Defects in efferent duct multiciliogenesis underlie male infertility in GEMC1, MCIDAS or CCNO deficient mice
-
- Berta Terré
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain
-
- Michael Lewis
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain
-
- Gabriel Gil-Gómez
- Apoptosis Signalling Group, IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain
-
- Zhiyuan Han
- Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York, USA
-
- Lu Hao
- Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore
-
- Mònica Aguilera
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain
-
- Neus Prats
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain
-
- Sudipto Roy
- Institute of Molecular and Cell Biology, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore
-
- Haotian Zhao
- Department of Biomedical Sciences, New York Institute of Technology College of Osteopathic Medicine, Old Westbury, New York, USA
-
- Travis H. Stracker
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona 08028, Spain
抄録
<jats:p>GEMC1 and MCIDAS are Geminin family proteins that transcriptionally activate E2F4/5-target genes during multiciliogenesis, including FoxJ1 and Ccno. Male mice lacking Gemc1, Mcidas or Ccno were found to be infertile, but the origin of this defect has remained unclear. Here we show that all three genes are necessary for the generation of functional multiciliated cells in the efferent ducts that are required for spermatozoa to enter the epididymis. In mice mutant for Gemc1, Mcidas or Ccno, we observed a similar spectrum of phenotypes, including thinning of the seminiferous tubule epithelia, dilation of the rete testes, sperm agglutinations in the efferent ducts and lack of spermatozoa in the epididymis (azoospermia). These data suggest that defective efferent duct development is the dominant cause of male infertility in these mouse models and this likely extends to patients with the ciliopathy Reduced Generation of Multiple Motile Cilia with mutations in MCIDAS and CCNO.</jats:p>
収録刊行物
-
- Development
-
Development 2019-01-01
The Company of Biologists