Voltage-dependent anion channel isoform 3 as a potential male contraceptive drug target

Future Med Chem. 2019 Apr;11(8):857-867. doi: 10.4155/fmc-2018-0328. Epub 2019 Apr 18.

Abstract

Voltage-dependent anion channel isoform 3 (VDAC3), a channel in the mitochondrial outer membrane, has been suggested to play a role in the regulation of ATP transport and Ca2+ homeostasis. These processes are regarded as important for spermatozoa motility. Accordingly, in previous years, mutations in the VDAC3-encoding gene were detected in spermatozoa with low motility from infertile patients. Therefore, it can be assumed that these mutations would cause alteration of the structure and/or charge of the VDAC3 channel. The review is focused on current knowledge about contribution of VDAC3 activity to human spermatozoa motility and morphology. We also discuss the possibility of designing new molecules that could specifically block the VDAC3 channel and consequently act as male contraceptives.

Keywords: VDAC3; male contraceptives; spermatozoa.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Contraceptive Agents, Male / chemistry
  • Contraceptive Agents, Male / pharmacology*
  • Drug Design
  • Drug Discovery / methods
  • Humans
  • Male
  • Mitochondrial Membrane Transport Proteins / antagonists & inhibitors*
  • Mitochondrial Membrane Transport Proteins / metabolism*
  • Sperm Motility / drug effects
  • Spermatozoa / cytology
  • Spermatozoa / drug effects*
  • Spermatozoa / metabolism
  • Voltage-Dependent Anion Channels / antagonists & inhibitors*
  • Voltage-Dependent Anion Channels / metabolism*

Substances

  • Contraceptive Agents, Male
  • Mitochondrial Membrane Transport Proteins
  • VDAC3 protein, human
  • Voltage-Dependent Anion Channels