Apigenin improves testosterone synthesis by regulating endoplasmic reticulum stress.

Area of Science:

• Reproductive Biology
• Endocrinology
• Metabolic Diseases

Background:

• Male obesity is a growing epidemic linked to infertility.
• Obesity can disrupt hormone balance, particularly testosterone levels.
• Natural products show promise in managing metabolic diseases.

Purpose of the Study:

• To investigate apigenin's potential to counteract high-fat diet-induced testicular dysfunction.
• To explore the mechanisms involving endoplasmic reticulum stress (ERS) and testosterone synthesis.
• To assess apigenin's effects on obesity and lipid metabolism.

Main Methods:

• Established a murine model of obesity using high-fat diet (HFD).
• Administered apigenin (10 mg/kg) and assessed physiological, histological, and molecular changes.
• Utilized in vitro studies on murine Leydig cells (TM3) with free fatty acids (FFAs).
• Employed ChIP, qPCR, and gene silencing to analyze gene expression and protein interactions.

Main Results:

• Apigenin (AP) administration reduced body weight and improved lipid profiles in obese mice.
• AP ameliorated testicular pathology and restored testosterone-related protein levels.
• In vitro, AP relieved ERS and recovered testosterone synthesis in Leydig cells.
• AP protected against ERS-induced suppression of steroidogenic STAR expression via CHOP modulation.

Conclusions:

• Apigenin demonstrates significant potential in alleviating high-fat diet-induced obesity and male testicular dysfunction.
• Apigenin's protective effects are linked to mitigating endoplasmic reticulum stress and restoring testosterone synthesis.
• Targeting ERS and enhancing testosterone production are key mechanisms for apigenin's therapeutic action.