IQUB deficiency causes male infertility by affecting the activity of p-ERK1/2/RSPH3

AbstractSTUDY QUESTIONCan new genetic factors responsible for male infertility be identified, especially for those characterized by asthenospermia despite normal sperm morphology?SUMMARY ANSWERWe identified the novel pathogenetic gene IQ motif and ubiquitin-like domain-containing (IQUB) as responsible for male infertility characterized by asthenospermia, involving sperm radial spoke defects.WHAT IS KNOWN ALREADYTo date, only a few genes have been found to be responsible for asthenospermia with normal sperm morphology.Iqub, encoding the IQUB protein, is highly and specifically expressed in murine testes and interacts with the proteins radial spoke head 3 (RSPH3), CEP295 N-terminal like (CEP295NL or DDC8), glutathione S-transferase mu 1 (GSTM1) and outer dense fiber of sperm tails 1 (ODF1) in the yeast two-hybrid system.STUDY DESIGN, SIZE, DURATIONTheIQUB variant was identified by whole-exome sequencing in a cohort of 126 male infertility patients with typical asthenospermia recruited between 2015 and 2020. Knockout (KO) and knockin (KI) mouse models, scanning and transmission electron microscopy (TEM), and other functional assays were performed, between 2019 and 2021.PARTICIPANTS/MATERIALS, SETTING, METHODSTheIQUB variant was identified by whole-exome sequencing and confirmed by Sanger sequencing.Iqub KO and KI mice were constructed to mimic the phenotype of the affected individual. After recapitulating the phenotype of human male infertility, scanning and TEM were performed t...
Source: Human Reproduction - Category: Reproduction Medicine Source Type: research