Mild hyperthermia alters lipid metabolism of sertoli cells

VALLES, ANA SOFIA.; AVELDAÑO, M.I.; FURLAND, N.E

Congreso; 56 th international conference on the bioscience of lipids; 2015

Spermatogenesis is known to be vulnerable to temperature. Because sertoli cells (SC) provide structural and metabolic support to germ cells (GC), our aim was to test the hypothesis that mild hyperthermia exposures affect SC functions, thus contributing to GCl damage. In cultured TM4 SC, regularly repeated hyperthermia exposures (immersions of cell plates in a water bath at 43 °C, 15 min per day, once a day during 5 days) resulted in significant increase in triacylglycerol (TAG) levels and accumulation of lipid droplets (LD). After incubations with [3H]arachidonate, the labeling of cardiolipin decreased more than that of other lipid classes. Another specifically mitochondrial lipid metabolic function, fatty acid oxidation, also declined. These lipid changes suggested that temperature affects SC mitochondrial physiology, which was confirmed by significantly increased degrees of membrane depolarization and ROS production. This concurred with reduced expression of two SC-specific proteins, transferrin, and Wilms´ Tumor 1 protein, markers of SC secretion and differentiation functions, respectively, and with an intense SC cytoskeletal perturbation, evident by loss of microtubule network (α-tubulin) and microfilament (f-actin) organization. The intermediate filament network (vimentin) was also modified after the hyperthermia treatment showing a more peripheral distribution. Interestingly these alterations were only temporary and revert shortly after the hyperthermia treatment is finalized. Next we focused on understanding the mechanism of how hyperthermia modifies the lipid metabolism of SC. Firstly, we invested whether the lipid alterations found on SC after the hyperthermia exposures were directly linked with the cytoskeleton rearrangements visualized after receiving the hyperthermia treatment. For this purpose, we studied the effect of nocodazole, a drug that interferes with the polymerization of microtubules, and also observed significant increase in TAG levels, accumulation of LD; mitochondrial physiology alterations, reduced expression of transferrin and re organization of the cytoskeleton of SC. These effects were also temporary and SC recovered shortly after the exposition to nocodazole was finalized.Thus, the correct organization/ arrangement of the cytoskeleton plays a key role in the lipid metabolism of SC