KIF3B gene silent variant leading to sperm morphology and motility defects and male infertility

Abstract

Sperm structural and functional defects are leading causes of male infertility. Patients with immotile sperm disorders suffer from axoneme failure and show a significant reduction in sperm count. The kinesin family member 3B (KIF3B) is one of the genes involved in the proper formation of sperm with a critical role in intraflagellar and intramanchette transport. A part of exon 2 and exons 3–5 of the KIF3B encodes a protein coiled-coil domain that interacts with IFT20 from the IFT protein complex. In the present study, the coding region of KIF3B coiled-coil domain was assessed in 88 oligoasthenoteratozoospermic patients, and the protein expression was evaluated in the mature spermatozoa of the case and control groups using immunocytochemistry and western blotting. According to the results, there was no genetic variation in the exons 3–5 of the KIF3B, but a new A > T variant was identified within the exon 2 in 30 patients, where nothing was detected in the control group. In contrast to healthy individuals, significantly reduced protein expression was observable in oligoasthenoteratozoospermic (OAT) patients carrying variation where protein organization was disarranged, especially in the principal piece and midpiece of the sperm tail. Besides, the protein expression level was lower in the patients’ samples compared to that of the control group. According to the results of the present study the NM_004798.3:c.1032A > T, p.Pro344 = variant; which has been recently submitted to the Clinvar database; although synonymous, causes alterations in the transcription factor binding site, exon skipping, and also exonic splicing enhancer-binding site. Therefore, KIF3B can play an important role in spermatogenesis and the related protein reduction can cause male infertility.

Identifying Candidate Genes for Litter Size and Three Morphological Traits in Youzhou Dark Goats Based on Genome-Wide SNP Markers

“…In addition to the genes related to early domestication, a panel of interesting genes associated with other economic traits was also revealed. These genes were previously reported in goats, sheep and other species, showing correlations with spermatogenesis and sperm motility (KIF3B, KIF17, KIAA0825 and TNFRSF21) [53][54][55][56], growth and development (TNPO2, IFT80, UCP2, UCP3, GHRHR, SIM1, CCM2L, CTNNA3 and CTNNA1) [57][58][59][60][61][62][63][64], fat deposition (ACSF3 and FGGY) [65,66], chicken heat tolerance (TSHR and SUGCT) [67], highaltitude hypoxia adaptation (CHL1) [68], milk composition (GHRHR) [69], milk flavour (ACSF3) [70], carcass traits (GHRHR) [71] and hair follicle morphogenesis (GLI2) [72]. The iHS and ROH methods both detected some genes, but each method found additional genes not detected by the other.…”

Identification of bi-allelic KIF9 loss-of-function variants contributing to asthenospermia and male infertility in two Chinese families

“…Another member of the kinesin superfamily, KIF3B, has also been found to be mutated in some cases of male infertility ( 33 ). The function of KIF3B has been studied in the context of intracellular transport and spermatogenesis in many species ( 34 – 36 ).…”

“…The function of KIF3B has been studied in the context of intracellular transport and spermatogenesis in many species ( 34 – 36 ). A human A>T variant in OAT patients was linked to decreased KIF3B expression resulting in impaired male fertility ( 33 ). Other kinesins have also been reported to influence spermatogenesis by regulating IFT and intramanchette transport processes ( 37 – 39 ).…”

Epigenetic Alterations in Cryopreserved Human Spermatozoa: Suspected Potential Functional Defects

“…Spermatozoa development requires the movement of microtubules to drive the assembly of the flagella on the spermatozoa head. For example, KIF3A and KIF3B may be involved in the formation of spermatozoa acrosomes, and silencing KIF3B can lead to defects in spermatozoa motility and morphology [52][53][54]. In turn, KIF11 plays an important role in the travel of the spindle during spermatogonia meiosis [55].…”