Testicular STAC3 regulates Leydig cell steroidogenesis through potentiating mitochondrial membrane potential and StAR...

Area of Science:

• Reproductive biology
• Cellular and molecular biology
• Endocrinology

Background:

• SH3 and cysteine-rich protein 3 (STAC3) is known for its role in skeletal muscle excitation-contraction coupling.
• Its potential functions outside of muscle tissue remain largely unexplored.

Purpose of the Study:

• To investigate the expression and function of STAC3 in spermatogenesis and male reproductive health.
• To elucidate the role of STAC3 in testicular steroidogenesis and Leydig cell function.

Main Methods:

• STAC3 expression analysis in rodent and human testes.
• Selective Leydig cell ablation using ethylene dimethane sulfonate (EDS).
• In vivo lentiviral vector-mediated STAC3 knockdown in rats.
• In vitro studies using primary Leydig cells and TM3^Stac3-/- cells.

Main Results:

• STAC3 is expressed in testicular interstitial Leydig cells (LCs) and its expression is dependent on LC presence.
• STAC3 suppression in vivo significantly reduced testosterone production, leading to oligozoospermia and asthenospermia, impairing male fertility.
• STAC3 deficiency in LCs attenuated mitochondrial membrane potential and StAR processing, suggesting disrupted mitochondrial homeostasis.

Conclusions:

• STAC3 plays a critical, previously unrecognized role in male reproductive function.
• STAC3 is essential for testicular steroidogenesis by maintaining mitochondrial homeostasis in Leydig cells.
• STAC3 represents a novel link between mitochondrial function and testosterone production.