Journal of assisted reproduction and genetics · 2025
Identification of nonfunctional CABS1 causing fertilization failure and male infertility in humans: a case report.
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Huang Yilian, Wang Yize, Li Lou, Gong Fei, Lin Ge, Dai Jing
Аннотация
PURPOSE: This study aimed to identify new genes associated with total fertilization failure (TFF) by intracytoplasmic sperm injection (ICSI).
METHODS: Whole-exome sequencing (WES) was performed on a patient presenting with TFF by ICSI. To assess the spermatozoa's morphology and ultrastructure, hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) were employed. Furthermore, immunofluorescence staining (IF) and western blot (WB) techniques were utilized to investigate the alterations in expression and localization of CABS1 following the transfection of two mutant plasmids. Co-immunoprecipitation (Co-IP) was conducted to investigate in interaction of wild-type/mutant CABS1 with another perinuclear theca protein ACTL9. IF was conducted on spermatozoa from the patient to detect the expression levels of CABS1 and PLCζ.
RESULTS: Homozygous mutations in CABS1 were identified in a patient with TFF after ICSI. A high proportion of spermatozoa collected from this man exhibited abnormal morphology and low motility. TEM revealed an absence of the acrosome in the spermatozoa. In vitro experiments have demonstrated that the nonsense mutation in CABS1 leads to truncation of the protein and a reduction in its interaction with ACTL9. IF analysis of spermatozoa from the patient showed a weakened and a diffuse signal for CABS1, along with abnormal localization of the sperm-borne oocyte activation factor PLCζ, ultimately leading to TFF.
CONCLUSION: Our results suggest that CABS1 may be crucial for acrosome formation and the localization of PLCζ. Mutations in CABS1 may lead to teratozoospermia, TFF, and male infertility.
METHODS: Whole-exome sequencing (WES) was performed on a patient presenting with TFF by ICSI. To assess the spermatozoa's morphology and ultrastructure, hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) were employed. Furthermore, immunofluorescence staining (IF) and western blot (WB) techniques were utilized to investigate the alterations in expression and localization of CABS1 following the transfection of two mutant plasmids. Co-immunoprecipitation (Co-IP) was conducted to investigate in interaction of wild-type/mutant CABS1 with another perinuclear theca protein ACTL9. IF was conducted on spermatozoa from the patient to detect the expression levels of CABS1 and PLCζ.
RESULTS: Homozygous mutations in CABS1 were identified in a patient with TFF after ICSI. A high proportion of spermatozoa collected from this man exhibited abnormal morphology and low motility. TEM revealed an absence of the acrosome in the spermatozoa. In vitro experiments have demonstrated that the nonsense mutation in CABS1 leads to truncation of the protein and a reduction in its interaction with ACTL9. IF analysis of spermatozoa from the patient showed a weakened and a diffuse signal for CABS1, along with abnormal localization of the sperm-borne oocyte activation factor PLCζ, ultimately leading to TFF.
CONCLUSION: Our results suggest that CABS1 may be crucial for acrosome formation and the localization of PLCζ. Mutations in CABS1 may lead to teratozoospermia, TFF, and male infertility.