Functional importance of palmitoyl protein thioesterase 1 (PPT1) expression by Sertoli cells in mediating cholesterol metabolism and maintenance of sperm quality
Functional importance of palmitoyl protein thioesterase 1 (PPT1) expression by Sertoli cells in mediating cholesterol metabolism and maintenance of sperm quality
复制标题
支持细胞表达棕榈酰蛋白硫酯酶 1 (PPT1) 在介导胆固醇代谢和维持精子质量中的功能重要性
DOI：
10.1002/mrd.23173
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发表时间：
2019
影响因子：
2.5
通讯作者：
Liu Yue
中科院分区：
文献类型：
--
作者：
Zhao Wenzhen;Su Juan;Wang Yuntao;Qian Tijun;Liu Yue
支持细胞是精子上皮中的一种护理细胞，通过向发育中的生殖细胞提供营养和能量支持，对维持精子发生至关重要。支持细胞功能障碍可导致男性精子发生紊乱和生育能力下降。在这项研究中，我们重点研究了棕榈酰蛋白硫酯酶1 (PPT1)，一种溶酶体去棕榈酰化酶，在支持细胞中的表达和功能。在这里，我们证明了PPT1在Sertoli细胞中的表达对胆固醇治疗是有反应的，并且在Sertoli细胞中特异性敲除PPT1会导致男性生育能力低下，与精子质量差和精子畸形率高相关。具体来说，Ppt1缺乏导致细胞变差，并伴有溶酶体异常积聚和支持细胞胆固醇水平升高。此外，Ppt1缺乏导致发育中的生殖细胞与授精上皮内的支持细胞粘附不良，这可能是由于精子数量和活力下降以及精子头畸形发生率高而导致男性生育能力降低的原因。综上所述，PPT1通过调节支持细胞的溶酶体功能和胆固醇代谢来影响精子质量和男性生育能力。
Sertoli cells are a type of nurse cell in the seminiferous epithelium that are crucial for sustaining spermatogenesis by extending nutritional and energy support to the developing germ cells. Dysfunction of Sertoli cells could cause disordered spermatogenesis and reduced fertility in males. In this study, we focused on the expression and function of palmitoyl protein thioesterase 1 (PPT1), a lysosomal depalmitoylating enzyme, in Sertoli cells. Here, we show that PPT1 expression in Sertoli cells is responsive to cholesterol treatment and that specific knockout of Ppt1 in Sertoli cells causes male subfertility associated with poor sperm quality and a high ratio of sperm deformity. Specifically, Ppt1 deficiency leads to poor cell variably accompanied with abnormal lysosome accumulation and increased cholesterol levels in Sertoli cells. Further, Ppt1 deficiency results in poor adhesion of developing germ cells to Sertoli cells in the seminiferous epithelium, which is likely to be responsible for the reduced male fertility as a consequence of declines in sperm count and motility as well as a high incidence of sperm head deformity. In summary, PPT1 affects sperm quality and male fertility through regulating lysosomal function and cholesterol metabolism in Sertoli cells.