ABSTRACT
Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.
Subject(s)
Humans , Male , Asthenozoospermia/pathology , Dyneins/genetics , Homozygote , Microtubule-Associated Proteins , Mutation , Mutation, Missense , Sperm Tail/metabolismABSTRACT
Estudiar el efecto del tratamiento con ácido fólico y zinc, en pacientes masculinos subfértiles, con diagnóstico de astenospermia, oligospermia y/o teratospermia. Estudio prospectivo y descriptivo. Se administró tratamiento con ácido fólico (55 mg) y zinc (550 mg) diarios, por un período de 90 días, a pacientes con alteración de la motilidad, concentración y/o morfología espermática. Servicio de Fertilidad. Maternidad Concepción Palacios . Caracas. Después de 90 días de tratamiento, la motilidad total aumento de 44,37 por ciento a 55,22 por ciento, (P=,0002). Las formas espermáticas normales pasaron de 54,11 por ciento a 55,46 por ciento (P=,0001) y las formas anormales disminuyeron e 44,29 por ciento a 4,25 (P=,0001). El tratamiento con ácido fólico y zinc, mejora significativamente la motilidad total y la morfología espermática, en el hombre sub-fértil.