SEPT14 Mutations and Teratozoospermia: Genetic Effects on Sperm Head Morphology and DNA Integrity
Abstract
:1. Introduction
1.1. Male Infertility and Sperm DNA Damage
1.2. Septins
1.3. SEPT14
2. Materials and Methods
2.1. Participants and Semen Analysis
2.2. Sperm Genomic DNA Extraction, Polymerase Chain Reaction, and Sequencing
2.3. Transmission Electron Microscopy
2.4. Toluidine Blue Staining
2.5. Comet Assay
2.6. Cloning, Transfection, and Immunofluorescence Staining
2.7. Statistical Analysis
3. Results
3.1. Two Novel Missense Mutations in the SEPT14 Gene
3.2. Severely Malformed Heads and Diminished Chromatin Integrity in Sperm with SEPT14 Mutations
3.3. DNA Integrity in Sperm with SEPT14 Mutations
3.4. SEPT14 Mutations Damage the Forming Ability of the Filamentous Structure
4. Discussion
4.1. SEPTs and Sperm DNA Damage
4.2. Sperm DNA Damage and ART
5. Conclusions
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Nucleotide Sequence/Amino Acid Variation | ||||||
---|---|---|---|---|---|---|
c.367G>A/p.Ala123Thr | c.998T>C/p.Ile333Thr | |||||
Ratio | Patients: 3/254; Controls: 0/116 | Patients: 3/254; Controls: 0/116 | ||||
Exon | 4 | 9 | ||||
Case No. | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 |
Clinical feature | Oligoteratozoospermia | Teratozoospermia | Teratozoospermia | Teratozoospermia | Teratozoospermia | Teratozoospermia |
Abnormal morphology (%) (Krueger criteria) | 90 | 88 | 95 | 91 | 90 | 95 |
Head defect (%) | 91 | 83 | 91 | 88 | 93 | 94 |
Neck defect (%) | 1 | 9 | 3 | 9 | 4 | 3 |
Tail defect (%) | 9 | 11 | 10 | 11 | 5 | 18 |
Immature (%) | 11 | 13 | 1 | 3 | 3 | 5 |
Sperm concentration (106/ml) (>15 × 106/mL) | 13 | 145 | 70 | 28 | 68 | 20 |
Progressive motility (%) (>32%) | 49 | 55 | 37 | 48 | 54 | 45 |
Non-progressive motility (%) | 15 | 11 | 16 | 17 | 14 | 30 |
Karyotype | 46, XY | 46, XY | 46, XY | 46, XY | 46, XY | 46, XY |
Age (years) | 31 | 39 | 35 | 32 | 35 | 38 |
Cigarette smoking, alcohol consumption, genital disease | No | No | No | No | No | No |
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Wang, Y.-Y.; Lai, T.-H.; Chen, M.-F.; Lee, H.-L.; Kuo, P.-L.; Lin, Y.-H. SEPT14 Mutations and Teratozoospermia: Genetic Effects on Sperm Head Morphology and DNA Integrity. J. Clin. Med. 2019, 8, 1297. https://doi.org/10.3390/jcm8091297
Wang Y-Y, Lai T-H, Chen M-F, Lee H-L, Kuo P-L, Lin Y-H. SEPT14 Mutations and Teratozoospermia: Genetic Effects on Sperm Head Morphology and DNA Integrity. Journal of Clinical Medicine. 2019; 8(9):1297. https://doi.org/10.3390/jcm8091297
Chicago/Turabian StyleWang, Ya-Yun, Tsung-Hsuan Lai, Mei-Feng Chen, Hui-Ling Lee, Pao-Lin Kuo, and Ying-Hung Lin. 2019. "SEPT14 Mutations and Teratozoospermia: Genetic Effects on Sperm Head Morphology and DNA Integrity" Journal of Clinical Medicine 8, no. 9: 1297. https://doi.org/10.3390/jcm8091297