The role of HnrnpF/H as a driver of oligoteratozoospermia
Jacob K. Netherton,
Rachel A. Ogle,
Benjamin R. Robinson,
Mark Molloy,
Christoph Krisp,
Tony Velkov,
Franca Casagranda,
Nicole Dominado,
Ana Izabel Silva Balbin Villaverde,
Xu Dong Zhang,
Gary R. Hime,
Mark A. Baker
Affiliations
Jacob K. Netherton
School of Biomedical Sciences and Pharmacy, Faculty of Medicine and Health, University of Newcastle, Callaghan, NSW 2308, Australia
Rachel A. Ogle
School of Biomedical Sciences and Pharmacy, Faculty of Medicine and Health, University of Newcastle, Callaghan, NSW 2308, Australia
Benjamin R. Robinson
School of Biomedical Sciences and Pharmacy, Faculty of Medicine and Health, University of Newcastle, Callaghan, NSW 2308, Australia
Mark Molloy
Australian Proteome Analysis Facility, Department of Biomolecular Sciences, Macquarie University, NSW 2109 Australia
Christoph Krisp
Australian Proteome Analysis Facility, Department of Biomolecular Sciences, Macquarie University, NSW 2109 Australia
Tony Velkov
Biomedicine Discovery Institute, Infection & Immunity Program and Department of Microbiology, Monash University, Clayton, VIC 3168, Australia
Franca Casagranda
Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC 3010, Australia
Nicole Dominado
Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC 3010, Australia
Ana Izabel Silva Balbin Villaverde
Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
Xu Dong Zhang
School of Biomedical Sciences and Pharmacy, Faculty of Medicine and Health, University of Newcastle, Callaghan, NSW 2308, Australia
Gary R. Hime
Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC 3010, Australia
Mark A. Baker
School of Biomedical Sciences and Pharmacy, Faculty of Medicine and Health, University of Newcastle, Callaghan, NSW 2308, Australia; Corresponding author.
Summary: Male subfertility or infertility is a common condition often characterized by men producing a low number of sperm with poor quality. To gain insight into this condition, we performed a quantitative proteomic analysis of semen samples obtained from infertile and fertile men. At least 6 proteins showed significant differences in regulation of alternatively spliced isoforms. To investigate this link between aberrant alternative splicing and production of poor-quality spermatozoa, we overexpressed the hnrnpH/F-orthologue Glorund (Glo) in Drosophila, which was also found to be abundant in poor quality human sperm. Transgenic animals produced low numbers of morphologically defective spermatozoa and aberrant formation of the “dense body,” an organelle akin to the mammalian manchette. Furthermore, fertility trials demonstrated that transgenic flies were either completely infertile or highly subfertile. These findings suggest that dysregulation of hnrnpH/F is likely to result in the production of low-quality semen, leading to subfertility or infertility in men.
