Affiliation:
1. Department of General Pediatrics, University Hospital Muenster, Muenster 48149, Germany
2. Department of Clinical Andrology, Centre of Reproductive Medicine and Andrology, University Hospital Muenster, Muenster 48149, Germany
Abstract
Abstract
Motile cilia line the efferent ducts of the mammalian male reproductive tract. Several recent mouse studies have demonstrated that a reduced generation of multiple motile cilia in efferent ducts is associated with obstructive oligozoospermia and fertility issues. However, the sole impact of efferent duct cilia dysmotility on male infertility has not been studied so far either in mice or human. Using video microscopy, histological- and ultrastructural analyses, we examined male reproductive tracts of mice deficient for the axonemal motor protein DNAH5: this defect exclusively disrupts the outer dynein arm (ODA) composition of motile cilia but not the ODA composition and motility of sperm flagella. These mice have immotile efferent duct cilia that lack ODAs, which are essential for ciliary beat generation. Furthermore, they show accumulation of sperm in the efferent duct. Notably, the ultrastructure and motility of sperm from these males are unaffected. Likewise, human individuals with loss-of-function DNAH5 mutations present with reduced sperm count in the ejaculate (oligozoospermia) and dilatations of the epididymal head but normal sperm motility, similar to DNAH5 deficient mice. The findings of this translational study demonstrate, in both mice and men, that efferent duct ciliary motility is important for male reproductive fitness and uncovers a novel pathomechanism distinct from primary defects of sperm motility (asthenozoospermia). If future work can identify environmental factors or defects in genes other than DNAH5 that cause efferent duct cilia dysmotility, this will help unravel other causes of oligozoospermia and may influence future practices in genetic and fertility counseling as well as ART.
Funder
Deutsche Forschungsgemeinschaft
Interdisziplinaeres Zentrum für Klinische Forschung Muenster
the European Commission (BESTCILIA
LYSOCIL
Registry Warehouse
COST action BEAT-PCD, the Schroeder Stiftung, Kindness for Kids
Eva Luise und Horst Köhler Stiftung
Care-for Rare Foundation
Publisher
Oxford University Press (OUP)
Subject
Cell Biology,Developmental Biology,Obstetrics and Gynaecology,Genetics,Molecular Biology,Embryology,Reproductive Medicine
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