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

Area of Science:

• Reproductive Biology
• Animal Science
• Molecular Endocrinology

Background:

• Granulosa cell fate is critical for ovarian follicular development.
• Gut microbiota-derived short-chain fatty acids (SCFAs) are linked to improved sow follicular maturation, but the mechanism is unknown.

Purpose of the Study:

• To elucidate the mechanism by which SCFAs regulate granulosa cell apoptosis and follicular development in sows.

Main Methods:

• Sows were fed either a basal diet or a diet supplemented with acetate, propionate, and butyrate (SCFAs).
• Granulosa cell apoptosis, SCFA concentrations, and molecular signaling pathways (P300, PI3K/AKT) were analyzed.
• Transcriptomic analysis and inhibitor studies were used to dissect the underlying molecular mechanisms.

Main Results:

• SCFA supplementation reduced granulosa cell apoptosis and caspase-3 levels, while increasing BCL-2 levels.
• Propionate demonstrated the most significant anti-apoptotic effect, inhibiting histone deacetylase activity and enhancing histone acetyltransferase activity.
• Propionate upregulated the P300/PI3K/AKT pathway, leading to increased PI3K, AKT, and BCL-2, and decreased Caspase-3.

Conclusions:

• Propionate alleviates granulosa cell apoptosis in sows through the P300/PI3K/AKT signaling pathway.
• This study provides mechanistic insights into the role of SCFAs in regulating ovarian follicular development.