Short-Chain Fatty Acids Promote Follicular Development by Alleviating Oxidative Stress-Induced Granulosa Cells Apoptosis in Sows.

BACKGROUND

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.

OBJECTIVES

This study aimed to investigate the mechanism by which SCFAs regulate the follicular development in sows.

METHODS

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.

RESULTS

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).

CONCLUSIONS

Propionate could alleviate sows' granulosa cells apoptosis via P300/PI3K/AKT signaling pathway.