicinal plant products, extracts, or herbal formulations may be useful in alleviation of DM-induced complications, especially male reproductive dysfunction, by virtue of their antidiabetic, antioxidant, and androgenic activities of various bioactive phytoconstituents.