• PMID: 28706261
• Gene Name: PLAG1
• Condition: Impairs spermatogenesis, sperm motility, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Impairs spermatogenesis, sperm motility, Male infertility

PLAG1 deficiency impairs spermatogenesis and sperm motility in mice

Juma AR, Grommen SVH, O'Bryan MK, O'Connor AE, Merriner DJ, Hall NE, Doyle SR, Damdimopoulou PE, Barriga D, Hart AH, Van de Ven WJM, De Groef B.

Deficiency in pleomorphic adenoma gene 1 (PLAG1) leads to reduced fertility in male mice, but the mechanism by which PLAG1 contributes to reproduction is unknown. To investigate the involvement of PLAG1 in testicular function, we determined (i) the spatial distribution of PLAG1 in the testis using X-gal staining; (ii) transcriptomic consequences of PLAG1 deficiency in knock-out and heterozygous mice compared to wild-type mice using RNA-seq; and (iii) morphological and functional consequences of PLAG1 deficiency by determining testicular histology, daily sperm production and sperm motility in knock-out and wild-type mice. PLAG1 was sparsely expressed in germ cells and in Sertoli cells. Genes known to be involved in spermatogenesis were downregulated in the testes of knock-out mice, as well as Hsd17b3, which encodes a key enzyme in androgen biosynthesis. In the absence of Plag1, a number of genes involved in immune processes and epididymis-specific genes were upregulated in the testes. Finally, loss of PLAG1 resulted in significantly lowered daily sperm production, in reduced sperm motility, and in several animals, in sloughing of the germinal epithelium. Our results demonstrate that the subfertility seen in male PLAG1-deficient mice is, at least in part, the result of significantly reduced sperm output and sperm motility. FAU - Juma, Almas R AU - Juma AR AD - Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, Victoria, 3086, Australia. FAU - Grommen, Sylvia V H AU - Grommen SVH AD - Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, Victoria, 3086, Australia. FAU - O'Bryan, Moira K AU - O'Bryan MK AUID- ORCID: 0000-0001-7298-4940 AD - Development and Stem Cells Program of Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, 3800, Australia. FAU - O'Connor, Anne E AU - O'Connor AE AD - Development and Stem Cells Program of Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, 3800, Australia. FAU - Merriner, D Jo AU - Merriner DJ AD - Development and Stem Cells Program of Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, 3800, Australia. FAU - Hall, Nathan E AU - Hall NE AD - Department of Biochemistry and Genetics and La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, Victoria, 3086, Australia. FAU - Doyle, Stephen R AU - Doyle SR AUID- ORCID: 0000-0001-9167-7532 AD - Department of Biochemistry and Genetics and La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, Victoria, 3086, Australia. AD - Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, United Kingdom. FAU - Damdimopoulou, Pauliina E AU - Damdimopoulou PE AD - Department of Clinical Sciences, Intervention and Technology, Karolinska Institute, and Karolinska University Hospital, 14183, Huddinge, Sweden. FAU - Barriga, Daniel AU - Barriga D AD - Department of Biochemistry and Genetics and La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, Victoria, 3086, Australia. FAU - Hart, Adam H AU - Hart AH AUID- ORCID: 0000-0001-8129-3877 AD - Department of Biochemistry and Genetics and La Trobe Institute for Molecular Sciences, La Trobe University, Bundoora, Victoria, 3086, Australia. FAU - Van de Ven, Wim J M AU - Van de Ven WJM AD - Department of Human Genetics, KU Leuven, B-3000, Leuven, Belgium.