{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T23:23:45Z","timestamp":1785540225697,"version":"3.56.0"},"reference-count":70,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 107-2314-B-040-018"],"award-info":[{"award-number":["MOST 107-2314-B-040-018"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 105-2314-B-040-018-"],"award-info":[{"award-number":["MOST 105-2314-B-040-018-"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 103-2314-B-022"],"award-info":[{"award-number":["MOST 103-2314-B-022"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Blastocyst vitrification has significantly improved embryo transfer methods, leading to higher implantation success rates and better pregnancy outcomes in subsequent frozen embryo transfer cycles. This study aimed to simulate the transcriptional changes caused by vitrifying human blastocysts using mouse blastocysts as a model and to further investigate these changes\u2019 effects. Utilizing a human vitrification protocol, we implanted both vitrified and fresh embryos into mice. We observed the implantation success rates and performed transcriptomic analysis on the blastocysts. To validate the results from messenger RNA sequencing, we conducted reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) to measure the expression levels of specific genes. Based on mRNA profiling, we predicted the microRNAs responsible for the regulation and used qPCR basic microRNA assays for validation. Our observations revealed a higher implantation success rate for vitrified embryos than fresh embryos. Transcriptomic analysis showed that vitrified\u2013warmed blastocysts exhibited differentially expressed genes (DEGs) primarily associated with thermogenesis, chemical carcinogenesis-reactive oxygen species, oxidative phosphorylation, immune response, and MAPK-related signaling pathways. RT-qPCR confirmed increased expression of genes such as Cdk6 and Nfat2, and decreased expression of genes such as Dkk3 and Mapk10. Additionally, gene-microRNA interaction predictions and microRNA expression analysis identified twelve microRNAs with expression patterns consistent with the predicted results, suggesting potential roles in uterine epithelial cell adhesion, trophectoderm development, invasive capacity, and immune responses. Our findings suggest that vitrification induces transcriptomic changes in mouse blastocysts, and even small changes in gene expression can enhance implantation success. These results highlight the importance of understanding the molecular mechanisms underlying vitrification to optimize embryo transfer techniques and improve pregnancy outcomes.<\/jats:p>","DOI":"10.3390\/ijms25168658","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T15:04:24Z","timestamp":1723129464000},"page":"8658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Transcriptomic Analysis of Vitrified\u2013Warmed vs. Fresh Mouse Blastocysts: Cryo-Induced Physiological Mechanisms and Implantation Impact"],"prefix":"10.3390","volume":"25","author":[{"given":"Chi-Ying","family":"Lee","sequence":"first","affiliation":[{"name":"Genetic Diagnosis Laboratory, Lee Women\u2019s Hospital, Taichung 40652, Taiwan"},{"name":"Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Ni","family":"Tsai","sequence":"additional","affiliation":[{"name":"Genetic Diagnosis Laboratory, Lee Women\u2019s Hospital, Taichung 40652, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En-Hui","family":"Cheng","sequence":"additional","affiliation":[{"name":"Genetic Diagnosis Laboratory, Lee Women\u2019s Hospital, Taichung 40652, Taiwan"},{"name":"Post Baccalaureate Medicine, National Chung Hsing University, Taichung 40227, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8858-0916","authenticated-orcid":false,"given":"Tsung-Hsien","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Infertility, Lee Women\u2019s Hospital, Taichung 40402, Taiwan"},{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4602-5732","authenticated-orcid":false,"given":"Pin-Yao","family":"Lin","sequence":"additional","affiliation":[{"name":"Post Baccalaureate Medicine, National Chung Hsing University, Taichung 40227, Taiwan"},{"name":"Division of Infertility, Lee Women\u2019s Hospital, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maw-Sheng","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Infertility, Lee Women\u2019s Hospital, Taichung 40402, Taiwan"},{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"},{"name":"Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-I","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Infertility, Lee Women\u2019s Hospital, Taichung 40402, Taiwan"},{"name":"Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan"},{"name":"Department of Obstetrics and Gynecology, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.fertnstert.2012.05.019","article-title":"Obstetric and Perinatal Outcomes in Singleton Pregnancies Resulting from the Transfer of Frozen Thawed Versus Fresh Embryos Generated through in Vitro Fertilization Treatment: A Systematic Review and Meta-Analysis","volume":"98","author":"Abha","year":"2012","journal-title":"Fertil. Steril."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/humupd\/dmx031","article-title":"Is Frozen Embryo Transfer Better for Mothers and Babies? Can Cumulative Meta-Analysis Provide a Definitive Answer?","volume":"24","author":"Abha","year":"2018","journal-title":"Hum. Reprod. Update"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.fertnstert.2013.09.025","article-title":"Impact of Frozen-Thawed Single-Blastocyst Transfer on Maternal and Neonatal Outcome: An Analysis of 277,042 Single-Embryo Transfer Cycles from 2008 to 2010 in Japan","volume":"101","author":"Osamu","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1056\/NEJMoa1705334","article-title":"Transfer of Fresh versus Frozen Embryos in Ovulatory Women","volume":"378","author":"Shi","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sharov, A.A., Piao, Y., Matoba, R., Dudekula, D.B., Qian, Y., VanBuren, V., Falco, G., Martin, P.R., Stagg, C.A., and Bassey, U.C. (2003). Transcriptome Analysis of Mouse Stem Cells and Early Embryos. PLoS Biol., 1.","DOI":"10.1371\/journal.pbio.0000074"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Liang, J., Wang, S., and Wang, Z. (2017). Role of Micrornas in Embryo Implantation. Reprod. Biol. Endocrinol., 15.","DOI":"10.1186\/s12958-017-0309-7"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Cuello, C., Martinez, C.A., Cambra, J.M., Parrilla, I., Rodriguez-Martinez, H., Gil, M.A., and Martinez, E.A. (2021). Effects of Vitrification on the Blastocyst Gene Expression Profile in a Porcine Model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031222"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Martinez, E.A., Martinez, C.A., Nohalez, A., Sanchez-Osorio, J., Vazquez, J.M., Roca, J., Parrilla, I., Gil, M.A., and Cuello, C. (2015). Nonsurgical Deep Uterine Transfer of Vitrified, in Vivo-Derived, Porcine Embryos Is as Effective as the Default Surgical Approach. Sci. Rep., 5.","DOI":"10.1038\/srep10587"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/S1472-6483(10)61091-7","article-title":"Are Programmable Freezers Still Needed in the Embryo Laboratory? Review on Vitrification","volume":"12","author":"Vajta","year":"2006","journal-title":"Reprod. Biomed. Online"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/S1472-6483(10)60837-1","article-title":"Highly Efficient Vitrification Method for Cryopreservation of Human Oocytes","volume":"11","author":"Kuwayama","year":"2005","journal-title":"Reprod. Biomed. Online"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/brv.12459","article-title":"Roles of Micrornas in Mammalian Reproduction: From the Commitment of Germ Cells to Peri-Implantation Embryos","volume":"94","author":"Reza","year":"2019","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s10561-020-09870-z","article-title":"Effect of Vitrification on Biogenesis Pathway and Expression of Development-Related Micrornas in Preimplantation Mouse Embryos","volume":"22","author":"Azizi","year":"2021","journal-title":"Cell Tissue Bank."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"Shinygo: A Graphical Gene-Set Enrichment Tool for Animals and Plants","volume":"36","author":"Ge","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng1180","article-title":"Pgc-1alpha-Responsive Genes Involved in Oxidative Phosphorylation Are Coordinately Downregulated in Human Diabetes","volume":"34","author":"Mootha","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene Set Enrichment Analysis: A Knowledge-Based Approach for Interpreting Genome-Wide Expression Profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1016\/j.fertnstert.2011.01.022","article-title":"Vitrified-Warmed Blastocyst Transfer Cycles Yield Higher Pregnancy and Implantation Rates Compared with Fresh Blastocyst Transfer Cycles\u2014Time for a New Embryo Transfer Strategy?","volume":"95","author":"Zhu","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S180","DOI":"10.1016\/j.fertnstert.2013.07.1423","article-title":"Equivalent Pregnancy Rates Obtained from Vitrified and Fresh Blastocyst Transfer","volume":"100","author":"Bing","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s10815-012-9874-z","article-title":"Comparison of the Clinical Outcomes between Fresh Blastocyst and Vitrified-Thawed Blastocyst Transfer","volume":"29","author":"Ku","year":"2012","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhao, X., Hao, H., Du, W., and Zhu, H. (2015). Effect of Vitrification on the Microrna Transcriptome in Mouse Blastocysts. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123451"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.theriogenology.2020.09.014","article-title":"Inhibiting Diacylglycerol Acyltransferase-1 Reduces Lipid Biosynthesis in Bovine Blastocysts Produced In vitro","volume":"158","author":"Cajas","year":"2020","journal-title":"Theriogenology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hara, T., Kin, A., Aoki, S., Nakamura, S., Shirasuna, K., Kuwayama, T., and Iwata, H. (2018). Resveratrol Enhances the Clearance of Mitochondrial Damage by Vitrification and Improves the Development of Vitrified-Warmed Bovine Embryos. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0204571"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Martino, N.A., Dell\u2019Aquila, M.E., Cardone, R.A., Somoskoi, B., Lacalandra, G.M., and Cseh, S. (2013). Vitrification Preserves Chromatin Integrity, Bioenergy Potential and Oxidative Parameters in Mouse Embryos. Reprod. Biol. Endocrinol., 11.","DOI":"10.1186\/1477-7827-11-27"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/humupd\/dmu063","article-title":"The Effect of Cryopreservation on the Genome of Gametes and Embryos: Principles of Cryobiology and Critical Appraisal of the Evidence","volume":"21","author":"Kopeika","year":"2014","journal-title":"Hum. Reprod. Update"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1002\/cbin.10086","article-title":"Cold Exposure Lowers Energy Expenditure at the Cellular Level","volume":"37","author":"Park","year":"2013","journal-title":"Cell Biol. Int."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lan, T., Zhang, K., Lin, F., He, Q., Wu, S., Xu, Z., Zhang, Y., and Quan, F. (2022). Effects of Micu1-Mediated Mitochondrial Calcium Uptake on Energy Metabolism and Quality of Vitrified-Thawed Mouse Metaphase II Oocytes. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158629"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/sj.cr.7290105","article-title":"MAPK signal pathways in the regulation of cell proliferation in mammalian cells","volume":"12","author":"Zhang","year":"2002","journal-title":"Cell Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.stem.2010.11.027","article-title":"Calcineurin-Nfat Signaling Critically Regulates Early Lineage Specification in Mouse Embryonic Stem Cells and Embryos","volume":"8","author":"Li","year":"2011","journal-title":"Cell Stem Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/j.1600-079X.2011.00944.x","article-title":"Melatonin Promotes Embryonic Development and Reduces Reactive Oxygen Species in Vitrified Mouse 2-Cell Embryos","volume":"52","author":"Gao","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1002\/mrd.21389","article-title":"Recovery of Mitochondrial Function and Endogenous Antioxidant Systems in Vitrified Bovine Oocytes During Extended in Vitro Culture","volume":"78","author":"Zhao","year":"2011","journal-title":"Mol. Reprod. Dev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2199","DOI":"10.1038\/cddis.2016.97","article-title":"Cell Cycle and Apoptosis Regulation by Nfat Transcription Factors: New Roles for an Old Player","volume":"7","author":"Mognol","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ccr.2013.07.012","article-title":"A Kinase-Independent Function of Cdk6 Links the Cell Cycle to Tumor Angiogenesis","volume":"24","author":"Kollmann","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3543","DOI":"10.1074\/jbc.275.5.3543","article-title":"Identification of Amino Acid Residues and Protein Kinases Involved in the Regulation of Nfatc Subcellular Localization","volume":"275","author":"Porter","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Leonard, J.L., Leonard, D.M., Wolfe, S.A., Liu, J., Rivera, J., Yang, M., Leonard, R.T., Johnson, J.P.S., Kumar, P., and Liebmann, K.L. (2017). The Dkk3 Gene Encodes a Vital Intracellular Regulator of Cell Proliferation. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181724"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/35104560","article-title":"Induction of Gadd45beta by Nf-Kappab Downregulates Pro-Apoptotic Jnk Signalling","volume":"414","author":"Zazzeroni","year":"2001","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/molehr\/7.2.175","article-title":"The Nf-Kappab Pathway in Human Endometrium and First Trimester Decidua","volume":"7","author":"King","year":"2001","journal-title":"Mol. Hum. Reprod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/jmor.20010","article-title":"Focal Adhesion Kinase Localizes to Sites of Cell-to-Cell Contact in Vivo and Increases Apically in Rat Uterine Luminal Epithelium and the Blastocyst at the Time of Implantation","volume":"273","author":"Kaneko","year":"2012","journal-title":"J. Morphol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1210\/me.2016-1050","article-title":"miR-200 Regulates Endometrial Development During Early Pregnancy","volume":"30","author":"Jimenez","year":"2016","journal-title":"Mol. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1177\/1933719113488453","article-title":"Mmu-Microrna-200a Overexpression Leads to Implantation Defect by Targeting Phosphatase and Tensin Homolog in Mouse Uterus","volume":"20","author":"Shen","year":"2013","journal-title":"Reprod. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"H931","DOI":"10.1152\/ajpheart.00338.2012","article-title":"Mirnas in Esc Differentiation","volume":"303","author":"Berardi","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1126\/science.1237999","article-title":"Mir-200b and Mir-429 Function in Mouse Ovulation and Are Essential for Female Fertility","volume":"341","author":"Hasuwa","year":"2013","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ydbio.2008.11.016","article-title":"Mir-17 Family Mirnas Are Expressed During Early Mammalian Development and Regulate Stem Cell Differentiation","volume":"326","author":"Foshay","year":"2009","journal-title":"Dev. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1007\/s43032-019-00003-w","article-title":"MiR-93 Inhibits Trophoblast Cell Proliferation and Promotes Cell Apoptosis by Targeting BCL2L2 in Recurrent Spontaneous Abortion","volume":"27","author":"Liu","year":"2020","journal-title":"Reprod. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.placenta.2020.02.019","article-title":"Mir-150-5p Mediates Extravillous Trophoblast Cell Migration and Angiogenesis Functions by Regulating Vegf and Mmp9","volume":"93","author":"Zeng","year":"2020","journal-title":"Placenta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.it.2008.04.004","article-title":"Micrornas and the Immune Response","volume":"29","author":"Mark","year":"2008","journal-title":"Trends Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4681","DOI":"10.1038\/s41388-020-1322-4","article-title":"Cancer Exosome-Derived Mir-9 and Mir-181a Promote the Development of Early-Stage Mdscs Via Interfering with Socs3 and Pias3 Respectively in Breast Cancer","volume":"39","author":"Jiang","year":"2020","journal-title":"Oncogene"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.bbrc.2012.12.097","article-title":"Mir-9 Modulates the Expression of Interferon-Regulated Genes and Mhc Class I Molecules in Human Nasopharyngeal Carcinoma Cells","volume":"431","author":"Gao","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5081","DOI":"10.1038\/onc.2012.15","article-title":"Inhibition of Mir-9 De-Represses Hur and Dicer1 and Impairs Hodgkin Lymphoma Tumour Outgrowth in Vivo","volume":"31","author":"Leucci","year":"2012","journal-title":"Oncogene"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Smith, N.L., Wissink, E.M., Grimson, A., and Rudd, B.D. (2015). miR-150 Regulates Differentiation and Cytolytic Effector Function in CD8+ T cells. Sci. Rep., 5.","DOI":"10.1038\/srep16399"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"M\u00e9noret, A., Agliano, F., Karginov, T.A., Karlinsey, K.S., Zhou, B., and Vella, A.T. (2023). Antigen-Specific Downregulation of Mir-150 in Cd4 T Cells Promotes Cell Survival. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1102403"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.neo.2015.04.005","article-title":"Stat1: A Novel Target of Mir-150 and Mir-223 Is Involved in the Proliferation of Htlv-I-Transformed and Atl Cells","volume":"17","author":"Moles","year":"2015","journal-title":"Neoplasia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1038\/ncb3615","article-title":"Mir-25\/93 Mediates Hypoxia-Induced Immunosuppression by Repressing Cgas","volume":"19","author":"Wu","year":"2017","journal-title":"Nat. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"21609","DOI":"10.18632\/oncotarget.15450","article-title":"The Mir-25-93-106b Cluster Regulates Tumor Metastasis and Immune Evasion Via Modulation of Cxcl12 and Pd-L1","volume":"8","author":"Cioffi","year":"2017","journal-title":"Oncotarget"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/carcin\/bgt320","article-title":"Mir-200b Suppresses Invasiveness and Modulates the Cytoskeletal and Adhesive Machinery in Esophageal Squamous Cell Carcinoma Cells Via Targeting Kindlin-2","volume":"35","author":"Zhang","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7053","DOI":"10.1182\/blood-2010-12-326629","article-title":"Modulation of Microrna Expression in Human T-Cell Development: Targeting of Notch3 by Mir-150","volume":"117","author":"Ghisi","year":"2011","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1016\/j.ebiom.2015.09.003","article-title":"Human Blastocyst Secreted microRNA Regulate Endometrial Epithelial Cell Adhesion","volume":"2","author":"Cuman","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.stem.2010.02.015","article-title":"Microrna-9 Coordinates Proliferation and Migration of Human Embryonic Stem Cell-Derived Neural Progenitors","volume":"6","author":"Delaloy","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Su, J., Kong, W., Fang, Z., Li, Y., Huang, Z., Wen, J., and Wang, Y. (2021). Roles of miR-10a-5p and miR-103a-3p, Regulators of BDNF Expression in Follicular Fluid, in the Outcomes of IVF-ET. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.637384"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Goharitaban, S., Abedelahi, A., Hamdi, K., Khazaei, M., Esmaeilivand, M., and Niknafs, B. (2022). Role of Endometrial Micrornas in Repeated Implantation Failure (Mini-Review). Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.936173"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Zeng, H., Fu, Y., Shen, L., and Quan, S. (2021). Microrna Signatures in Plasma and Plasma Exosome During Window of Implantation for Implantation Failure Following in-Vitro Fertilization and Embryo Transfer. Reprod. Biol. Endocrinol., 19.","DOI":"10.1186\/s12958-021-00855-5"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Xu, X., Li, W., Zhang, L., Ji, Y., Qin, J., Wang, L., Wang, M., Qi, L., Xue, J., and Lv, B. (2021). Effect of Sperm Cryopreservation on miRNA Expression and Early Embryonic Development. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.749486"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Liu, L., Liu, H., Chen, M., Ren, S., Cheng, P., and Zhang, H. (2017). Mir-301b~Mir-130b\u2014Ppar\u03b3 Axis Underlies the Adipogenic Capacity of Mesenchymal Stem Cells with Different Tissue Origins. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-01294-2"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13045-017-0415-1","article-title":"Downregulation of Mir-130b~301b Cluster Is Mediated by Aberrant Promoter Methylation and Impairs Cellular Senescence in Prostate Cancer","volume":"10","author":"Gomez","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Cheng, E.H., Liu, J.Y., Lee, T.H., Huang, C.C., Chen, C.I., Huang, L.S., and Lee, M.S. (2016). Requirement of Leukemia Inhibitory Factor or Epidermal Growth Factor for Pre-Implantation Embryogenesis via JAK\/STAT3 Signaling Pathways. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153086"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/BF02211377","article-title":"Enhanced Results in Mouse and Human Embryo Culture Using a Modified Human Tubal Fluid Medium Lacking Glucose and Phosphate","volume":"12","author":"Quinn","year":"1995","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_65","first-page":"43","article-title":"Evaluation of Mouse Blastocyst Implantation Rate by Morphology Grading","volume":"47","author":"Cheng","year":"2004","journal-title":"Chin. J. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.cryobiol.2013.08.006","article-title":"Evaluation of the Cryotech Vitrification Kit for bovine embryos","volume":"67","author":"Gutnisky","year":"2013","journal-title":"Cryobiology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/nmeth.1226","article-title":"Mapping and Quantifying Mammalian Transcriptomes by Rna-Seq","volume":"5","author":"Mortazavi","year":"2008","journal-title":"Nat. Methods"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (Msigdb) Hallmark Gene Set Collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1093\/bioinformatics\/btr260","article-title":"Molecular Signatures Database (Msigdb) 3.0","volume":"27","author":"Liberzon","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"W180","DOI":"10.1093\/nar\/gky509","article-title":"Tam 2.0: Tool for Microrna Set Analysis","volume":"46","author":"Li","year":"2018","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8658\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:32:11Z","timestamp":1760110331000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,8]]},"references-count":70,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25168658"],"URL":"https:\/\/doi.org\/10.3390\/ijms25168658","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,8]]}}}