Missense mutation in DNAJB13 gene correlated with male fertility in asthenozoospermia

Background The most common type of male infertility is asthenospermia. We cloned DnaJ heat shock protein family member B13 (Dnajb13/DNAJB13), a type II HSP40 family member that is highly expressed in the testis. DNAJB13 plays a crucial role in sperm flagellar function. Objectives The aim of this study was to investigate whether a correlation exists between DNAJB13 and low sperm motility in infertile men. Materials and methods In the present study, we performed a mutation screening of the DNAJB13 gene in 92 idiopathic asthenozoospermia patients and 200 men with normal fertility. Additionally, we used immunoelectron microscopy, co-immunoprecipitation, mass spectrometric detection, indirect immunofluorescence assay, transmission electron microscopy studies, isobaric tags for relative and absolute quantitation, and multiple reaction monitoring studies to analyze changes in DNAJB13 protein. Results A novel c.106T>C mutation of DNAJB13 was present in nearly 10% (9/92) of idiopathic asthenozoospermia patients and was absent in 200 fertile men. A computer-assisted sperm analyzer and transmission electron microscopy analysis using samples from 9 patients with DNAJB13 mutations demonstrated that most spermatozoa were immotile due to sperm tail defects. Multiple reaction monitoring results indicated that DNAJB13 protein levels were reduced after gene mutation. We achieved a pregnancy rate of 100% in 8 patients with DNAJB13 mutations using ICSI. Discussion and conclusion The DNAJB13 heterozygous variant may affect fertility. ICSI can help these patients with low fertility to father children.