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.
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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.
