Acrosomal alkalinization occurs during human sperm capacitation

Area of Science:

• Reproductive Biology
• Cell Physiology

Background:

• Sperm capacitation is crucial for fertilization, involving sperm modifications in the female reproductive tract.
• Capacitation requires increased intracellular calcium and pH, preparing sperm for the acrosome reaction (AR).
• While acrosomal alkalinization triggers AR in mice, its natural occurrence in humans is unclear.

Purpose of the Study:

• To investigate the natural changes in acrosome pH (pHa) during human sperm capacitation.
• To identify the regulatory mechanisms of acrosome alkalinization.

Main Methods:

• Single-cell imaging and image-based flow cytometry were employed to assess pHa.
• Immunolocalization was used to determine the location of V-ATPase.
• Functional assays involved manipulating extracellular ions and enzyme inhibitors.

Main Results:

• Acrosome pH (pHa) progressively increases during human sperm capacitation.
• The V-ATPase, localized to the acrosome, is a key regulator of acrosomal acidity.
• Acrosome alkalinization depends on extracellular bicarbonate and calcium, and involves HCO3--dependent adenylyl cyclase and protein kinase A pathways.

Conclusions:

• Progressive acrosome alkalinization is a natural event during human sperm capacitation.
• V-ATPase regulation plays a significant role in modulating pHa during capacitation.
• Acrosome alkalinization is a critical step preceding the acrosome reaction, essential for successful fertilization.