Multiple morphological abnormalities of the flagella (MMAF) represent a severe form of sperm defects leading to asthenozoospermia and male infertility. In this study, we identified a novel homozygous splicing mutation (c.871-4 ACA>A) in the adenylate kinase 7 (AK7) gene by whole-exome sequencing in infertile individuals. Spermatozoa from affected individuals exhibited typical MMAF characteristics, including coiled, bent, short, absent, and irregular flagella. Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella. Immunofluorescence staining confirmed the absence of AK7 protein from the patients' spermatozoa, validating the pathogenic nature of the mutation. This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans, expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.
Humans ; Male ; Sperm Tail/ultrastructure* ; Homozygote ; Consanguinity ; Asthenozoospermia/pathology* ; Infertility, Male/genetics* ; Mutation ; Pakistan ; Adenylate Kinase/genetics* ; Adult ; Pedigree ; RNA Splicing ; Exome Sequencing ; Spermatozoa

Objective: Present study was conducted to investigate in liver of rats from 8-12 weeks old to 20 weeks old, the age dependent changes, carbon tetrachloride mediated changes, and the hepatoprotective effect shown by the seeds of Vitis vinifera L. Method: The hepatoprotective activity was studied by observing the effect of 100 mg/kg dose of ethanolic extract of grape seeds on carbon tetrachloride induced hepatotoxicity in albino rats and results were compared with those of the aged group results. Results: 100 mg/kg b.w. of ethanolic extract of Vitis vinifera seeds produced highly significant decrease in AST, ALT, ALP, bilirubin, albumin levels and significant decrease in the TSP levels compared to the toxic group levels. The levels of AST, ALT, ALP, bilirubin and albumin in aged control rats were found to be significantly higher than the levels in young control animals. MDA levels were slightly higher while GSH levels were lower in aged control rats as compared to young control rats. MDA levels in the toxic group showed highly significant increase compared to the young control levels. Ethanolic extract of seeds of Vitis vinifera significantly lowered the MDA levels. Histopathology results reveal that 100mg/kg/day dose of ethanolic extract of seeds of Vitis vinifera L. cured the hepatic damage to a great extent which was induced by CCl4. Conclusions: Aging leads to the changes in the hepatic structure which are comparable to the changes induced by low doses of a hepatotoxin and the ethanolic extract of seeds of Vitis vinifera L. was effective in bringing about functional improvement of hepatocytes exposed to free radical attack, which was confirmed by biochemical and histological observations.