Peroxisome proliferator-activated receptor gamma expression along the male genital system and its role in male fertility

Peroxisome proliferator-activated receptor gamma (PPARc) acts as a ligand activated transcription factor and regulates processes, such as energy homeostasis, cell proliferation and differentiation. PPARc binds to DNA as a heterodimer with retinoid X receptor and it is activated by polyunsaturated fatty acids and fatty acid derivatives, such as prostaglandins. In addition, the insulin-sensitizing thiazolidinediones, such as rosiglitazone, are potent and specific activators of PPARc. PPARc is present along the hypothalamic-pituitary-testis axis and in the testis, where low levels in Leydig cells and higher levels in Sertoli cells as well as in germ cells have been found. High amounts of PPARc were reported in the normal epididymis and in the prostate, but the receptor was almost undetectable in the seminal vesicles. Interestingly, in the human and in pig, PPARc protein is highly expressed in ejaculated spermatozoa, suggesting a possible role of PPARc signaling in the regulation of sperm biology. This implies that both natural and synthetic PPARc ligands may act directly on sperm improving its performance. Given the close link between energy balance and reproduction, activation of PPARc may have promising metabolic implications in male reproductive functions. In this review, we first describe PPARc expression in different compartments of the male reproductive axis. Subsequently, we discuss the role of PPARc in both physiological and several pathological conditions related to the male fertility.