文献类型：期刊文献

英文题名：Histone lactylation modulates apoptosis and stress response through PI3K/AKT signaling in GC-1 spermatogonial cells under hypoxia

作者：Tang, Qian[1,2,3];Wang, Xin[2,3,4];Zhang, Qiang[2,3];Li, Xitong[1,3];Gao, Ting[1,2,3];Wang, Ling[1]

第一作者：Tang, Qian

通信作者：Wang, L[1]

机构：[1]940th Hosp Joint Logist Support Force PLA, Reprod Med Ctr, Lanzhou 730050, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Clin Med Coll 1, Lanzhou 730000, Gansu, Peoples R China;[3]940th PLA, Gansu Prov Key Lab Stem Cell & Gene Therapy, Lanzhou 730050, Gansu, Peoples R China;[4]Support Force PLA, Burns & Plast Surg Dept, Lanzhou 730050, Gansu, Peoples R China

第一机构：940th Hosp Joint Logist Support Force PLA, Reprod Med Ctr, Lanzhou 730050, Gansu, Peoples R China

通信机构：[1]corresponding author), 940th Hosp Joint Logist Support Force PLA, Reprod Med Ctr, Lanzhou 730050, Gansu, Peoples R China.

年份：2026

卷号：24

期号：1

起止页码：61

外文期刊名：REVISTA INTERNACIONAL DE ANDROLOGIA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001784052400008)】；

基金：Internal Research Project of the 940th Hospital of the Joint Logistics Support Force (2023YXKY009); Lanzhou City Science and Technology Program (2023-ZD-182).

语种：英文

外文关键词：Histone lactylation; Hypoxia; Spermatogonia; Apoptosis; Lactate; GC-1 cells

摘要：Background: Histone lactylation is a recently identified epigenetic modification arising from lactate metabolism. This study aimed to determine whether lactate-induced histone lactylation contributes to the regulation of apoptosis in mouse Germ Cell-1 (GC-1) cells under hypoxic stress. Methods: A hypoxia-induced cell model was established to examine lactate accumulation, histone lactylation, and apoptosis in GC-1 cells. The experimental groups included the normoxia control (Con group), hypoxia (Hy group), hypoxia + sodium oxamate (Hy + Oxa group), and L-lactate treatment (Nala group). Lactate levels, histone lactylation, apoptosis-related gene and protein expression, and apoptosis rates were assessed by lactate assays, Western blot, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), and Annexin V/propidium iodide (PI) flow cytometry. Results: After 36 h of hypoxia, cell viability decreased to (58.55% +/- 6.20%) (p < 0.001). Hypoxia exposure caused increase in intracellular lactate concentration and induced histone lactylation (p < 0.01). Compared with the Con group, cells in the Hy group exhibited increased expression of pro-apoptotic markers Bax and caspase-3, reduced Bcl-2 expression, and higher apoptosis levels (p < 0.05). The Hy + Oxa group showed reduced histone lactylation and decreased apoptosis compared with the Hy group (p < 0.05). The Nala group exhibited patterns similar to the Hy group, including increased histone lactylation and enhanced apoptosis (p < 0.05), confirming that lactate regulates apoptosis through histone lactylation. Furthermore, both hypoxia and exogenous lactate significantly reduced the ratios of phosphorylated phosphatidylinositol 3-kinase (p-PI3K)/PI3K and phosphorylated protein kinase B (p-AKT)/AKT, whereas oxamate partially restored their activity (p < 0.05). Conclusions: Hypoxia-induced lactate accumulation promotes apoptosis of GC-1 cells by enhancing histone lactylation, particularly at the H3K18 site, partly through suppression of the PI3K/AKT signaling pathway. These findings provide new mechanistic insights into hypoxia-associated male infertility and suggest that histone lactylation may represent a potential therapeutic target.