Sarah S K Yue1, John M Hutson2, Ruili Li3. 1. FD Stephens Surgical Research Group, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia. 2. FD Stephens Surgical Research Group, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia; Urology Department, The Royal Children's Hospital, Parkville, VIC 3052, Australia. 3. FD Stephens Surgical Research Group, Murdoch Children's Research Institute, Parkville, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia. Electronic address: ruili.li@mcri.edu.au.
Abstract
BACKGROUND/AIMS: Early germ cell development is deranged in undescended testis, potentially leading to infertility and cancer. Androgens are proposed to regulate gonocyte transformation into stem cells during human 'minipuberty' at 3-12months. We studied genes expressed in germ cells, Sertoli cells, and other somatic cells to determine whether androgen mediates gonocyte transformation. METHODS: Testes from androgen-receptor knockout (ARKO) and wild-type (WT) littermates were collected at postnatal day P0 (birth), P4, P8 for real-time PCR to measure gene expression of mouse VASA homolog (Mvh), anti-Mullerian hormone (Amh), kit oncogene (c-Kit), matrix metalloproteinase-1 (Mt1-mmp), zinc finger, and BTB domain-containing 16 (Plzf) and octamer-binding protein 4 (Oct4). Data were normalized to ribosomal protein L32 (Rpl32), and reproductive homeobox gene 5 (Rhox5) was a positive control for androgenic response. Changes in gene expression were calculated with GraphPad Prism 5.02. RESULTS: There were no statistical differences (p>0.05) in Mvh, Oct4, c-Kit, Plzf, Amh and Mt1-mmp expression between WT and ARKO testes from P0 to P8. CONCLUSION: These results show that androgen did not influence gene expression in postnatal mouse testis, which coincides with human 'minipuberty'. The results are consistent with gonocyte transformation being independent of androgens, and that nonandrogenic regulators need to be identified.
BACKGROUND/AIMS: Early germ cell development is deranged in undescended testis, potentially leading to infertility and cancer. Androgens are proposed to regulate gonocyte transformation into stem cells during human 'minipuberty' at 3-12months. We studied genes expressed in germ cells, Sertoli cells, and other somatic cells to determine whether androgen mediates gonocyte transformation. METHODS: Testes from androgen-receptor knockout (ARKO) and wild-type (WT) littermates were collected at postnatal day P0 (birth), P4, P8 for real-time PCR to measure gene expression of mouseVASA homolog (Mvh), anti-Mullerian hormone (Amh), kit oncogene (c-Kit), matrix metalloproteinase-1 (Mt1-mmp), zinc finger, and BTB domain-containing 16 (Plzf) and octamer-binding protein 4 (Oct4). Data were normalized to ribosomal protein L32 (Rpl32), and reproductive homeobox gene 5 (Rhox5) was a positive control for androgenic response. Changes in gene expression were calculated with GraphPad Prism 5.02. RESULTS: There were no statistical differences (p>0.05) in Mvh, Oct4, c-Kit, Plzf, Amh and Mt1-mmp expression between WT and ARKO testes from P0 to P8. CONCLUSION: These results show that androgen did not influence gene expression in postnatal mouse testis, which coincides with human 'minipuberty'. The results are consistent with gonocyte transformation being independent of androgens, and that nonandrogenic regulators need to be identified.
Authors: Wiwat Rodprasert; Helena E Virtanen; Juho-Antti Mäkelä; Jorma Toppari Journal: Front Endocrinol (Lausanne) Date: 2020-01-15 Impact factor: 5.555