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SPINK3-Sperm Interaction Determines a Stable Sperm Subpopulation With Intact CatSper Channel.

Anabella R Nicolli1, Xiaofang Huang2, Lucia Zalazar1

  • 1Facultad de Ciencias Exactas y Naturales, Instituto de Investigaciones Biológicas (IIB-FCEyN/CONICET), Universidad Nacional de Mar del Plata, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mar del Plata, Buenos Aires, Argentina.

Journal of Cellular Physiology
|January 22, 2026
PubMed
Summary
This summary is machine-generated.

The seminal protease inhibitor SPINK3 prevents premature sperm capacitation by blocking CATSPER1 processing. This action preserves sperm function, highlighting SPINK3

Keywords:
CATSPER1SPINK3decapacitation factorsmembrane stabilizationprotease inhibitionsperm capacitation

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Area of Science:

  • Reproductive Biology
  • Molecular Endocrinology
  • Sperm Physiology

Background:

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

Purpose of the Study:

  • To identify the physiological inhibitor of CATSPER1 processing during sperm capacitation.
  • To elucidate the role of SPINK3 in regulating CatSper channel function and sperm capacitation.

Main Methods:

  • Investigated SPINK3's inhibitory effect on CATSPER1 cleavage in mouse sperm.
  • Analyzed the localization and membrane effects of SPINK3.
  • Assessed the impact of SPINK3 on sperm capacitation markers like pTyr development and cholesterol efflux.

Main Results:

  • SPINK3 was identified as the first physiological inhibitor of CATSPER1 processing.
  • SPINK3 blocks capacitation-induced CATSPER1 cleavage, maintaining a subpopulation of sperm with intact CatSper channels.
  • SPINK3 stabilizes sperm membrane organization and delays cholesterol efflux, localizing to the principal piece membrane.

Conclusions:

  • SPINK3 is a multifunctional regulator of sperm capacitation.
  • SPINK3 plays a critical role in shaping sperm subpopulations within the female reproductive tract.
  • SPINK3's inhibition of CATSPER1 processing is key to preserving sperm function and fertility.