Altered Lipid Homeostasis in Sertoli Cells Stressed by Mild Hyperthermia

Abstract

Spermatogenesis is known to be vulnerable to temperature. Exposures of rat testis to moderate hyperthermia result in loss of germ cells with survival of Sertoli cells (SC). Because SC provide structural and metabolic support to germ cells, our aim was to test the hypothesis that these exposures affect SC functions, thus contributing to germ cell damage. In vivo, regularly repeated exposures (one of 15 min per day, once a day during 5 days) of rat testes to 43°C led to accumulation of neutral lipids. This SC-specific lipid function took 1–2 weeks after the last of these exposures to be maximal. In cultured SC, similar daily exposures for 15 min to 43°C resulted in significant increase in triacylglycerol levels and accumulation of lipid droplets. 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. Albeit temporary and potentially reversible, hyperthermia-induced SC structural and metabolic alterations may be long-lasting and/or extensive enough to respond for the decreased survival of the germ cells they normally foster.

Relevance of Fatty Acids to Sperm Maturation and Quality

“…Spermatogenesis is a complex process that involves the development of spermatozoa in the seminal tubules. The differentiation of spermatogonia into spermatozoa requires the participation of several cell types and the correct FA profile that contributes to a normal spermatogenetic process [117]. The importance of lipid composition, especially phospholipids, in the plasma membrane and semen plasma for spermatozoon function has since long been recognized [72].…”

Obesity, energy balance and spermatogenesis

“…Notably, all the concentrations of leptin decrease acetate production by Sertoli cells (Martins et al 2015), which could be associated with alteration in the cells lipid droplet accumulation. Accumulation of cytoplasmic lipid droplets, which has been associated with the elimination of germ cell-derived apoptotic bodies by phagocytosis (Wang et al 2006), was reported as one of the most striking deleterious effects of hyperthermia in Sertoli cells (Valles et al 2014). Interestingly, accumulation Ghrelin is produced in the gastrointestinal tract and impairs the testicular function by disrupting both the hypothalamic-pituitarythyroid (HPT) axis, affecting Sertoli and Leydig cell functions.…”

Effect of Dietaryn‐3Source on Rabbit Male Reproduction

“…They are incorporated into maturing germ cells by lysophosphatidic acid acyltransferase 3 [7]. An improper FA profile modifies the function of Sertoli cells as spermatogenesis supporters, influencing germ cell apoptosis [8]. Furthermore, during epididymal maturation, the lipid composition of the sperm membrane is remodelled and the saturation of FA increases from caput to the cauda epididymis, while the proportion of PUFA remains similar [9].…”