Zhao Yanling, Wang Jichen, Shi Shuai, Lan Xinting, Cheng Xiangyu, Li Lixia, Zou Yuanfeng, Jia Lanlan, Liu Wentao, Luo Qihui, Chen Zhengli, Huang Chao
Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.
Antioxidants (Basel). 2024 Apr 27;13(5):534. doi: 10.3390/antiox13050534.
Redox balance plays an important role in testicular homeostasis. While lots of antioxidant molecules have been identified as widely expressed, the understanding of the critical mechanisms for redox management in male germ cells is inadequate. This study identified LanCL2 as a major male germ cell-specific antioxidant gene that is important for testicular homeostasis. Highly expressed in the brain and testis, LanCL2 expression correlates with testicular maturation and brain development. LanCL2 is enriched in spermatocytes and round spermatids of the testis. By examining LanCL2 knockout mice, we found that LanCL2 deletion did not affect postnatal brain development but injured the sperm parameters of adult mice. With histopathological analysis, we noticed that LanCL2 KO caused a pre-maturation and accelerated the self-renewal of spermatogonial stem cells in the early stage of spermatogenesis. In contrast, at the adult stage, LanCL2 KO damaged the acrosomal maturation in spermiogenesis, resulting in spermatogenic defects with a reduced number and motility of spermatozoa. Furthermore, we show that this disruption of testicular homeostasis in the LanCL2 KO testis was due to dysbalanced testicular redox homeostasis. This study demonstrates the critical role of LanCL2 in testicular homeostasis and redox balance.
氧化还原平衡在睾丸内环境稳定中起着重要作用。虽然已鉴定出许多抗氧化分子广泛表达，但对雄性生殖细胞中氧化还原调控关键机制的了解仍不充分。本研究确定LanCL2是一种主要的雄性生殖细胞特异性抗氧化基因，对睾丸内环境稳定很重要。LanCL2在脑和睾丸中高表达，其表达与睾丸成熟和脑发育相关。LanCL2在睾丸的精母细胞和圆形精子细胞中富集。通过检查LanCL2基因敲除小鼠，我们发现LanCL2缺失不影响出生后脑发育，但损害成年小鼠的精子参数。通过组织病理学分析，我们注意到LanCL2基因敲除导致生精早期精原干细胞早熟并加速其自我更新。相反，在成年阶段，LanCL2基因敲除损害精子发生过程中的顶体成熟，导致精子数量减少和活力降低的生精缺陷。此外，我们表明LanCL2基因敲除睾丸中这种睾丸内环境稳定的破坏是由于睾丸氧化还原内环境稳定失衡所致。本研究证明了LanCL2在睾丸内环境稳定和氧化还原平衡中的关键作用。
