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Updated: Sep 17, 2025
Flow Cytometric Analysis of Biomarkers for Detecting Human Sperm Functional Defects
Published on: April 21, 2022
Patients with mutations in DNAH2, DNAH6 and DNAH10 causing multiple morphological abnormalities of human sperm
Xueqi Li1, Haibing Yu1, Xiangrong Tang1
1Centre for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University, Chongqing, China; Chongqing Health Centre for Women and Children, Chongqing, China.
Research Questions:
What additional genetic mutations in DNAH2, DNAH6 and DNAH10 are linked to multiple morphological abnormalities of sperm flagella (MMAF), and what are the assisted reproductive outcomes in couples affected by these mutations?
Design:
A cohort of 75 infertile males with MMAF underwent whole-exome sequencing and Sanger sequencing to identify pathogenic mutations. Papanicolaou staining and electron microscopy were employed to evaluate sperm morphology and ultrastructure. Immunofluorescence was performed to characterize ultrastructural abnormalities at the molecular level, and explore the underlying molecular mechanisms by which mutations in DNAH2, DNAH6 and DNAH10 genes lead to MMAF.
Results:
Ten mutations were identified in six unrelated infertile males and were predicted to be pathogenic by bioinformatic tools. Papanicolaou staining and scanning electron microscopy showed that all the male patients harbouring mutations in the DNAH2, DNAH6 and DNAH10 loci displayed severe sperm morphological defects, predominantly characterized by the absence and reduced length of sperm flagella. Transmission electron microscopy (TEM) revealed substantial loss of inner dynein arms and mitochondrial damage, and immunofluorescence data further supported the findings of TEM and indicated a possible interaction between DNAH2 and DNAH10. Moreover, five out of six affected couples achieved a live birth via intracytoplasmic sperm injection (ICSI).
Conclusions:
The data suggest that patients with DNAH2, DNAH6 and DNAH10 mutations causing severe asthenoteratozoospermia can achieve favourable outcomes through ICSI. These findings broaden the spectrum of DNAH2, DNAH6 and DNAH10 mutations, and provide valuable insights for future genetic counselling of infertile males with MMAF.
Insights
New genetic mutations in DNAH2, DNAH6, and DNAH10 are linked to multiple morphological abnormalities of sperm flagella (MMAF). Couples with these mutations achieved successful live births through intracytoplasmic sperm injection (ICSI).
Area of Science:
- Genetics
- Reproductive Biology
- Molecular Biology
Background:
- Multiple morphological abnormalities of sperm flagella (MMAF) is a complex genetic condition affecting male fertility.
- Specific gene mutations, including in DNAH2, DNAH6, and DNAH10, are implicated in MMAF, but the full spectrum of mutations and their impact on reproductive outcomes require further investigation.
Purpose of the Study:
- To identify additional genetic mutations in DNAH2, DNAH6, and DNAH10 associated with MMAF.
- To evaluate the assisted reproductive outcomes in couples where the male partner has MMAF due to these specific gene mutations.
Main Methods:
- Whole-exome and Sanger sequencing were used to identify mutations in a cohort of infertile males with MMAF.
- Sperm morphology and ultrastructure were assessed using Papanicolaou staining and electron microscopy (SEM, TEM).
- Immunofluorescence was employed to investigate molecular mechanisms and potential gene interactions.
Main Results:
- Ten pathogenic mutations in DNAH2, DNAH6, and DNAH10 were identified in six infertile males.
- Patients exhibited severe sperm flagellar defects, including absence and reduced length, along with inner dynein arm loss and mitochondrial damage.
- Five out of six couples achieved live births via intracytoplasmic sperm injection (ICSI).
Conclusions:
- Mutations in DNAH2, DNAH6, and DNAH10 can cause severe asthenoteratozoospermia and MMAF.
- Affected patients can achieve favorable reproductive outcomes with intracytoplasmic sperm injection (ICSI).
- These findings expand the known mutation spectrum for these genes and aid in genetic counseling for male infertility.
