Department of Pharmacy, Health and Nutritional Sciences (Department of Excellence, Italian Law 232/2016), Arcavacata di Rende, Cosenza 87036, Italy.
Centro Sanitario, University of Calabria, Arcavacata di Rende, Cosenza 87036, Italy.
Hum Reprod. 2020 Sep 1;35(9):2072-2085. doi: 10.1093/humrep/deaa153.
Peroxisome proliferator-activated receptor gamma (PPARγ) acts as a ligand activated transcription factor and regulates processes, such as energy homeostasis, cell proliferation and differentiation. PPARγ 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 PPARγ. PPARγ 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 PPARγ 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, PPARγ protein is highly expressed in ejaculated spermatozoa, suggesting a possible role of PPARγ signaling in the regulation of sperm biology. This implies that both natural and synthetic PPARγ ligands may act directly on sperm improving its performance. Given the close link between energy balance and reproduction, activation of PPARγ may have promising metabolic implications in male reproductive functions. In this review, we first describe PPARγ expression in different compartments of the male reproductive axis. Subsequently, we discuss the role of PPARγ in both physiological and several pathological conditions related to the male fertility.
过氧化物酶体增殖物激活受体 γ（PPARγ）作为配体激活转录因子，调节能量平衡、细胞增殖和分化等过程。PPARγ与视黄酸 X 受体形成异二聚体与 DNA 结合，并被多不饱和脂肪酸和脂肪酸衍生物（如前列腺素）激活。此外，胰岛素增敏噻唑烷二酮类药物，如罗格列酮，是 PPARγ 的有效和特异性激活剂。PPARγ存在于下丘脑-垂体-睾丸轴和睾丸中，在睾丸中，已发现其在 Leydig 细胞中的水平较低，而在 Sertoli 细胞和生殖细胞中的水平较高。在正常的附睾和前列腺中报告了大量的 PPARγ，但在精囊腺中几乎检测不到该受体。有趣的是，在人和猪中，PPARγ 蛋白在射出的精子中高度表达，表明 PPARγ 信号在调节精子生物学方面可能发挥重要作用。这意味着天然和合成的 PPARγ 配体可能直接作用于精子，改善其性能。鉴于能量平衡和生殖之间的紧密联系，激活 PPARγ 可能对男性生殖功能的代谢具有广阔的前景。在这篇综述中，我们首先描述了 PPARγ 在男性生殖轴不同部位的表达。随后，我们讨论了 PPARγ 在生理和与男性生育力相关的几种病理条件下的作用。
