Dietary Cholesterol-Induced Post-Testicular Infertility

Abstract

This work shows that an overload of dietary cholesterol causes complete infertility in dyslipidemic male mice (the Liver X Receptor-deficient mouse model). Infertility resulted from post-testicular defects affecting the fertilizing potential of spermatozoa. Spermatozoa of cholesterol-fed lxr−/− animals were found to be dramatically less viable and motile, and highly susceptible to undergo a premature acrosome reaction. We also provide evidence, that this lipid-induced infertility is associated with the accelerated appearance of a highly regionalized epididymal phenotype in segments 1 and 2 of the caput epididymidis that was otherwise only observed in aged LXR-deficient males. The epididymal epithelial phenotype is characterized by peritubular accumulation of cholesteryl ester lipid droplets in smooth muscle cells lining the epididymal duct, leading to their transdifferentiation into foam cells that eventually migrate through the duct wall, a situation that resembles the inflammatory atherosclerotic process. These findings establish the high level of susceptibility of epididymal sperm maturation to dietary cholesterol overload and could partly explain reproductive failures encountered by young dyslipidemic men as well as ageing males wishing to reproduce.

Efficiency of Barley Bran and Oat Bran in Ameliorating Blood Lipid Profile and the Adverse Histological Changes in Hypercholesterolemic Male Rats

“…This result supported with previous studies suggesting a correlation between hypercholesterolemia and histological changes in the organs [44–46]. On the other hand, improvement in microscopic examination of tissues in groups fed on either oat bran or barley bran together with cholesterol.…”

Imbalanced lipid homeostasis in the conditional Dicer1 knockout mouse epididymis causes instability of the sperm membrane

“…This was further demonstrated after induction of the acrosome reaction, when the amount of cholesterol in control sperm was reduced by almost 50%, whereas the Dicer1 cKO sperm, which already lack an acrosome region, did not show any loss of cholesterol. Interestingly Ouvrier et al (57) also noticed increased membrane instability and immotility of sperm in a mouse model with altered lipid homeostasis in the proximal epididymis. Although these results were suggested to be caused by the accumulation of cholesteryl esters in the epididymal epithelium, the cholesterol:PUFA ratio of the sperm membrane was never measured, and the cause of infertility remained ambiguous (57).…”

Semen Quality and Sperm Function Loss by Hypercholesterolemic Diet Was Recovered by Addition of Olive Oil to Diet in Rabbit

“…It was reported that lipid increment in testis from obese mouse promotes apoptosis and increment in lipid droplets in spermatogonial cells [20]. But there are no studies to describe ultrastructural sperm abnormalities that are generated as a result of increased fat supply in this particular environment.…”

“…The deleterious impact on reproductive tissues has been studied in rabbits and other species [6], [7], [10], [14]–[18]. Changes in lipid content in testis [19] and epididymal cells [20] were reported in normal or genetically reprogrammed animals. But few papers were focused on the addition of natural products in the food as a protective diet, in order to avoid sperm alteration [14], [15].…”