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Updated: Oct 9, 2025
Flow Cytometric Analysis of Biomarkers for Detecting Human Sperm Functional Defects
Published on: April 21, 2022
[Homozygous CFAP65 mutation induces multiple morphological abnormalities of sperm flagella: A preliminary genetic
Chuan Jiang1, Xue-Guang Zhang1, Xiang Wang1
1Joint Laboratory of Reproductive Medicine / Key Laboratory of the Ministry of Education for Birth Defects and Related Women and Children's Diseases, West China Second Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
Objective:
To search for the possible pathogenic genes for multiple morphological anomalies of sperm flagella (MMAF).
Methods:
We performed whole exome sequencing (WES) of a typical case of MMAF and analyzed its possible pathogenic genes. We examined the semen sample from the patient and identified the ultrastructural characteristics of the sperm flagella under the scanning electron and transmission electron microscopes, and analyzed the expression pattern of cilia and flagela-associated protein 65 (CFAP65) in spermatogenesis by immunofluorescence assay.
Results:
The MMAF patient was found with a homozygous pathogenic mutation of the CFAP65 gene c.2675G>A(p.Trp892*). Scanning electron microscopy showed that the sperm of the patient had typical characteristics of MMAF, that is, without tails or with folded tails, curly tails, short tails or irregular tails. Transmission electron microscopy revealed the loss and disorder of the "9+2" structure in the sperm flagellum, with abnormal assembly of the fibrous sheath, accompanied by loss of central microtubules and dynamin arms. Cellular immunofluorescence assay suggested that the CFAP65 gene was expressed at all levels of mouse germ cells.
Conclusions:
The CFAP65 gene is involved in the assembly of the sperm flagellum structure, and its mutation can cause the phenotype of MMAF, leading to male infertility.
Insights
A mutation in the cilia and flagella-associated protein 65 (CFAP65) gene causes multiple morphological anomalies of sperm flagella (MMAF). This genetic defect disrupts sperm structure, leading to male infertility.
Area of Science:
- Genetics
- Reproductive Biology
- Cell Biology
Background:
- Multiple Morphological Anomalies of Sperm Flagella (MMAF) is a condition characterized by severe sperm defects.
- Identifying the genetic basis of MMAF is crucial for understanding male infertility.
Purpose of the Study:
- To identify pathogenic genes responsible for MMAF.
- To investigate the role of CFAP65 in sperm flagellar assembly.
Main Methods:
- Whole exome sequencing (WES) was performed on an MMAF patient.
- Sperm ultrastructure was analyzed using scanning and transmission electron microscopy.
- Cilia and flagella-associated protein 65 (CFAP65) expression was assessed via immunofluorescence.
Main Results:
- A homozygous pathogenic mutation (c.2675G>A) in the CFAP65 gene was identified in the MMAF patient.
- Sperm analysis revealed typical MMAF characteristics, including absent or malformed flagella.
- Electron microscopy showed disruption of the sperm flagellar "9+2" structure and associated components.
Conclusions:
- The CFAP65 gene plays a critical role in sperm flagellar structure assembly.
- Mutations in CFAP65 can cause MMAF and result in male infertility.
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