State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing 211166, China.
Shanghai Key Laboratory of Reproductive Medicine, Department of Histoembryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Asian J Androl. 2024 Mar 1;26(2):212-219. doi: 10.4103/aja202350. Epub 2023 Oct 24.
Male germ cells employ specific metabolic pathways throughout their developmental stages. In a previous study, we discovered heightened expression of pyruvate kinase M (PKM), a pivotal glycolytic enzyme, in spermatogonia and spermatids. To gain deeper insights into PKM's roles in spermatogenesis, sperm function, and male fertility, we engineered a conditional-knockout mouse model ( Pkm -vKO mice) to selectively disrupt the Pkm gene within germ cells. Despite maintaining regular testicular histology and sperm morphology, the male Pkm -vKO mice were infertility, characterized by significant impairments in sperm motility and adenosine triphosphate (ATP) generation. In addition, Pkm -null spermatozoa exhibited similar deficits in protein tyrosine phosphorylation linked to capacitation, as well as compromised performance in in vitro fertilization experiments. To conclude, PKM's presence is not obligatory for the entirety of spermatogenesis in male germ cells; however, it emerges as a critical factor influencing sperm motility and overall male fertility.
雄性生殖细胞在其发育阶段采用特定的代谢途径。在之前的研究中，我们发现丙酮酸激酶 M（PKM），一种关键的糖酵解酶，在精原细胞和精子细胞中表达水平升高。为了更深入地了解 PKM 在精子发生、精子功能和男性生育力中的作用，我们构建了一种条件性敲除小鼠模型（Pkm-vKO 小鼠），以便在生殖细胞中特异性敲除 Pkm 基因。尽管睾丸组织学和精子形态保持正常，但雄性 Pkm-vKO 小鼠不育，其精子运动和三磷酸腺苷（ATP）生成显著受损。此外，Pkm 缺失的精子在与获能相关的蛋白质酪氨酸磷酸化方面表现出类似的缺陷，并且在体外受精实验中的表现也受损。总之，PKM 的存在对于雄性生殖细胞的整个精子发生过程并非必需，但它是影响精子运动和整体男性生育力的关键因素。
