Mouse prolyl oligopeptidase plays a role in trophoblast stem cell differentiation into trophoblast giant cell and spongiotrophoblast |
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| Institution: | 1. Graduate School of Life Science, Hokkaido University, Sapporo 060-0810, Japan;2. Department of Biological Sciences, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan;1. Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia;2. Department of Molecular and Translational Medicine, Monash University, Clayton, VIC, Australia;3. Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, VIC, Australia;4. Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia;1. Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia;2. Mercy Perinatal Research Centre, Mercy Hospital for Women, Victoria, Australia;1. Department of Obstetrics and Gynaecology, Spaarne Gasthuis, Spaarnepoort 1, 2134 TM, Hoofddorp, The Netherlands;2. Department of Clinical Pathology, Spaarne Gasthuis, Spaarnepoort 1, 2134 TM, Hoofddorp, The Netherlands;3. Department of Obstetrics and Gynaecology, Division of Obstetrics and Prenatal Medicine, Erasmus MC: University Medical Centre Rotterdam, ''s-Gravendijkwal 230, 3015 CE, The Netherlands;1. Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan;2. Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan;3. Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan;4. Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan;1. Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan;2. School of Biomedical Sciences, The University of Queensland, Brisbane, Australia;3. Commonwealth Scientific and Industrial Research Organization (CSIRO), Agriculture Flagship, St Lucia, QLD 4067, Australia;1. Center for RNA Science and Therapeutics, Case Western Reserve University, Cleveland, OH 44106, USA |
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| Abstract: | IntroductionProlyl oligopeptidase (prolyl endopeptidase, Prep), a multifunctional protease hydrolyzing -Pro-X- peptide bonds, is highly expressed in the mouse placenta, but the function during development is not known. We explored the possibility of Prep's involvement in placental differentiation.MethodsWe cultured trophoblast stem cells (TSCs) derived from the E6.5 mouse embryo and investigated the detailed expression pattern of Prep during their differentiation. Prep-specific inhibitors were added to the TSC culture, and the effect on the differentiation was assessed by microscopic observation and the expression of marker gene for each placental cell.ResultsDuring TSC differentiation for 6 days, Prep was constantly detected at mRNA, protein, and activity levels, and the protein was found mainly in the cytoplasm. The addition of 30 μM and 10 μM SUAM-14746, a Prep-specific inhibitor, effectively inhibited the differentiation into spongiotrophoblasts (SpTs) and trophoblast giant cells (TGCs), while the TSC viability was not affected. 5 μM SUAM-14746 impaired the differentiation into SpTs, and 1 μM SUAM-14746 exhibited no effects. Another Prep-specific inhibitor, KYP-2047, did not affect the differentiation. We confirmed efficient inhibition of Prep enzymatic activity in TSCs by both inhibitors.ConclusionThe dose-dependent effect of SUAM-14746 on TSCs suggests that Prep plays an important role in the differentiation into SpTs and TGCs in the mouse placenta. |
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