SPINK3-sperm interaction determines a stable sperm subpopulation with intact CatSper channel: SPINK3 stabilizes...

Area of Science:

• Reproductive Biology
• Molecular Endocrinology
• Sperm Physiology

Background:

• Sperm capacitation requires proteolytic remodeling of membrane proteins.
• The CatSper calcium channel is crucial for sperm hyperactivation and male fertility.
• SPINK3 is a known decapacitation factor that inhibits premature capacitation.

Purpose of the Study:

• To identify physiological inhibitors of CATSPER1 processing.
• To elucidate the role of SPINK3 in regulating sperm capacitation and CatSper channel function.
• To understand SPINK3's mechanism of action on sperm membranes.

Main Methods:

• Analysis of SPINK3's effect on CATSPER1 cleavage in mouse sperm.
• Localization studies of SPINK3 on the sperm surface.
• Assessment of SPINK3's impact on membrane organization and cholesterol efflux.

Main Results:

• SPINK3 inhibits capacitation-induced cleavage of CATSPER1.
• SPINK3 preserves sperm subpopulations with intact CatSper channels and delayed pTyr development.
• SPINK3 localizes to the sperm principal piece membrane in a CatSper-dependent manner.
• SPINK3 stabilizes sperm membranes and delays cholesterol efflux.

Conclusions:

• SPINK3 is the first identified physiological inhibitor of CATSPER1 processing.
• SPINK3 acts as a multifunctional regulator of sperm capacitation and function.
• SPINK3 shapes sperm subpopulations within the female reproductive tract, impacting male fertility.