• PMID: 31123254
• Gene Name: DDX5
• Condition: Important for Spermatogenesis, Male infertility
• Association: Associated
• Mutation: Knockout mouse model
• Sex: Male
• Infertility type: Male infertility
• Associated genes: PLZF
• Other associated phenotypes: Important for spermatogenesis, Male infertility

DDX5 plays essential transcriptional and post-transcriptional roles in the maintenance and function of spermatogonia

Legrand JMD, Chan AL, La HM, Rossello FJ, Änkö ML, Fuller-Pace FV, Hobbs RM.

Mammalian spermatogenesis is sustained by mitotic germ cells with self-renewal potential known as undifferentiated spermatogonia. Maintenance of undifferentiated spermatogonia and spermatogenesis is dependent on tightly co-ordinated transcriptional and post-transcriptional mechanisms. The RNA helicase DDX5 is expressed by spermatogonia but roles in spermatogenesis are unexplored. Using an inducible knockout mouse model, we characterise an essential role for DDX5 in spermatogonial maintenance and show that Ddx5 is indispensable for male fertility. We demonstrate that DDX5 regulates appropriate splicing of key genes necessary for spermatogenesis. Moreover, DDX5 regulates expression of cell cycle genes in undifferentiated spermatogonia post-transcriptionally and is required for cell proliferation and survival. DDX5 can also act as a transcriptional co-activator and we demonstrate that DDX5 interacts with PLZF, a transcription factor required for germline maintenance, to co-regulate select target genes. Combined, our data reveal a critical multifunctional role for DDX5 in regulating gene expression programmes and activity of undifferentiated spermatogonia. FAU - Legrand, Julien M D AU - Legrand JMD AUID- ORCID: 0000-0001-5577-5645 AD - Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, 3800, Australia. AD - Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, 3800, Australia. FAU - Chan, Ai-Leen AU - Chan AL AD - Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, 3800, Australia. AD - Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, 3800, Australia. FAU - La, Hue M AU - La HM AUID- ORCID: 0000-0003-4549-7017 AD - Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, 3800, Australia. AD - Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, 3800, Australia. FAU - Rossello, Fernando J AU - Rossello FJ AD - Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, 3800, Australia. AD - University of Melbourne Centre for Cancer Research, The University of Melbourne, Melbourne, Victoria, 3000, Australia. FAU - Änkö, Minna-Liisa AU - Änkö ML AD - Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC, 3800, Australia. AD - Centre for Reproductive Health and Centre for Cancer Research, Hudson Institute of Medical Research and Department of Molecular and Translational Science, Monash University, Melbourne, VIC, 3168, Australia. FAU - Fuller-Pace, Frances V AU - Fuller-Pace FV AD - Jacqui Wood Cancer Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK.