Defects in efferent duct multiciliogenesis underlie male infertility in GEMC1-, MCIDAS- or CCNO-deficient mice

Berta Terré, Michael Lewis, Gabriel Gil-Gómez, Zhiyuan Han, Hao Lu, Mònica Aguilera, Neus Prats, Sudipto Roy, Haotian Zhao, Travis H. Stracker

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

GEMC1 and MCIDAS are geminin family proteins that transcriptionally activate E2F4/5-target genes during multiciliogenesis, including Foxj1 and Ccno. Malemice 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 rete testes, spermagglutinations 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.

Original languageEnglish (US)
Article numberdev162628
JournalDevelopment (Cambridge)
Volume146
Issue number8
DOIs
StatePublished - Apr 15 2019

Fingerprint

Epididymis
Male Infertility
Spermatozoa
Geminin
Rete Testis
Seminiferous Epithelium
Azoospermia
Seminiferous Tubules
Cilia
Genes
Dilatation
Phenotype
Mutation
Proteins
Ciliopathies

Keywords

  • Ccno
  • Efferent ducts
  • Fertility
  • Gemc1
  • Mcidas
  • Multiciliated cells
  • P73
  • Testes
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Terré, B., Lewis, M., Gil-Gómez, G., Han, Z., Lu, H., Aguilera, M., ... Stracker, T. H. (2019). Defects in efferent duct multiciliogenesis underlie male infertility in GEMC1-, MCIDAS- or CCNO-deficient mice. Development (Cambridge), 146(8), [dev162628]. https://doi.org/10.1242/dev.162628

Defects in efferent duct multiciliogenesis underlie male infertility in GEMC1-, MCIDAS- or CCNO-deficient mice. / Terré, Berta; Lewis, Michael; Gil-Gómez, Gabriel; Han, Zhiyuan; Lu, Hao; Aguilera, Mònica; Prats, Neus; Roy, Sudipto; Zhao, Haotian; Stracker, Travis H.

In: Development (Cambridge), Vol. 146, No. 8, dev162628, 15.04.2019.

Research output: Contribution to journalArticle

Terré, B, Lewis, M, Gil-Gómez, G, Han, Z, Lu, H, Aguilera, M, Prats, N, Roy, S, Zhao, H & Stracker, TH 2019, 'Defects in efferent duct multiciliogenesis underlie male infertility in GEMC1-, MCIDAS- or CCNO-deficient mice', Development (Cambridge), vol. 146, no. 8, dev162628. https://doi.org/10.1242/dev.162628
Terré, Berta ; Lewis, Michael ; Gil-Gómez, Gabriel ; Han, Zhiyuan ; Lu, Hao ; Aguilera, Mònica ; Prats, Neus ; Roy, Sudipto ; Zhao, Haotian ; Stracker, Travis H. / Defects in efferent duct multiciliogenesis underlie male infertility in GEMC1-, MCIDAS- or CCNO-deficient mice. In: Development (Cambridge). 2019 ; Vol. 146, No. 8.
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