猪精液品质受多种因素影响，其中细菌感染产生的细菌内毒素（LPS）可引起精子凋亡，导致繁殖效率下降。LPS调节线粒体氧化磷酸化（OXPHOS）诱发线粒体氧化损伤和细胞凋亡，但确切机制尚未阐明。资料表明，线粒体转录因子A（TFAM）定位于线粒体并调节线粒体DNA（mtDNA）转录是OXPHOS发生的关键步骤。由此推测LPS通过干扰TFAM线粒体定位，导致OXPHOS异常活化，诱发猪精子氧化损伤和凋亡。基于该假说，本课题将测定精液中LPS浓度并建立猪精子培养模型，从TFAM线粒体转位及泛素化修饰双重角度入手，阐明LPS调控TFAM线粒体定位的分子机制；检测TFAM调节猪精子mtDNA转录、OXPHOS、氧化损伤和凋亡的过程；针对关键靶点筛选有效缓解LPS诱发精子氧化损伤的调节剂并验证其功能。研究结果有助于揭示LPS诱发猪精子凋亡的细胞和分子机制，为提高猪精子质量、提升繁殖效率提供解决方案。

There are many different factors that can influence boar sperm quality. Gram negative bacterial endotoxin (LPS) could lead to alteration semen parameters, induction of apoptosis in spermatozoa, and decrease of reproductive performance of pigs. LPS attenuate oxidative stress and apoptosis is associated with alterations in mitochondrial oxidative phosphorylation (OXPHOS). However, the exact mechanism of this process is not well studied. Localization of the Mitochondrial Transcription Factor A (TFAM) to mitochondria and binds to mitochondrial DNA (mtDNA) was the key step of mitochondrial OXPHOS. Thus, we hypothesized that LPS induces abnormal activation of OXPHOS and sperm oxidative damage by regulating mitochondrial localization of TFAM. In this project, we will develop a boar sperm culture model to detect the regulation of LPS on mitochondrial translocation and ubiquitination of TFAM. Furthermore, the effects of TFAM on mtDNA transcription, OXPHOS, oxidative damage and sperm apoptosis will be studied. Finally, choose physiological regulators which work to alleviate LPS-induced oxidative stress in boar sperm. The outcome of this project will provide new insights on the molecular mechanisms underlying the LPS-induced sperm apoptosis and also offer possible solutions for improve the quality of boar sperm.