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

Biol Reprod. 2022 Apr 26;106(4):766-774. doi: 10.1093/biolre/ioab226.

Abstract

Sperm structural and functi onal 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 intraflagellar transport 20 (IFT20) from the intraflagellar transport protein complex. In the present study, the coding region of KIF3B coiled-coil domain was assessed in 88 oligoasthenoteratozoospermic (OAT) 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 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 KIF3B gene variation as well as lower protein expression leads to defects in sperm morphology and motility and consequently to male infertility.

Keywords: KIF3B; genetic variant; male infertility; protein expression.

MeSH terms

  • Humans
  • Infertility, Male* / genetics
  • Infertility, Male* / metabolism
  • Kinesins* / genetics
  • Male
  • Proteins / metabolism
  • Sperm Tail
  • Spermatogenesis
  • Spermatozoa* / pathology

Substances

  • KIF3B protein, human
  • Proteins
  • Kinesins