National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People's Republic of China.
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
Reproduction. 2020 Dec;160(6):931-941. doi: 10.1530/REP-20-0097.
Asthenozoospermia (AS), defined as low-motility spermatozoa in the ejaculate, is a frequent cause of human male infertility. DJ-1 (also known as PARK7), a protein highly associated with male sterility, binds to the mitochondrial complex I subunit to protect mitochondrial function. However, its involvement in spermatogenesis has not been fully elucidated. Previously, the levels of DJ-1 were shown to be significantly decreased in testicular tissues of rats with ornidazole (ORN)-induced AS. Here, we used a rat model to investigate the localization and expression levels of DJ-1 and its interacting NDUFS3 and NDUFA4 mitochondrial complex I subunits, as well as AS-induced metabolic alterations in testicular tissues. ORN significantly reduced the levels of DJ-1 in the nucleus of secondary spermatocytes, while increasing the expression of NDUFS3 in the cytoplasm of primary spermatocytes. Further, NDUFA4 showed higher expression after treatment with ORN. The principal ORN-induced changes in metabolic small molecules related to the accumulation of glucose, glutamine, and N-acetyl aspartate, enhancement of purine pathway, increase of the phosphatidic acid (PA) (18:0/18:1), phosphatidylethanolamine (PE) (16:0/18:1), and PA (18:0/20:4) lipid metabolites, and imbalance in the concentrations of Na+ and K+. However, we did not observe any abnormalities of certain small metabolic molecules and metal ions in semen samples from patients with AS. In conclusion, these results suggest that DJ-1 deficiency in testicular tissues might be closely related to the localization of NDUFS3 and content of NDUFA4, thus causing abnormalities in the mitochondrial energy metabolism and multiple other metabolic pathways.
弱精子症（AS）定义为精液中运动能力低下的精子，是导致人类男性不育的常见原因。DJ-1（也称为 PARK7）是一种与男性不育高度相关的蛋白质，它与线粒体复合物 I 亚基结合以保护线粒体功能。然而，其在精子发生中的作用尚未完全阐明。先前的研究表明，硝唑（ORN）诱导的 AS 大鼠睾丸组织中 DJ-1 水平显著降低。在这里，我们使用大鼠模型研究了 DJ-1 及其相互作用的 NDUFS3 和 NDUFA4 线粒体复合物 I 亚基在睾丸组织中的定位和表达水平，以及 AS 诱导的代谢改变。ORN 显著降低了次级精母细胞细胞核中 DJ-1 的水平，而增加了初级精母细胞质中 NDUFS3 的表达。此外，ORN 处理后 NDUFA4 的表达增加。与葡萄糖、谷氨酰胺和 N-乙酰天冬氨酸积累相关的代谢小分子的主要 ORN 诱导变化，嘌呤途径增强，磷酸脂酰乙醇胺（PE）（16：0/18：1）和 PA（18：0/20：4）脂质代谢物增加，以及 Na+和 K+浓度失衡。然而，我们没有观察到 AS 患者精液样本中某些小代谢分子和金属离子的异常。总之，这些结果表明睾丸组织中 DJ-1 的缺乏可能与 NDUFS3 的定位和 NDUFA4 的含量密切相关，从而导致线粒体能量代谢和其他多种代谢途径的异常。
