Pharmacological Relevance of Novel Biomarkers Associated with Diabetes-mellitus Related Infertility

Metabolic diseases are major public health problems both in developed and developing countries. Factors associated with lifestyle including physical inactivity and excessive consumption of high-energy diets are the primary causes for the increasing incidence of these pathologies. In parallel, an unprecedented decrease of fertility rates is also being witnessed. Male reproductive health is very sensitive to the insults induced by alterations in the metabolic status and the number of men suffering from metabolic diseases (such as diabetes mellitus and obesity) is dramatically high, being expected to increase even further in the next decades.

Diabetes mellitus is associated with a decrease in male reproductive potential and known to promote several sexual disorders, such as erectile dysfunction or retrograde ejaculation. Still, the “hidden effects” of this pathology on testicular physiology may lead to even more serious consequences for male fertility. Diabetes mellitus induces shifts in testicular metabolism, particularly in glucose metabolism, which is vital for the normal occurrence of spermatogenesis. So the maintenance of testicular glucose metabolism homeodynamics is of particular relevance; otherwise spermatogenesis may be arrested. For many years this issue was overlooked, but compelling evidence shows that spermatogenesis only occurs under a tight metabolic control. Thus, this subject is becoming a hot topic and will be on the spotlight in the next years. On the other hand, metabolic alterations induce pressure in biological systems whose responses are mediated by epigenetic modifications, particularly in sperm. These modifications are stable and can be passed to the subsequent generations, enhancing the transmission of phenotypes. Hence, the metabolic mechanisms responsible for the alterations in male reproductive health and subfertility/infertility in diabetic individuals deserve special attention.

p> This chapter will present cutting-edge information on the effects of diabetes mellitus in the testicular physiology and metabolism. It will be also discussed how this metabolic disease contributes to stable epigenetic changes that may alter not only male gametes’ function but also contribute to a potential transgenerational amplification of the current diabetes-related deleterious effects. Finally we will address the concept that testicular metabolism can be a potential pharmacologic target to counteract subfertility/infertility promoted by diabetes mellitus.

---

Keywords: Anti-diabetic drugs, Diabetes mellitus, Glucose metabolism, Highenergy diets, Hormonal control, Male infertility, Metabolic diseases, Metabolic reprogramming, Natural products, Oxidative stress, Reactive oxygen species, Sertoli cells, Sperm parameters, Spermatogenesis, Spermatozoa, Testicular biomarkers, Testicular metabolism, Therapeutic target, Transgenerational effects.