TY - JOUR
T1 - Sperm defects in primary ciliary dyskinesia and related causes of male infertility
AU - Sironen, Anu
AU - Shoemark, Amelia
AU - Patel, Mitali
AU - Loebinger, Michael R.
AU - Mitchison, Hannah M.
N1 - Funding for this research was provided by: H2020 Marie Skłodowska-Curie Actions (800556); Great Ormond Street Hospital Charity (V2217); National Institute for Health Research (V1299)
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
KW - Axoneme
KW - Cilia
KW - Dynein
KW - Infertility
KW - MMAF
KW - Motility
KW - PCD
KW - Sperm tail
UR - http://www.scopus.com/inward/record.url?scp=85075680256&partnerID=8YFLogxK
U2 - 10.1007/s00018-019-03389-7
DO - 10.1007/s00018-019-03389-7
M3 - Review article
C2 - 31781811
VL - 77
SP - 2029
EP - 2048
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
SN - 1420-682X
IS - 11
ER -