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In particular, Leucine and Arginine have been shown to stimulate implantation, as lack of both in a blastocyst culture system is able to induce a dormant state in embryos. The aim of this work was to evaluate the effects of Leucine and Arginine withdrawal on pluripotent mouse embryonic stem cell status, notably, their growth, self-renewal, as well as glycolytic and oxidative metabolism. Our results show that the absence of both Leucine and Arginine does not affect mouse embryonic stem cell pluripotency, while reducing cell proliferation through cell-cycle arrest. Importantly, these effects are not related to Leukemia Inhibitory Factor (LIF) and are reversible when both amino acids are reconstituted in the culture media. Moreover, a lack of these amino acids is related to a reduction in glycolytic and oxidative metabolism and decreased protein translation in mouse embryonic stem cells (mESCs), while maintaining their pluripotent status.<\/jats:p>","DOI":"10.3390\/ijms232214286","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T03:29:50Z","timestamp":1668742190000},"page":"14286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Leucine and Arginine Availability Modulate Mouse Embryonic Stem Cell Proliferation and Metabolism"],"prefix":"10.3390","volume":"23","author":[{"given":"Bibiana","family":"Correia","sequence":"first","affiliation":[{"name":"Department of Life Sciences, University of Coimbra, Cal\u00e7ada Martim de Freitas, 3000-456 Coimbra, Portugal"},{"name":"CNC\u2014Center for Neuroscience and Cell Biology, CIBB, University of Coimbra, Azinhaga de Santa Comba, Polo 3, 3000-354 Coimbra, Portugal"}]},{"given":"Maria In\u00eas","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Coimbra, Cal\u00e7ada Martim de Freitas, 3000-456 Coimbra, Portugal"},{"name":"CNC\u2014Center for Neuroscience and Cell Biology, CIBB, University of Coimbra, Azinhaga de Santa Comba, Polo 3, 3000-354 Coimbra, Portugal"}]},{"given":"Ana Filipa","family":"Branco","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, CIBB, University of Coimbra, Azinhaga de Santa Comba, Polo 3, 3000-354 Coimbra, Portugal"}]},{"given":"Ana Sofia","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"CNC\u2014Center for Neuroscience and Cell Biology, CIBB, University of Coimbra, Azinhaga de Santa Comba, Polo 3, 3000-354 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-4018","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Ramalho-Santos","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, University of Coimbra, Cal\u00e7ada Martim de Freitas, 3000-456 Coimbra, Portugal"},{"name":"CNC\u2014Center for Neuroscience and Cell Biology, CIBB, University of Coimbra, Azinhaga de Santa Comba, Polo 3, 3000-354 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1095\/biolreprod42.3.432","article-title":"Development of 1-cell embryos from different strains of mice in CZB medium","volume":"42","author":"Chatot","year":"1990","journal-title":"Biol. Reprod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/978-1-4939-2480-6_2","article-title":"Amino acids and conceptus development during the peri-implantation period of pregnancy","volume":"Volume 843","author":"Bazer","year":"2015","journal-title":"Cell Signaling During Mammalian Early Embryo Development"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-2480-6_1","article-title":"Cell signalling during blastocyst morphogenesis","volume":"Volume 843","author":"Eckert","year":"2015","journal-title":"Cell Signaling During Mammalian Early Embryo Development"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/978-1-4939-2480-6_4","article-title":"Molecular biology of the stress response in the early embryo and its stem cells","volume":"Volume 843","author":"Puscheck","year":"2015","journal-title":"Cell Signaling During Mammalian Early Embryo Development"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1071\/RD14421","article-title":"Blastocyst metabolism","volume":"27","author":"Gardner","year":"2015","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Van Winkle, L.J. (2021). Amino Acid Transport and Metabolism Regulate Early Embryo Development: Species Differences, Clinical Significance, and Evolutionary Implications. Cells, 10.","DOI":"10.3390\/cells10113154"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.112.100552","article-title":"Oxygen regulates amino acid turnover and carbohydrate uptake during the preimplantation period of mouse embryo development","volume":"87","author":"Wale","year":"2012","journal-title":"Biol. Reprod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1002\/mrd.22868","article-title":"Metabolite availability as a window to view the early embryo microenvironment in vivo","volume":"84","author":"Hu","year":"2017","journal-title":"Mol. Reprod. Dev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/jcp.1040680313","article-title":"Amino acid requirements for attachment and outgrowth of the mouse blastocyst in vitro","volume":"68","author":"Gwatkin","year":"1966","journal-title":"J. Cell. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6710","DOI":"10.1128\/MCB.24.15.6710-6718.2004","article-title":"mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells","volume":"24","author":"Murakami","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.mce.2011.08.026","article-title":"Mechanistic mammalian target of rapamycin (MTOR) cell signaling: Effects of select nutrients and secreted phosphoprotein 1 on development of mammalian conceptuses","volume":"354","author":"Bazer","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.ydbio.2011.10.021","article-title":"Leucine and arginine regulate trophoblast motility through mTOR-dependent and independent pathways in the preimplantation mouse embryo","volume":"361","author":"Martin","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1530\/REP-12-0254","article-title":"Arginine enhances embryo implantation in rats through PI3K\/PKB\/mTOR\/NO signaling pathway during early pregnancy","volume":"145","author":"Zeng","year":"2013","journal-title":"Reproduction"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1126\/science.1257132","article-title":"Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1","volume":"347","author":"Wang","year":"2015","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1095\/biolreprod.112.105080","article-title":"Arginine, Leucine, and Glutamine Stimulate Proliferation of Porcine Trophectoderm Cells Through the MTOR-RPS6K-RPS6-EIF4EBP1 Signal Transduction Pathway1","volume":"88","author":"Kim","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3109\/03009737909179136","article-title":"The effect of glucose, arginine and leucine deprivation on mouse blastocyst outgrowth in vitro","volume":"84","author":"Naeslund","year":"1979","journal-title":"Upsala J. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1095\/biolreprod.110.085738","article-title":"Select nutrients in the ovine uterine lumen. VII. Effects of arginine, leucine, glutamine, and glucose on trophectoderm cell signaling, proliferation, and migration","volume":"84","author":"Kim","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nature08113","article-title":"A parallel circuit of LIF signaling pathways maintains pluripotency of mouse ES cells","volume":"460","author":"Niwa","year":"2009","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1038\/emboj.2013.177","article-title":"Identification of the missing pluripotency mediator downstream of leukaemia inhibitory factor","volume":"32","author":"Martello","year":"2013","journal-title":"EMBO J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/359076a0","article-title":"Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor","volume":"359","author":"Stewart","year":"1992","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4365","DOI":"10.1210\/endo.141.12.7855","article-title":"Leukemia inhibitory factor can substitute for nidatory estrogen and is essential to inducing a receptive uterus for implantation but is not essential for subsequente embryogenesis","volume":"141","author":"Chen","year":"2000","journal-title":"Endocrinology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1242\/dev.128.12.2333","article-title":"Physiological rationale for responsiveness of mouse embryonic stem cells to gp130 cytokines","volume":"128","author":"Nichols","year":"2001","journal-title":"Development"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1093\/biolre\/ioy112","article-title":"The history of the discovery of embryonic diapause in mammals","volume":"99","author":"Fenelon","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1038\/emboj.2012.71","article-title":"HIF1a induced switch from bivalent to exclusively glycolytic metabolism during ESC-to-EpiSC\/hESC transition","volume":"31","author":"Zhou","year":"2012","journal-title":"EMBO J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.stem.2016.05.009","article-title":"LIN28 Regulates Stem Cell Metabolism and Conversion to Primed Pluripotency","volume":"19","author":"Zhang","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.devcel.2019.12.018","article-title":"Metabolic control over mTOR-dependent diapause-like state","volume":"52","author":"Hussein","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Eckert, J.J., Porter, R., Watkins, A.J., Burt, E., Brooks, S., Leese, H.J., Humpherson, P.G., Cameron, I.T., and Fleming, T.P. (2012). Metabolic induction and early responses of mouse blastocyst developmental programming following maternal low protein diet affecting life-long health. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052791"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.cmet.2014.03.017","article-title":"Methionine metabolism regulates maintenance and differentiation of human pluripotent stem cells","volume":"19","author":"Shiraki","year":"2014","journal-title":"Cell Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1126\/science.1173288","article-title":"Dependence of mouse embryonic stem cells on threonine catabolism","volume":"325","author":"Wang","year":"2009","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"To, C.Y., Freeman, M., and Van Winkle, L.J. (2020). Consumption of a Branched-Chain Amino Acid (BCAA) during Days 2\u201310 of Pregnancy Causes Abnormal Fetal and Placental Growth: Implications for BCAA Supplementation in Humans. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17072445"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"300","DOI":"10.3389\/fcell.2019.00300","article-title":"One-carbon metabolism regulates embryonic stem cell fate through epigenetic DNA and histone modifications: Implications for transgenerational metabolic disorders in adults","volume":"7","author":"Ryznar","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3389\/fphys.2020.00140","article-title":"Selected amino acids promote mouse pre-implantation embryo development in a growth factor-like manner","volume":"11","author":"Morris","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e201900413","DOI":"10.26508\/lsa.201900413","article-title":"Glycine cleavage system determines the fate of pluripotent stem cells via the regulation of senescence and epigenetic modifications","volume":"2","author":"Tian","year":"2019","journal-title":"Life Sci. Alliance"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/jez.1402530211","article-title":"Glycine protects preimplantation mouse conceptuses from a detrimental effect on development of the inorganic ions in oviductal fluid","volume":"253","author":"Haghighat","year":"1990","journal-title":"J. Exp. Zool."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nature20578","article-title":"Inhibition of mTOR induces a paused pluripotent state","volume":"540","author":"Biechele","year":"2016","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/ncb2965","article-title":"The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification","volume":"16","author":"Boroviak","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.cell.2015.12.033","article-title":"Myc Depletion Induces a Pluripotent Dormant State Mimicking Diapause","volume":"164","author":"Scognamiglio","year":"2016","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1095\/biolreprod.103.018010","article-title":"Amino acid transport regulates blastocyst implantation","volume":"69","author":"Martin","year":"2003","journal-title":"Biol. Reprod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nature06968","article-title":"The ground state of embryonic stem cell self-renewal","volume":"453","author":"Ying","year":"2008","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1042\/BST0381027","article-title":"The ground state of pluripotency","volume":"38","author":"Wray","year":"2010","journal-title":"Biochem. Soc. Trans."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/ncb2267","article-title":"Inhibition of glycogen synthase kinase-3 alleviates Tcf3 repression of the pluripotency network and increases embryonic stem cell resistance to differentiation","volume":"13","author":"Wray","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1242\/jcs.118273","article-title":"Gbx2, a LIF\/Stat3 target, promotes reprogramming to and retention of the pluripotent ground state","volume":"126","author":"Tai","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1038\/emboj.2013.175","article-title":"Embryonic stem cell self-renewal pathways converge on the transcription factor Tfcp2l1","volume":"32","author":"Ye","year":"2013","journal-title":"EMBO J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1095\/biolreprod.113.115337","article-title":"Integral proteomic analysis of blastocysts reveals key molecular machinery governing embryonic diapause and reactivation for implantation in mice","volume":"90","author":"Fu","year":"2014","journal-title":"Biol. Reprod."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1242\/dev.148213","article-title":"The enigma of embryonic diapause","volume":"144","author":"Renfree","year":"2017","journal-title":"Development"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/B978-0-12-396968-2.00008-7","article-title":"Diapause: Delaying the developmental clock in response to a changing environment","volume":"105","author":"Schiesari","year":"2013","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/gb-2004-6-1-202","article-title":"Profiling gene expression in growth-arrested mouse embryos in diapause","volume":"6","author":"Hondo","year":"2004","journal-title":"Genome Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1387\/ijdb.140074bm","article-title":"Embryonic diapause: Development on hold","volume":"58","author":"Fenelon","year":"2014","journal-title":"Int. J. Dev. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"14484","DOI":"10.1074\/jbc.273.23.14484","article-title":"Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism","volume":"273","author":"Hara","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1007\/s13402-022-00706-4","article-title":"Dual contribution of the mTOR pathway and of the metabolism of amino acids in prostate cancer","volume":"45","year":"2022","journal-title":"Cell. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1476-4598-6-37","article-title":"hZip2 and hZip3 zinc transporters are down regulated in human prostate adenocarcinomatous glands","volume":"6","author":"Desouki","year":"2007","journal-title":"Mol. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1038\/s41467-021-22652-9","article-title":"Arginine is an epigenetic regulator targeting TEAD4 to modulate OXPHOS in prostate cancer cells","volume":"12","author":"Chen","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s12265-012-9431-2","article-title":"Nuclear reprogramming with c-Myc potentiates glycolytic capacity of derived induced pluripotent stem cells","volume":"6","author":"Folmes","year":"2013","journal-title":"J. Cardiovasc. Transl. Res"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"609","DOI":"10.15252\/embj.201490441","article-title":"miR-290\/371-Mbd2-Myc circuit regulates glycolytic metabolism to promote pluripotency","volume":"34","author":"Cao","year":"2015","journal-title":"EMBO J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.gde.2017.06.008","article-title":"Metabolic switching and cell fate decisions: Implications for pluripotency, reprogramming and development","volume":"46","author":"Cliff","year":"2017","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1091\/mbc.e13-02-0106","article-title":"A complex of Cox4 and mitochondrial Hsp70 plays an important role in the assembly of the cytochrome c oxidase","volume":"24","author":"Guiard","year":"2013","journal-title":"Mol. Biol. Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.scr.2009.07.002","article-title":"Enhancement of human embryonic stem cell pluripotency through inhibition of the mitochondrial respiratory chain","volume":"3","author":"Varum","year":"2009","journal-title":"Stem Cell Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Varum, S., Rodrigues, A.S., Moura, M.B., Momcilovic, O., Iv, C.A.E., Ramalho-Santos, J., Van Houten, B., and Schatten, G. (2011). Energy metabolism in human pluripotent stem cells and their differentiated counterparts. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020914"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Pereira, S.L., Gr\u00e3os, M., Rodrigues, A.S., Anjo, S.I., Carvalho, R.A., Oliveira, P.J., Arenas, E., and Ramalho-Santos, J. (2013). Inhibition of mitochondrial complex III blocks neuronal differentiation and maintains embryonic stem cell pluripotency. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082095"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Rodrigues, A.S., Correia, M., Gomes, A., Pereira, S.L., Perestrelo, T., Sousa, M.I., and Ramalho-Santos, J. (2015). Dichloroacetate, the pyruvate dehydrogenase complex and the modulation of mESC pluripotency. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131663"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Rodrigues, A.S., Pereira, S.L., Correia, M., Gomes, A., Perestrelo, T., and Ramalho-Santos, J. (2015). Differentiate or die: 3-bromopyruvate and pluripotency in mouse embryonic stem cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135617"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"129612","DOI":"10.1016\/j.bbagen.2020.129612","article-title":"Metabolic characterization of a paused-like pluripotent state","volume":"1864","author":"Sousa","year":"2020","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.fct.2015.12.011","article-title":"Different concentrations of kaempferol distinctly modulate murine embryonic stem cell function","volume":"87","author":"Correia","year":"2016","journal-title":"Food Chem. 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