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Updated: Oct 15, 2025

Functional Assessment of Kinesin-7 CENP-E in Spermatocytes Using In Vivo Inhibition, Immunofluorescence and Flow Cytometry
Published on: December 28, 2021
Cyclin-dependent kinase 7 is essential for spermatogenesis by regulating retinoic acid signaling pathways and the
Xu Chen1, Yan Li1, Haiqian Dai1
1State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.
Abstract:
Spermatogenesis is a complex process that requires precise regulation. Phosphorylation plays a role in spermatogenesis by regulating protein structure and activity. This study focused on cyclin-dependent kinase 7 (CDK7), and explored its function and molecular mechanisms in spermatogenesis in vitro in a cell line and in vivo in a mouse model. Inhibition of CDK7 activity affected spermatogonia proliferation and differentiation, and we found that CDK7 regulates retinoic acid (RA)-mediated c-KIT expression to play a role in spermatogonia. Then, we demonstrated that inhibition of CDK7 affected meiosis initiation, DNA repair, and synaptonemal complex formation in meiosis progression, and CDK7 played this role by regulating RA-mediated STRA8 and REC8 signaling pathways. Moreover, inhibition of CDK7 impacted spermatid differentiation and resulted in decreased counts, decreased motility, and increased head deformity of sperm. We demonstrated that CDK7 affects germ cell apoptosis and sperm motility by activating STAT3 and that STAT3 further regulates Cortactin expression to influence the nuclear elongation, chromatin condensation, and acrosome formation of sperm. Additionally, EP300 was identified as another potential target phosphorylated by CDK7 that participates in chromatin condensation. Our results demonstrated the important role of CDK7 in all key aspects of spermatogenesis, potentially providing an effective target for clinical diagnosis and pathogenesis.
Insights
Cyclin-dependent kinase 7 (CDK7) is crucial for spermatogenesis, regulating germ cell development, meiosis, and sperm formation. CDK7 inhibition impairs sperm production and quality, highlighting its role in male fertility.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Cellular Signaling
Background:
- Spermatogenesis is a complex, highly regulated process essential for male fertility.
- Protein phosphorylation is a key regulatory mechanism in spermatogenesis.
- Cyclin-dependent kinase 7 (CDK7) is implicated in cell cycle control but its specific role in spermatogenesis is not fully understood.
Purpose of the Study:
- To investigate the function and molecular mechanisms of CDK7 in spermatogenesis.
- To explore CDK7's role in regulating germ cell proliferation, differentiation, meiosis, and sperm formation.
Main Methods:
- In vitro studies using a cell line and in vivo studies using a mouse model.
- Inhibition of CDK7 activity to assess its effects on spermatogenesis.
- Analysis of key molecular pathways including retinoic acid (RA)-mediated signaling, STAT3 activation, and EP300 phosphorylation.
Main Results:
- CDK7 inhibition disrupted spermatogonia proliferation and differentiation, affecting RA-mediated c-KIT expression.
- CDK7 regulates meiosis initiation, DNA repair, and synaptonemal complex formation via RA-mediated STRA8 and REC8 pathways.
- CDK7 inhibition led to impaired spermatid differentiation, reduced sperm counts, decreased motility, and increased head deformities, partly through STAT3 and Cortactin.
- EP300 was identified as a CDK7 target involved in chromatin condensation.
Conclusions:
- CDK7 plays a critical role in multiple stages of spermatogenesis, from germ cell development to sperm maturation.
- CDK7 regulates key signaling pathways essential for successful meiosis and sperm formation.
- CDK7 represents a potential therapeutic target for male infertility and related pathogenesis.
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