Identification of the Inner Cell Mass and the Trophectoderm Responses after an In Vitro Exposure to Glucose and Insulin during the Preimplantation Period in the Rabbit Embryo

Romina Via Y Rada, Nathalie Daniel, Catherine Archilla, Anne Frambourg, Luc Jouneau, Yan Jaszczyszyn, Gilles Charpigny, Véronique Duranthon, Sophie Calderari, Romina Via Y Rada, Nathalie Daniel, Catherine Archilla, Anne Frambourg, Luc Jouneau, Yan Jaszczyszyn, Gilles Charpigny, Véronique Duranthon, Sophie Calderari

Abstract

The prevalence of metabolic diseases is increasing, leading to more women entering pregnancy with alterations in the glucose-insulin axis. The aim of this work was to investigate the effect of a hyperglycemic and/or hyperinsulinemic environment on the development of the preimplantation embryo. In rabbit embryos developed in vitro in the presence of high insulin (HI), high glucose (HG), or both (HGI), we determined the transcriptomes of the inner cell mass (ICM) and the trophectoderm (TE). HI induced 10 differentially expressed genes (DEG) in ICM and 1 in TE. HG ICM exhibited 41 DEGs involved in oxidative phosphorylation (OXPHOS) and cell number regulation. In HG ICM, proliferation was decreased (p < 0.01) and apoptosis increased (p < 0.001). HG TE displayed 132 DEG linked to mTOR signaling and regulation of cell number. In HG TE, proliferation was increased (p < 0.001) and apoptosis decreased (p < 0.001). HGI ICM presented 39 DEG involved in OXPHOS and no differences in proliferation and apoptosis. HGI TE showed 16 DEG linked to OXPHOS and cell number regulation and exhibited increased proliferation (p < 0.001). Exposure to HG and HGI during preimplantation development results in common and specific ICM and TE responses that could compromise the development of the future individual and placenta.

Keywords: DOHaD; diabetes; preimplantation embryo; rabbit.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the experimental workflow to analyze the in vitro exposure of preimplantation embryos from 1-cell to blastocyst stage for control, high insulin, high glucose, and high glucose and high insulin. The inner cell mass (ICM) and trophectoderm (TE) transcriptomes were determined by RNA-seq. D1, day 1. D4, day 4.
Figure 2
Figure 2
Transcriptome analysis of isolated ICM and TE from in vitro-developed blastocysts with high glucose and/or high insulin. (A). Clustering by Euclidean distance of the transcriptomic datasets of ICM and their corresponding TE developed in CNTRL, HI, HG, or HGI. Each group included three biological replicates which consisted of n = 11-16 ICM or TE. (B). Principal component analysis (PCA) of ICM groups. (C). PCA of TE groups. ICM, inner cell mass. TE, trophectoderm. CNTRL, control; HI, high insulin; HG, high glucose; HGI, high glucose and high insulin. Samples are color-coded according to the legend at the top (right).
Figure 3
Figure 3
Differentially expressed genes (DEG) in ICM and TE of in vitro-developed blastocysts with HI, HG, or HGI compared to CNTRL. The number of overexpressed (red) and underexpressed (blue) DEGs with p-adjusted < 0.05 are shown. ICM, inner cell mass. TE, trophectoderm.
Figure 4
Figure 4
Significantly enriched gene sets (FDR A). Pie charts showing the enriched gene sets in HI ICM versus CNTRL ICM. (B). Pie charts showing the enriched gene sets in HI TE versus CNTRL TE. ICM, inner cell mass. TE, trophectoderm.
Figure 5
Figure 5
Significantly enriched gene sets (FDR A). Pie charts showing the enriched gene sets in HG ICM versus CNTRL ICM. (B). Pie charts showing the enriched gene sets in HG TE versus CNTRL TE. ICM, inner cell mass. TE, trophectoderm.
Figure 6
Figure 6
Quantification of proliferating and apoptotic cells in the ICM and TE of in-vitro-developed blastocysts with CNTRL, HG, and HGI by EdU incorporation and TUNEL assays. (A) Barplots showing the emmeans of proliferating cells in the ICM (n ICM = 16–38). (B) Barplots showing the emmeans percentage of apoptotic cells in the ICM (n ICM = 13–59). (C) Barplots showing the emmeans of proliferating cells in the TE (n TE = 16–24). (D) Barplots showing the emmeans of apoptotic cells in the TE (n TE = 18–52). Values are presented as emmeans ± S.E. Significant p values (p < 0.05) are shown. ICM, inner cell mass. TE, trophectoderm; CNTRL, control; HG, high glucose; HGI, high glucose and high insulin.
Figure 7
Figure 7
Heatmap showing the differential expression of genes (DEG) implicated in the TE lineage in HG and HGI ICM compared to CNTRL ICM. The mean normalized expression counts of n = 3 biological replicates, transformed to a Z-score, are represented by the color key. The gray color indicates the gene is not a DEG in that group. ICM, inner cell mass. TE, trophectoderm.
Figure 8
Figure 8
Heatmap showing the differential expression of genes (DEG) with a role in epigenetic regulation in HG and HGI TE compared to CNTRL TE. The mean normalized expression counts of n = 3 biological replicates, transformed to a z-score, are represented by the color key. The gray color indicates that the gene is not a DEG in that group. ICM, inner cell mass. TE, trophectoderm.
Figure 9
Figure 9
Significantly enriched gene sets (FDR A). Pie charts showing the enriched gene sets in HGI ICM versus CNTRL ICM. (B). Pie charts showing the enriched gene sets in HGI TE versus CNTRL TE. ICM, inner cell mass. TE, trophectoderm.

References

    1. InteInternational Diabetes Federation . IDF Diabetes Atlas. 10th ed. International Diabetes Federation; Brussels, Belgium: 2021.
    1. Thomas D.D., Corkey B.E., Istfan N.W., Apovian C.M. Hyperinsulinemia: An Early Indicator of Metabolic Dysfunction. J. Endocr. Soc. 2019;3:1727–1747. doi: 10.1210/js.2019-00065.
    1. Hjort L., Novakovic B., Grunnet L.G., Maple-Brown L., Damm P., Desoye G., Saffery R. Diabetes in Pregnancy and Epigenetic Mechanisms—How the First 9 Months from Conception Might Affect the Child’s Epigenome and Later Risk of Disease. Lancet Diabetes Endocrinol. 2019;7:796–806. doi: 10.1016/S2213-8587(19)30078-6.
    1. DiMeglio L.A., Evans-Molina C., Oram R.A. Type 1 Diabetes. Lancet. 2018;391:2449–2462. doi: 10.1016/S0140-6736(18)31320-5.
    1. Francis E.C., Dabelea D., Ringham B.M., Sauder K.A., Perng W. Maternal Blood Glucose Level and Offspring Glucose–Insulin Homeostasis: What Is the Role of Offspring Adiposity? Diabetologia. 2020;64:83–94. doi: 10.1007/s00125-020-05294-2.
    1. Langley-Evans S.C. Nutrition in Early Life and the Programming of Adult Disease: A Review. J. Hum. Nutr. Diet. 2015;28:1–14. doi: 10.1111/jhn.12212.
    1. Watkins A.J., Ursell E., Panton R., Papenbrock T., Hollis L., Cunningham C., Wilkins A., Perry V.H., Sheth B., Kwong W.Y., et al. Adaptive Responses by Mouse Early Embryos to Maternal Diet Protect Fetal Growth but Predispose to Adult Onset Disease1. Biol. Reprod. 2007;78:299–306. doi: 10.1095/biolreprod.107.064220.
    1. Velazquez M.A. Impact of Maternal Malnutrition during the Periconceptional Period on Mammalian Preimplantation Embryo Development. Domest. Anim. Endocrinol. 2015;51:27–45. doi: 10.1016/j.domaniend.2014.10.003.
    1. Kaye P.L., Gardner H.G. Preimplantation Access to Maternal Insulin and Albumin Increases Fetal Growth Rate in Mice. Hum. Reprod. 1999;14:3052–3059. doi: 10.1093/humrep/14.12.3052.
    1. Acevedo J.J., Mendoza-Lujambio I., de la Vega-Beltrán J.L., Treviño C.L., Felix R., Darszon A. KATP Channels in Mouse Spermatogenic Cells and Sperm, and Their Role in Capacitation. Dev. Biol. 2006;289:395–405. doi: 10.1016/j.ydbio.2005.11.002.
    1. Fraser R.B., Waite S.L., Wood K.A., Martin K.L. Impact of Hyperglycemia on Early Embryo Development and Embryopathy: In Vitro Experiments Using a Mouse Model. Hum. Reprod. 2007;22:3059–3068. doi: 10.1093/humrep/dem318.
    1. Fleming T.P., Sun C., Denisenko O., Caetano L., Aljahdali A., Gould J.M., Khurana P. Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk. Int. J. Environ. Res. Public Health. 2021;18:9380. doi: 10.3390/ijerph18179380.
    1. Jungheim E.S., Moley K.H. The Impact of Type 1 and Type 2 Diabetes Mellitus on the Oocyte and the Preimplantation Embryo. Semin. Reprod. Med. 2008;26:186–195. doi: 10.1055/s-2008-1042957.
    1. Ramin N., Thieme R., Fischer S., Schindler M., Schmidt T., Fischer B., Santos A.N. Maternal Diabetes Impairs Gastrulation and Insulin and IGF-I Receptor Expression in Rabbit Blastocysts. Endocrinology. 2010;151:4158–4167. doi: 10.1210/en.2010-0187.
    1. Rousseau-Ralliard D., Couturier-Tarrade A., Thieme R., Brat R., Rolland A., Boileau P., Aubrière M.-C., Daniel N., Dahirel M., Derisoud E., et al. A Short Periconceptional Exposure to Maternal Type-1 Diabetes Is Sufficient to Disrupt the Feto-Placental Phenotype in a Rabbit Model. Mol. Cell. Endocrinol. 2019;480:42–53. doi: 10.1016/j.mce.2018.10.010.
    1. Moley K.H., Chi M.M.Y.M.-Y., Mueckler M.M. Maternal Hyperglycemia Alters Glucose Transport and Utilization in Mouse Preimplantation Embryos. Am. J. Physiol. Metab. 1998;275:E38–E47. doi: 10.1152/ajpendo.1998.275.1.E38.
    1. Leunda-Casi A., de Hertogh R., Pampfer S. Decreased Expression of Fibroblast Growth Factor-4 and Associated Dysregulation of Trophoblast Differentiation in Mouse Blastocysts Exposed to High D-Glucose in Vitro. Diabetologia. 2001;44:1318–1325. doi: 10.1007/s001250100633.
    1. Boucher J., Kleinridders A., Kahn C.R. Insulin Receptor Signaling in Normal and Insulin-Resistant States. Cold Spring Harb. Perspect. Biol. 2014;6:a009191. doi: 10.1101/cshperspect.a009191.
    1. Purcell S.H., Moley K.H. Glucose Transporters in Gametes and Preimplantation Embryos. Trends Endocrinol. Metab. 2009;20:483–489. doi: 10.1016/j.tem.2009.06.006.
    1. Gardner D.K., Harvey A.J. Blastocyst Metabolism. Reprod. Fertil. Dev. 2015;27:638–654. doi: 10.1071/RD14421.
    1. Navarrete Santos A., Ramin N., Tonack S., Fischer B. Cell Lineage-Specific Signaling of Insulin and Insulin-Like Growth Factor I in Rabbit Blastocysts. Endocrinology. 2008;149:515–524. doi: 10.1210/en.2007-0821.
    1. Canon E., Jouneau L., Blachère T., Peynot N., Daniel N., Boulanger L., Maulny L., Archilla C., Voisin S., Jouneau A., et al. Progressive Methylation of POU5F1 Regulatory Regions during Blastocyst Development. Reproduction. 2018;156:145–161. doi: 10.1530/REP-17-0689.
    1. Bouchereau W., Jouneau L., Archilla C., Aksoy I., Moulin A., Daniel N., Peynot N., Calderari S., Joly T., Godet M., et al. Major Transcriptomic, Epigenetic and Metabolic Changes Underlie the Pluripotency Continuum in Rabbit Preimplantation Embryos. Development. 2022;149:dev200538. doi: 10.1242/dev.200538.
    1. Fleming T.P., Kwong W.Y., Porter R., Ursell E., Fesenko I., Wilkins A., Miller D.J., Watkins A.J., Eckert J.J. The Embryo and Its Future. Biol. Reprod. 2004;71:1046–1054. doi: 10.1095/biolreprod.104.030957.
    1. Staud F., Karahoda R. Trophoblast: The Central Unit of Fetal Growth, Protection and Programming. Int. J. Biochem. Cell Biol. 2018;105:35–40. doi: 10.1016/j.biocel.2018.09.016.
    1. Fischer B., Chavatte-Palmer P., Viebahn C., Navarrete Santos A., Duranthon V. Rabbit as a Reproductive Model for Human Health. Reproduction. 2012;144:1–10. doi: 10.1530/REP-12-0091.
    1. Laskowski D., Sjunnesson Y., Humblot P., Sirard M.A., Andersson G., Gustafsson H., Båge R. Insulin Exposure during in Vitro Bovine Oocyte Maturation Changes Blastocyst Gene Expression and Developmental Potential. Reprod. Fertil. Dev. 2017;29:876–889. doi: 10.1071/RD15315.
    1. Tarrade A., Rousseau-Ralliard D., Aubrière M.C., Peynot N., Dahirel M., Bertrand-Michel J., Aguirre-Lavin T., Morel O., Beaujean N., Duranthon V., et al. Sexual Dimorphism of the Feto-Placental Phenotype in Response to a High Fat and Control Maternal Diets in a Rabbit Model. PLoS ONE. 2013;8:e83458. doi: 10.1371/journal.pone.0083458.
    1. Sanz G., Daniel N., Aubrière M.C., Archilla C., Jouneau L., Jaszczyszyn Y., Duranthon V., Chavatte-Palmer P., Jouneau A. Differentiation of Derived Rabbit Trophoblast Stem Cells under Fluid Shear Stress to Mimic the Trophoblastic Barrier. Biochim. Biophys. Acta-Gen. Subj. 2019;1863:1608–1618. doi: 10.1016/j.bbagen.2019.07.003.
    1. Love M.I., Huber W., Anders S. Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2. Genome Biol. 2014;15:1–21. doi: 10.1186/s13059-014-0550-8.
    1. Heberle H., Meirelles V.G., da Silva F.R., Telles G.P., Minghim R. InteractiVenn: A Web-Based Tool for the Analysis of Sets through Venn Diagrams. BMC Bioinform. 2015;16:1–7. doi: 10.1186/s12859-015-0611-3.
    1. Huang D.W., Sherman B.T., Lempicki R.A. Systematic and Integrative Analysis of Large Gene Lists Using DAVID Bioinformatics Resources. Nat. Protoc. 2009;4:44–57. doi: 10.1038/nprot.2008.211.
    1. Subramanian A., Tamayo P., Mootha V.K., Mukherjee S., Ebert B.L., Gillette M.A., Paulovich A., Pomeroy S.L., Golub T.R., Lander E.S., et al. Gene Set Enrichment Analysis: A Knowledge-Based Approach for Interpreting Genome-Wide Expression Profiles. Proc. Natl. Acad. Sci. USA. 2005;102:15545–15550. doi: 10.1073/pnas.0506580102.
    1. Liberzon A., Birger C., Thorvaldsdóttir H., Ghandi M., Mesirov J.P., Tamayo P. The Molecular Signatures Database Hallmark Gene Set Collection. Cell Syst. 2015;1:417–425. doi: 10.1016/j.cels.2015.12.004.
    1. Jassal B., Matthews L., Viteri G., Gong C., Lorente P., Fabregat A., Sidiropoulos K., Cook J., Gillespie M., Haw R., et al. The Reactome Pathway Knowledgebase. Nucleic Acids Res. 2019;48:D498–D503. doi: 10.1093/nar/gkz1031.
    1. Ashburner M., Ball C.A., Blake J.A., Botstein D., Butler H., Cherry J.M., Davis A.P., Dolinski K., Dwight S.S., Eppig J.T., et al. Gene Ontology: Tool for the Unification of Biology. Nat. Genet. 2000;25:25–29. doi: 10.1038/75556.
    1. Carbon S., Douglass E., Good B.M., Unni D.R., Harris N.L., Mungall C.J., Basu S., Chisholm R.L., Dodson R.J., Hartline E., et al. The Gene Ontology Resource: Enriching a GOld Mine. Nucleic Acids Res. 2021;49:D325–D334. doi: 10.1093/nar/gkaa1113.
    1. Savage S.R., Shi Z., Liao Y., Zhang B. Graph Algorithms for Condensing and Consolidating Gene Set Analysis Results. Mol. Cell. Proteomics. 2019;18:S141–S152. doi: 10.1074/mcp.TIR118.001263.
    1. Morris J.H., Apeltsin L., Newman A.M., Baumbach J., Wittkop T., Su G., Bader G.D., Ferrin T.E. ClusterMaker: A Multi-Algorithm Clustering Plugin for Cytoscape. BMC Bioinform. 2011;12:1–14. doi: 10.1186/1471-2105-12-436.
    1. Shannon P. Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks. Genome Res. 2003;13:2498–2504. doi: 10.1101/gr.1239303.
    1. Gürke J., Schindler M., Pendzialek S.M., Thieme R., Grybel K.J., Heller R., Spengler K., Fleming T.P., Fischer B., Navarrete Santos A. Maternal Diabetes Promotes MTORC1 Downstream Signalling in Rabbit Preimplantation Embryos. Reproduction. 2016;151:465–476. doi: 10.1530/REP-15-0523.
    1. Shao W.-J., Tao L.-Y., Xie J.-Y., Gao C., Hu J.-H., Zhao R.-Q. Exposure of Preimplantation Embryos to Insulin Alters Expression of Imprinted Genes. Comp. Med. 2007;57:482–486.
    1. Schindler M., Pendzialek S.M., Grybel K., Seeling T., Santos A.N. Metabolic Profiling in Blastocoel Fluid and Blood Plasma of Diabetic Rabbits. Int. J. Mol. Sci. 2020;21:919. doi: 10.3390/ijms21030919.
    1. Jiménez A., Madrid-Bury N., Fernández R., Pérez-Garnelo S., Moreira P., Pintado B., de la Fuente J., Gutiérrez-Adán A. Hyperglycemia-Induced Apoptosis Affects Sex Ratio of Bovine and Murine Preimplantation Embryos. Mol. Reprod. Dev. 2003;65:180–187. doi: 10.1002/mrd.10286.
    1. Moley K.H. Diabetes and Preimplantation Events of Embryogenesis. Semin. Reprod. Endocrinol. 1999;17:137–151. doi: 10.1055/s-2007-1016221.
    1. Pampfer S. Apoptosis in Rodent Peri-Implantation Embryos: Differential Susceptibility of Inner Cell Mass and Trophectoderm Cell Lineages—A Review. Placenta. 2000;21:3–10. doi: 10.1053/plac.1999.0519.
    1. Harvey M.B., Kaye P.L. Insulin Increases the Cell Number of the Inner Cell Mass and Stimulates Morphological Development of Mouse Blastocysts in Vitro. Development. 1990;110:963–967. doi: 10.1242/dev.110.3.963.
    1. Gardner H.G., Kaye P.L. Insulin Increases Cell Numbers and Morphological Development in Mouse Pre-Implantation Embryos in Vitro. Reprod. Fertil. Dev. 1991;3:79–91. doi: 10.1071/RD9910079.
    1. Augustin R., Pocar P., Wrenzycki C., Niemann H., Fischer B. Mitogenic and Anti-Apoptotic Activity of Insulin on Bovine Embryos Produced in Vitro. Reproduction. 2003;126:91–99. doi: 10.1530/rep.0.1260091.
    1. Chi M.M.-Y., Schlein A.L., Moley K.H. High Insulin-Like Growth Factor 1 (IGF-1) and Insulin Concentrations Trigger Apoptosis in the Mouse Blastocyst via Down-Regulation of the IGF-1 Receptor. Endocrinology. 2000;141:4784–4792. doi: 10.1210/endo.141.12.7816.
    1. Kaneko K.J. Metabolism of Preimplantation Embryo Development: A Bystander or an Active Participant? 1st ed. Volume 120. Elsevier Inc.; Amsterdam, The Netherlands: 2016.
    1. May-Panloup P., Boguenet M., El Hachem H., Bouet P.E., Reynier P. Embryo and Its Mitochondria. Antioxidants. 2021;10:139. doi: 10.3390/antiox10020139.
    1. Leese H.J., Conaghan J., Martin K.L., Hardy K. Early Human Embryo Metabolism. BioEssays. 1993;15:259–264. doi: 10.1002/bies.950150406.
    1. Liu G.Y., Sabatini D.M. MTOR at the Nexus of Nutrition, Growth, Ageing and Disease. Nat. Rev. Mol. Cell Biol. 2020;8:183–203. doi: 10.1038/s41580-019-0199-y.
    1. Cheng Z., Tseng Y., White M.F. Insulin Signaling Meets Mitochondria in Metabolism. Trends Endocrinol. Metab. 2010;21:589–598. doi: 10.1016/j.tem.2010.06.005.
    1. Sies H., Jones D.P. Reactive Oxygen Species (ROS) as Pleiotropic Physiological Signalling Agents. Nat. Rev. Mol. Cell Biol. 2020;21:363–383. doi: 10.1038/s41580-020-0230-3.
    1. Albensi B.C. What Is Nuclear Factor Kappa B (NF-ΚB) Doing in and to the Mitochondrion? Front. Cell Dev. Biol. 2019;7:154. doi: 10.3389/fcell.2019.00154.
    1. Bertrand F., Philippe C., Antoine P.J., Baud L., Groyer A., Capeau J., Cherqui G. Insulin Activates Nuclear Factor ΚB in Mammalian Cells through a Raf-1- Mediated Pathway. J. Biol. Chem. 1995;270:24435–24441. doi: 10.1074/jbc.270.41.24435.
    1. Morgan M.J., Liu Z. Crosstalk of Reactive Oxygen Species and NF-ΚB Signaling. Cell Res. 2011;21:103–115. doi: 10.1038/cr.2010.178.
    1. Reid M.A., Dai Z., Locasale J.W. The Impact of Cellular Metabolism on Chromatin Dynamics and Epigenetics. Nat. Cell Biol. 2017;19:1298–1306. doi: 10.1038/ncb3629.
    1. Martínez-Reyes I., Chandel N.S. Mitochondrial TCA Cycle Metabolites Control Physiology and Disease. Nat. Commun. 2020;11:102. doi: 10.1038/s41467-019-13668-3.
    1. Arab K., Karaulanov E., Musheev M., Trnka P., Schäfer A., Grummt I., Niehrs C. GADD45A Binds R-Loops and Recruits TET1 to CpG Island Promoters. Nat. Genet. 2019;51:217–223. doi: 10.1038/s41588-018-0306-6.
    1. Qian X., Zhang Y. EZH2 Enhances Proliferation and Migration of Trophoblast Cell Lines by Blocking GADD45A-Mediated P38/MAPK Signaling Pathway. Bioengineered. 2022;13:12583–12597. doi: 10.1080/21655979.2022.2074620.
    1. Goller T., Vauti F., Ramasamy S., Arnold H.-H. Transcriptional Regulator BPTF/FAC1 Is Essential for Trophoblast Differentiation during Early Mouse Development. Mol. Cell. Biol. 2008;28:6819–6827. doi: 10.1128/MCB.01058-08.
    1. Landry J., Sharov A.A., Piao Y., Sharova L.V., Xiao H., Southon E., Matta J., Tessarollo L., Zhang Y.E., Ko M.S.H., et al. Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells. PLoS Genet. 2008;4:e1000241. doi: 10.1371/journal.pgen.1000241.
    1. Beato M., Sharma P. Peptidyl Arginine Deiminase 2 (PADI2)-Mediated Arginine Citrullination Modulates Transcription in Cancer. Int. J. Mol. Sci. 2020;21:1351. doi: 10.3390/ijms21041351.
    1. Yoshida K., Maekawa T., Ly N.H., Fujita S., Muratani M., Ando M., Katou Y., Araki H., Miura F., Shirahige K., et al. ATF7-Dependent Epigenetic Changes are Required for the Intergenerational Effect of a Paternal Low-Protein Diet. Mol. Cell. 2020;78:445–458.e6. doi: 10.1016/j.molcel.2020.02.028.
    1. Liu Y., Maekawa T., Yoshida K., Muratani M., Chatton B., Ishii S. The Transcription Factor ATF7 Controls Adipocyte Differentiation and Thermogenic Gene Programming. iScience. 2019;13:98–112. doi: 10.1016/j.isci.2019.02.013.
    1. Ralston A., Cox B.J., Nishioka N., Sasaki H., Chea E., Rugg-Gunn P., Guo G., Robson P., Draper J.S., Rossant J. Gata3 Regulates Trophoblast Development Downstream of Tead4 and in Parallel to Cdx2. Development. 2010;137:395–403. doi: 10.1242/dev.038828.
    1. Chi F., Sharpley M.S., Nagaraj R., Roy S.S., Banerjee U. Glycolysis-Independent Glucose Metabolism Distinguishes TE from ICM Fate during Mammalian Embryogenesis. Dev. Cell. 2020;53:9–26.e4. doi: 10.1016/j.devcel.2020.02.015.
    1. Murray A., Sienerth A.R., Hemberger M. Plet1 Is an Epigenetically Regulated Cell Surface Protein That Provides Essential Cues to Direct Trophoblast Stem Cell Differentiation. Sci. Rep. 2016;6:25112. doi: 10.1038/srep25112.
    1. Ono R., Nakamura K., Inoue K., Naruse M., Usami T., Wakisaka-Saito N., Hino T., Suzuki-Migishima R., Ogonuki N., Miki H., et al. Deletion of Peg10, an Imprinted Gene Acquired from a Retrotransposon, Causes Early Embryonic Lethality. Nat. Genet. 2006;38:101–106. doi: 10.1038/ng1699.
    1. Chen A.C.H., Lee Y.L., Fong S.W., Wong C.C.Y., Ng E.H.Y., Yeung W.S.B. Hyperglycemia Impedes Definitive Endoderm Differentiation of Human Embryonic Stem Cells by Modulating Histone Methylation Patterns. Cell Tissue Res. 2017;368:563–578. doi: 10.1007/s00441-017-2583-2.
    1. Armistead B., Kadam L., Drewlo S., Kohan-Ghadr H.-R.R. The Role of NFκB in Healthy and Preeclamptic Placenta: Trophoblasts in the Spotlight. Int. J. Mol. Sci. 2020;21:1775. doi: 10.3390/ijms21051775.
    1. Marchand M., Horcajadas J.A., Esteban F.J., McElroy S.L., Fisher S.J., Giudice L.C. Transcriptomic Signature of Trophoblast Differentiation in a Human Embryonic Stem Cell Model. Biol. Reprod. 2011;84:1258–1271. doi: 10.1095/biolreprod.110.086413.
    1. Ansell J.D., Snow M.H.L. The Development of Trophoblast in Vitro from Blastocysts Containing Varying Amounts of Inner Cell Mass. J. Embryol. Exp. Morphol. 1975;33:177–185. doi: 10.1242/dev.33.1.177.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren