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Updated: Jun 29, 2025
Measuring Sperm Guidance and Motility within the Caenorhabditis elegans Hermaphrodite Reproductive Tract
Published on: June 6, 2019
Forkhead-associated phosphopeptide binding domain 1 (FHAD1) deficiency impaired murine sperm motility
Xi Zhang1,2, Jiangyang Xue2,3, Shan Jiang4
1Department of Reproductive Health and Infertility Clinic, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China.
Insights
Genetic knockout of Forkhead-associated phosphopeptide binding domain 1 (FHAD1) in mice revealed its role in male fertility. FHAD1 deficiency impacts sperm motility and increases apoptosis during spermatogenesis.
Area of Science:
- Reproductive Biology
- Molecular Genetics
Background:
- Genetic knockout studies in mice are crucial for understanding gene function in fertility.
- Forkhead-associated phosphopeptide binding domain 1 (FHAD1) possesses a conserved FHA domain, suggesting a role in phospho-threonine binding.
- The specific function of FHAD1 in male fertility is not well understood.
Purpose of the Study:
- To investigate the role of FHAD1 in male fertility using a genetic knockout mouse model.
- To analyze the impact of FHAD1 deficiency on spermatogenesis, sperm parameters, and testicular function.
Main Methods:
- CRISPR/Cas9 technology was employed to generate Fhad1 knockout mice.
- Quantitative PCR (qPCR) assessed gene expression changes.
- Spermatogenesis and fertility were evaluated through histological staining, immunofluorescence, and computer-aided sperm analysis.
- Apoptosis was quantified using TUNEL staining.
Main Results:
- Fhad1 knockout mice showed no significant alterations in fertility or testicular morphology compared to wild-type littermates.
- While testicular structure remained intact, Fhad1 knockout mice exhibited reduced epididymal sperm concentration and motility.
- Increased apoptotic cell death was observed during the initial wave of spermatogenesis in Fhad1 knockout mice.
Conclusions:
- FHAD1 plays a role in male reproductive processes, specifically in meiosis and sperm motility regulation.
- These findings highlight FHAD1 as a potential target for understanding and addressing male infertility.
Background:
Genetic knockout-based studies conducted in mice provide a powerful means of assessing the significance of a gene for fertility. Forkhead-associated phosphopeptide binding domain 1 (FHAD1) contains a conserved FHA domain, that is present in many proteins with phospho-threonine reader activity. How FHAD1 functions in male fertility, however, remains uncertain.
Methods:
Fhad1-/- mice were generated by CRISPR/Cas9-mediated knockout, after which qPCR was used to evaluate changes in gene expression, with subsequent analyses of spermatogenesis and fertility. The testis phenotypes were also examined using immunofluorescence and histological staining, while sperm concentrations and motility were quantified via computer-aided sperm analysis. Cellular apoptosis was assessed using a TUNEL staining assay.
Results:
The Fhad1mice did not exhibit any abnormal changes in fertility or testicular morphology compared to wild-type littermates. Histological analyses confirmed that the testicular morphology of both Fhad1and Fhad1 mice was normal, with both exhibiting intact seminiferous tubules. Relative to Fhad1 mice, however, Fhad1did exhibit reductions in the total and progressive motility of epididymal sperm. Analyses of meiotic division in Fhad1mice also revealed higher levels of apoptotic death during the first wave of spermatogenesis.
Discussion:
The findings suggest that FHAD1 is involved in both meiosis and the modulation of sperm motility.
