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Techniques for Imaging Ca2+ Signaling in Human Sperm
Published on: June 16, 2010
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Isoform-specific GSK3A activity is negatively correlated with human sperm motility
M J Freitas1, J V Silva1,2,3, C Brothag4
1Signal Transduction Laboratory, Institute for Research in Biomedicine-iBiMED, Medical Sciences Department, University of Aveiro, Aveiro, Portugal.
Molecular Human Reproduction
|March 3, 2019
Summary
Glycogen synthase kinase 3 alpha (GSK3A) inhibition positively correlates with human sperm motility, suggesting its isoform-specific role in male fertility. This finding highlights GSK3A as a potential target for male contraceptive development.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Sperm Physiology
Background:
- Glycogen synthase kinase 3 (GSK3) activity is inversely related to sperm motility in mice and bovines.
- Previous studies indicated male infertility in mice with GSK3A gene disruption, while GSK3B disruption did not affect fertility.
- The specific role of GSK3 isoforms in human sperm motility remained unestablished.
Purpose of the Study:
- To investigate the isoform-specific function of GSK3 in human sperm motility.
- To correlate GSK3 expression and activity with human sperm motility profiles.
- To identify testicular and sperm GSK3 interactomes for further analysis.
Main Methods:
- Analysis of normospermic and asthenozoospermic human sperm samples.
- Correlation of GSK3 expression and activity with sperm motility parameters.
- Yeast two-hybrid screening and coimmunoprecipitation for interactome identification.
- In-silico analysis of the GSK3 interactome.
Main Results:
- Inhibited GSK3A (phosphorylated at serine) showed a significant positive correlation (r = 0.822, P = 0.023) with progressive human sperm motility.
- Inhibited GSK3B did not show a significant correlation with sperm motility (r = 0.577, P = 0.175).
- In-silico analysis revealed significant involvement of GSK3 interactors in sperm motility-related functions.
Conclusions:
- Human sperm motility is dependent on the isoform-specific functions of GSK3A.
- GSK3 protein-protein interactions are crucial for sperm motility.
- GSK3 isoforms represent potential targets for male contraceptive strategies modulating sperm motility.
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