Glycerol and testicular activity: the good, the bad and the ugly

Over the past decades, there have been several studies suggesting that semen quality is declining. Interestingly, these observations are paired with a significant increase in the number of individuals diagnosed with metabolic diseases, including obesity and diabetes mellitus. Hence, it is tempting to hypothesize that obesity and its associated comorbidities and risk factors (such as a hypercaloric diets) impair the homeostasis of the male reproductive health, with a possible direct effect on the testes. The blood and interstitial fluids of obese individuals usually have increased levels of glycerol, notably due to triglyceride and phospholipid catabolism and high fructose intake. Glycerol is metabolized via intermediary metabolism by a group of reactions centred at the glycerol-3-phosphate shuttle, which links the metabolic pathway of glucose, lipids and oxidative phosphorylation, illustrating its high relevance for biological systems. Glycerol enters and exits the cells by the action of specialized carriers, known as aquaglyceroporins, whose functional importance for male reproductive health has emerged in the last few years. Notably, glycerol has antispermatogenic properties. When present in high concentration in the testis, it causes blood-testis barrier disruption, impairing tubular fluid homeostasis. Nevertheless, glycerol metabolism in testicular cells remains a matter of debate. Herein we discuss previous and current research concerning the role of glycerol and its metabolism in testicular cells, and how it can influence testicular activity.