Qin Wenxia, Xu Baoyang, Lei Xinyu, Yan Xianghua
National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Frontiers Science Center for Animal Breeding and Sustainable Production, Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China.
College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, China.
J Nutr. 2025 Aug;155(8):2611-2621. doi: 10.1016/j.tjnut.2025.05.035. Epub 2025 May 28.
The fate of granulosa cells determines ovarian follicular development outcomes. Our previous study suggested that gut microbiota-derived short-chain fatty acids (SCFAs) positively correlated with sows' follicular maturation, but the underlying mechanism remains unclear.
This study aimed to investigate the mechanism by which SCFAs regulate the follicular development in sows.
Eighty L × Y sows (95 d old) were fed a basal diet (Ctrl, 40 gilts) or a basal diet supplemented with 0.13% acetate, 0.11% propionate, and 0.09% butyrate (SCFAs, 40 gilts). At third estrus, 13 gilts (6 from Ctrl and 7 from SCFAs) were killed for determination of granulosa cell apoptosis and SCFAs concentrations in follicular fluid. Granulosa cell apoptosis model with transcriptome and inhibitors were employed to dissect the mechanism by which SCFAs regulate granulosa cell apoptosis.
SCFAs group had fewer granulosa cell apoptosis and caspase-3 concentration (0.43 compared with 0.75), but higher B-cell lymphoma 2 (BCL2) concentration (0.81 compared with 0.55) in sows' granulosa cells compared with the Ctrl group (P < 0.05). The follicular fluid concentrations of acetate (89.31 compared with 61.46), propionate (6.25 compared with 3.40), and butyrate (11.69 compared with 6.31) were increased in SCFAs group than in Ctrl group (P < 0.05). Among SCFAs, propionate had a better effect on alleviating granulosa cell apoptosis than the others, and meanwhile inhibited histone deacetylases activity, enhanced histone acetyltransferase activity, and elevated P300 concentration in vitro (P < 0.05). Transcriptomic analysis revealed that propionate-induced differentially expressed genes were significantly enriched in the phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) pathway (P < 0.05). Propionate increased concentrations of PI3K (P < 0.05), AKT (P < 0.01), and BCL-2 (P < 0.05), whereas it decreased concentrations of Caspase-3 (P < 0.05). Moreover, inhibitors against P300 and PI3K both alleviated granulosa cell apoptosis and restrained the antiapoptosis effect of propionate (P < 0.05).
Propionate could alleviate sows' granulosa cells apoptosis via P300/PI3K/AKT signaling pathway.
颗粒细胞的命运决定了卵泡发育的结果。我们之前的研究表明，肠道微生物群衍生的短链脂肪酸（SCFAs）与母猪卵泡成熟呈正相关，但其潜在机制仍不清楚。
本研究旨在探讨SCFAs调节母猪卵泡发育的机制。
80头L×Y母猪（95日龄）被喂食基础日粮（对照组，40头后备母猪）或添加0.13%乙酸盐、0.11%丙酸盐和0.09%丁酸盐的基础日粮（SCFAs组，40头后备母猪）。在第三次发情期，处死13头后备母猪（对照组6头，SCFAs组7头），用于测定颗粒细胞凋亡和卵泡液中SCFAs浓度。采用转录组和抑制剂构建颗粒细胞凋亡模型，以剖析SCFAs调节颗粒细胞凋亡的机制。
与对照组相比，SCFAs组母猪颗粒细胞凋亡和半胱天冬酶-3浓度较低（分别为0.43和0.75），但B细胞淋巴瘤2（BCL2）浓度较高（分别为0.81和0.55）（P<0.05）。SCFAs组卵泡液中乙酸盐（分别为89.31和61.46）、丙酸盐（分别为6.25和3.40）和丁酸盐（分别为11.69和6.31）浓度高于对照组（P<0.05）。在SCFAs中，丙酸盐在减轻颗粒细胞凋亡方面比其他物质效果更好，同时在体外抑制组蛋白脱乙酰酶活性，增强组蛋白乙酰转移酶活性，并提高P300浓度（P<0.05）。转录组分析显示，丙酸盐诱导的差异表达基因在磷酸肌醇3激酶（PI3K）-蛋白激酶B（AKT）通路中显著富集（P<0.05）。丙酸盐增加了PI3K（P<0.05）、AKT（P<0.01）和BCL-2（P<0.05）的浓度，而降低了半胱天冬酶-3的浓度（P<0.05）。此外，针对P300和PI3K的抑制剂均减轻了颗粒细胞凋亡，并抑制了丙酸盐的抗凋亡作用（P<0.05）。
丙酸盐可通过P300/PI3K/AKT信号通路减轻母猪颗粒细胞凋亡。
