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Published on: June 16, 2021
Role of Fyn kinase in oocyte developmental potential
Jinping Luo1, Lynda K McGinnis, William H Kinsey
1Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Abstract:
Fyn kinase is highly expressed in oocytes, with inhibitor and dominant-negative studies suggesting a role in the signal transduction events during egg activation. The purpose of the present investigation was to test the hypothesis that Fyn is required for calcium signalling, meiosis resumption and pronuclear congression using the Fyn-knockout mouse as a model. Accelerated breeding studies revealed that Fyn-null females produced smaller litter sizes at longer intervals and exhibited a rapid decline in pup production with increasing age. Fyn-null females produced a similar number of oocytes, but the frequency of immature oocytes and mature oocytes with spindle chromosome abnormalities was significantly higher than in controls. Fertilised Fyn-null oocytes frequently (24%) failed to undergo pronuclear congression and remained at the one-cell stage. Stimulation with gonadotropins increased the number of oocytes ovulated, but did not overcome the above defects. Fyn-null oocytes overexpressed Yes kinase in an apparent effort to compensate for the loss of Fyn, yet still exhibited an altered pattern of protein tyrosine phosphorylation. In summary, Fyn-null female mice exhibit reduced fertility that appears to result from actin cytoskeletal defects rather than calcium signalling. These defects cause developmental arrest during oocyte maturation and pronuclear congression.
Insights
Fyn kinase deficiency in female mice impairs fertility due to oocyte developmental defects. These Fyn-null mice show reduced litter sizes and oocyte abnormalities, impacting reproductive success.
Area of Science:
- Reproductive Biology
- Cell Signaling
- Molecular Genetics
Background:
- Fyn kinase is crucial for oocyte maturation and egg activation.
- Previous studies suggest Fyn kinase involvement in signal transduction during egg activation.
Purpose of the Study:
- To investigate the role of Fyn kinase in oocyte calcium signaling, meiosis resumption, and pronuclear congression.
- To utilize Fyn-knockout mice to test Fyn's necessity in these reproductive processes.
Main Methods:
- Utilized Fyn-knockout mouse model for reproductive studies.
- Assessed oocyte maturation, spindle chromosome abnormalities, and pronuclear congression.
- Evaluated fertility parameters including litter size and pup production over time.
Main Results:
- Fyn-null females exhibited reduced fertility, smaller litters, and age-related decline in pup production.
- Oocytes from Fyn-null mice showed increased immaturity and spindle chromosome abnormalities.
- Fertilized Fyn-null oocytes frequently failed pronuclear congression, leading to developmental arrest.
Conclusions:
- Fyn kinase is essential for female fertility, primarily due to actin cytoskeletal defects affecting oocyte maturation and pronuclear congression.
- The fertility defects in Fyn-null mice are not primarily due to impaired calcium signaling.
- Fyn deficiency leads to developmental arrest at the oocyte stage, impacting overall reproductive capability.
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