Search

BackgroundOligoteratoasthenozoospermia (OTA) combines deteriorated quantity, morphology and motility of the sperm, resulting in male factor infertility.MethodsWe used whole genome genotyping and exome sequencing to identify the mutation causing OTA in four men in a consanguineous Bedouin family. We expressed the normal and mutated proteins tagged with c-Myc at the carboxy termini by transfection with pCDNA3.1 plasmid constructs to evaluate the effects on protein stability in HEK293 cells and on the kinetics of actin repolymerisation in retinal pigment epithelium cells. Patients’ sperm samples were visualised by transmission electron microscopy to determine axoneme structures and were stained with fluorescent phalloidin to visualise the fibrillar (F)-actin.ResultsA homozygous missense mutation in Ciliogenesis Associated TTC17 Interacting Protein (CATIP): c. T103A, p. Phe35Ile, a gene encoding a protein important in actin organisation and ciliogenesis, was identified as the causative mutation with a LOD score of 3.25. The mutation reduces the protein stability compared with the normal protein. Furthermore, overexpression of the normal protein, but not the mutated protein, inhibits repolymerisation of actin after disruption with cytochalasin D. A high percentage of spermatozoa axonemes from patients have abnormalities, as well as disturbances in the distribution of F-actin.ConclusionThis is the first report of a recessive mutation in CATIP in humans. The identified mutation may contribute to asthenozoospermia by its involvement in actin polymerisation and on the actin cytoskeleton. A mouse knockout homozygote for CATIP was reported to demonstrate male infertility as the sole phenotype.

The present study investigated the association between oocyte zona pellucida shear modulus (ZPSM) and implantation rate (IR). Ninety-three oocytes collected from 38 in-vitro fertilization patients who underwent intracytoplasmic sperm injection were included in this case–control study. The ZP was modeled as an isotropic compressible hyperelastic material with parameter $$C_{10}$$ C 10 , which represents the ZPSM. Computational methodology was used to calculate the mechanical parameters that govern ZP deformation. Fifty-one developed embryos were transferred and divided into two groups—implanted and not implanted. Multivariate logistic regression analysis was performed to identify the association between ZPSM and IR while controlling for confounders. Maternal age and number of embryos per transfer were significantly associated with implantation. The IR of embryos characterized by $$C_{10}$$ C 10 values in the range of 0.20–0.40 kPa was 66.75%, while outside this range it was 6.70%. This range was significantly associated with implantation (p p = 0.001). The present study suggests that ZPSM may improve the classic embryo selection process with the aim of increasing IR.

Oligoteratoasthenozoospermia (OTA) combines deteriorated quantity, morphology and motility of the sperm, resulting in male factor infertility.We used whole genome genotyping and exome sequencing to identify the mutation causing OTA in four men in a consanguineous Bedouin family. We expressed the normal and mutated proteins tagged with c-Myc at the carboxy termini by transfection with pCDNA3.1 plasmid constructs to evaluate the effects on protein stability in HEK293 cells and on the kinetics of actin repolymerisation in retinal pigment epithelium cells. Patients' sperm samples were visualised by transmission electron microscopy to determine axoneme structures and were stained with fluorescent phalloidin to visualise the fibrillar (F)-actin.A homozygous missense mutation in Ciliogenesis Associated TTC17 Interacting Protein (This is the first report of a recessive mutation in