Sperm defects in primary ciliary dyskinesia and related causes of male infertility

Cell Mol Life Sci. 2020 Jun;77(11):2029-2048. doi: 10.1007/s00018-019-03389-7. Epub 2019 Nov 28.

Abstract

The core axoneme structure of both the motile cilium and sperm tail has the same ultrastructural 9 + 2 microtubular arrangement. Thus, it can be expected that genetic defects in motile cilia also have an effect on sperm tail formation. However, recent studies in human patients, animal models and model organisms have indicated that there are differences in components of specific structures within the cilia and sperm tail axonemes. Primary ciliary dyskinesia (PCD) is a genetic disease with symptoms caused by malfunction of motile cilia such as chronic nasal discharge, ear, nose and chest infections and pulmonary disease (bronchiectasis). Half of the patients also have situs inversus and in many cases male infertility has been reported. PCD genes have a role in motile cilia biogenesis, structure and function. To date mutations in over 40 genes have been identified cause PCD, but the exact effect of these mutations on spermatogenesis is poorly understood. Furthermore, mutations in several additional axonemal genes have recently been identified to cause a sperm-specific phenotype, termed multiple morphological abnormalities of the sperm flagella (MMAF). In this review, we discuss the association of PCD genes and other axonemal genes with male infertility, drawing particular attention to possible differences between their functions in motile cilia and sperm tails.

Keywords: Axoneme; Cilia; Dynein; Infertility; MMAF; Motility; PCD; Sperm tail.

Publication types

  • Review

MeSH terms

  • Animals
  • Cilia / genetics
  • Cilia / metabolism
  • Cilia / pathology
  • Ciliary Motility Disorders / complications*
  • Ciliary Motility Disorders / genetics
  • Ciliary Motility Disorders / pathology
  • Humans
  • Infertility, Male / etiology*
  • Infertility, Male / genetics
  • Infertility, Male / pathology
  • Male
  • Mutation
  • Spermatozoa / metabolism
  • Spermatozoa / pathology*