期刊
DEVELOPMENT
卷 146, 期 8, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.162628
关键词
Fertility; Multiciliated cells; Testes; Efferent ducts; GEMC1; MCIDAS; CCNO; P73; Transcription
资金
- Ministerio de Economia y Competitividad (MINECO) [BFU2015-68354/GENPATH]
- Ministerio de Economia y Competitividad (MINECO) (FEDER)
- Centres of Excellence Severo Ochoa award
- CERCA Programme
- Severo Ochoa FPI fellowships (MINECO)
- Instituto de Salud Carlos III [PI13/00864]
- European Regional Development Fund
- New York Institute of Technology
- National Cancer Institute [R01CA220551]
- Agency for Science, Technology and Research of Singapore
- Ministerio de Economia y Competitividad (MINECO) (GINDATA)
GEMC1 and MCIDAS are geminin family proteins that transcriptionally activate E2F4/5-target genes during multiciliogenesis, including Foxj1 and Ccno. Male mice that lacked 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 that are mutant for Gemc1, Mcidas or Ccno, we observed a similar spectrum of phenotypes, including thinning of the seminiferous tubule epithelia, dilation of the rate 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 individuals with the ciliopathy reduced generation of multiple motile cilia with mutations in MCIDAS and CCNO.
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