{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:01Z","timestamp":1785437941767,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"French Institute of Health and Medical Research","award":["none"],"award-info":[{"award-number":["none"]}]},{"award":["none"],"award-info":[{"award-number":["none"]}],"id":[{"id":"https:\/\/ror.org\/02vjkv261","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Universit\u00e9 Paris-Cit\u00e9","award":["none"],"award-info":[{"award-number":["none"]}]},{"award":["none"],"award-info":[{"award-number":["none"]}],"id":[{"id":"https:\/\/ror.org\/05f82e368","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3), encoded by the PPARG gene on chromosome 3p25.2 in humans, is a ligand-dependent transcription factor that belongs to the nuclear receptor family. In various tissues, PPAR\u03b3 controls cell differentiation, proliferation, or fusion. Its essential role in the development and functions of the placenta is now well established. To date, the specific functions of its RNA isoforms, encoded by ten exons, in trophoblast biology, including cell fusion and invasion, remain unknown. As translation is mainly regulated by the 5\u2032UTR sequences of mature mRNA, this region was analyzed, and four previously unreported exonic sequences were revealed. Their expressions were confirmed and quantified in villous cytotrophoblasts from term placenta and in chorionic villi from both first-trimester and term placenta. Distinct expression patterns were observed: one exon showed weak expression in placental and chorionic cells, another exhibited stable expression throughout pregnancy, while two exons specific to villous cytotrophoblasts displayed increased expression during the first trimester, suggesting a role in oxygen-responsive mechanisms. Among these, one may be involved in villous trophoblast differentiation. These findings demonstrate that the PPARG gene is composed of 14 exons and is highly regulated depending on cell type and the stage of cell differentiation.<\/jats:p>","DOI":"10.3390\/cells15070639","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T15:14:43Z","timestamp":1775142883000},"page":"639","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["New PPARG Exons: Cell-Specific Expression of Their RNAs in the Human Placenta"],"prefix":"10.3390","volume":"15","author":[{"given":"Marie-L\u00e9one","family":"Vignaud","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, UMR-S1139, FPRM, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Morin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, UMR-S1139, FPRM, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Fournier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Inserm, UMR-S1139, FPRM, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jri.2011.05.003","article-title":"PPAR\u03b3 and Human Trophoblast Differentiation","volume":"90","author":"Fournier","year":"2011","journal-title":"J. Reprod. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hernandez-Quiles, M., Broekema, M.F., and Kalkhoven, E. (2021). PPARgamma in Metabolism, Immunity, and Cancer: Unified and Diverse Mechanisms of Action. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.624112"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.cell.2005.11.026","article-title":"The Many Faces of PPAR\u03b3","volume":"123","author":"Lehrke","year":"2005","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3109\/19396368.2014.991881","article-title":"The Balancing Act\u2014PPAR-\u03b3\u2019s Roles at the Maternal-Fetal Interface","volume":"61","author":"Kadam","year":"2015","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4583","DOI":"10.1210\/en.2003-1747","article-title":"Lipids from Oxidized Low-Density Lipoprotein Modulate Human Trophoblast Invasion: Involvement of Nuclear Liver X Receptors","volume":"145","author":"Pavan","year":"2004","journal-title":"Endocrinology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S1097-2765(00)80209-9","article-title":"PPAR \u03b3 Is Required for Placental, Cardiac, and Adipose Tissue Development","volume":"4","author":"Barak","year":"1999","journal-title":"Mol. Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"142082","DOI":"10.1155\/2008\/142082","article-title":"PPAR Signaling in Placental Development and Function","volume":"2008","author":"Barak","year":"2008","journal-title":"PPAR Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4969","DOI":"10.1210\/en.2010-0131","article-title":"PPAR\u03b3 in Placental Angiogenesis","volume":"151","author":"Nadra","year":"2010","journal-title":"Endocrinology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S1097-2765(00)80210-5","article-title":"PPAR \u03b3 Mediates High-Fat Diet-Induced Adipocyte Hypertrophy and Insulin Resistance","volume":"4","author":"Kubota","year":"1999","journal-title":"Mol. Cell"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Peng, L., Yang, H., Ye, Y., Ma, Z., Kuhn, C., Rahmeh, M., Mahner, S., Makrigiannakis, A., Jeschke, U., and von Sch\u00f6nfeldt, V. (2021). Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Trophoblast Functions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010433"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"527048","DOI":"10.1155\/2008\/527048","article-title":"PPAR Action in Human Placental Development and Pregnancy and Its Complications","volume":"2008","author":"Wieser","year":"2008","journal-title":"PPAR Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/ejendo\/lvad023","article-title":"Perinatal, Metabolic, and Reproductive Features in PPARG-Related Lipodystrophy","volume":"188","author":"Gosseaume","year":"2023","journal-title":"Eur. J. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s10456-005-9027-4","article-title":"PPAR Gamma Represses VEGF Expression in Human Endometrial Cells: Implications for Uterine Angiogenesis","volume":"8","author":"Peeters","year":"2005","journal-title":"Angiogenesis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e398","DOI":"10.1111\/j.1464-5491.2012.03742.x","article-title":"A Complicated Pregnancy in a Patient with Lipodystrophic Diabetes Attributable to a Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Mutation","volume":"29","author":"Madhra","year":"2012","journal-title":"Diabet. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1439-0388.2005.00508.x","article-title":"Identification and Characterization of Novel Peroxisome Proliferator-Activated Receptor-Gamma (PPAR-\u03b3) Transcriptional Variants in Pig and Human","volume":"122","author":"Omi","year":"2005","journal-title":"J. Anim. Breed. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bbaexp.2006.01.005","article-title":"Identification and Regulation of Novel PPAR-\u03b3 Splice Variants in Human THP-1 Macrophages","volume":"1759","author":"Chen","year":"2006","journal-title":"Biochim. Biophys. Acta (BBA)-Gene Struct. Expr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1006\/bbrc.1997.7564","article-title":"Characterisation of Bovine Peroxisome Proliferator-Activated Receptors \u03b31 and \u03b32: Genetic Mapping and Differential Expression of the Two Isoforms","volume":"239","author":"Sundvold","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1006\/bbrc.2001.5602","article-title":"Identification of a Novel Peroxisome Proliferator-Activated Receptor (PPAR) \u03b3 Promoter in Man and Transactivation by the Nuclear Receptor ROR\u03b11","volume":"287","author":"Sundvold","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/bies.201600095","article-title":"Is H3K4me3 Instructive for Transcription Activation?","volume":"39","author":"Howe","year":"2017","journal-title":"Bioessays"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of Chromatin by Histone Modifications","volume":"21","author":"Bannister","year":"2011","journal-title":"Cell Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21931","DOI":"10.1073\/pnas.1016071107","article-title":"Histone H3K27ac Separates Active from Poised Enhancers and Predicts Developmental State","volume":"107","author":"Creyghton","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Deval, G., Nedder, M., Degrelle, S., Rogozarski, J., Vignaud, M.-L., Chissey, A., Colzin, S., Laguillier-Morizot, C., Coumoul, X., and Boland, S. (2023). Benzo(a)Pyrene and Cerium Dioxide Nanoparticles in Co-Exposure Impair Human Trophoblast Cell Stress Signaling. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065439"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1007\/s00018-022-04491-z","article-title":"Evolution and Molecular Interactions of Major Histocompatibility Complex (MHC)-G, -E and -F Genes","volume":"79","author":"Juarez","year":"2022","journal-title":"Cell Mol. Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.placenta.2017.12.001","article-title":"Fetal-Sex Determination of Human Placental Tissues","volume":"61","author":"Degrelle","year":"2018","journal-title":"Placenta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/nrg2957","article-title":"Enhancer Function: New Insights into the Regulation of Tissue-Specific Gene Expression","volume":"12","author":"Ong","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12958-015-0070-8","article-title":"Isolation, Purification and in Vitro Differentiation of Cytotrophoblast Cells from Human Term Placenta","volume":"13","author":"Li","year":"2015","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e09691","DOI":"10.1002\/advs.202509691","article-title":"Decoding Human Placental Cellular and Molecular Responses to Maternal Obesity and Fetal Growth","volume":"13","author":"Jiang","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jim.2003.03.001","article-title":"Evaluation of Cytokeratin 7 as an Accurate Intracellular Marker with Which to Assess the Purity of Human Placental Villous Trophoblast Cells by Flow Cytometry","volume":"286","author":"Menu","year":"2004","journal-title":"J. Immunol. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103985","DOI":"10.1016\/j.jri.2023.103985","article-title":"Placental Physioxia Is Based on Spatial and Temporal Variations of Placental Oxygenation Throughout Pregnancy","volume":"158","author":"Huppertz","year":"2023","journal-title":"J. Reprod. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1016\/S0002-9440(10)64849-3","article-title":"Onset of Maternal Arterial Blood Flow and Placental Oxidative Stress. A Possible Factor in Human Early Pregnancy Failure","volume":"157","author":"Jauniaux","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_31","first-page":"283","article-title":"Oxygen Measurements in Endometrial and Trophoblastic Tissues During Early Pregnancy","volume":"80","author":"Rodesch","year":"1992","journal-title":"Obstet. Gynecol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.7150\/ijbs.73616","article-title":"Human Leukocyte Antigens: The Unique Expression in Trophoblasts and Their Crosstalk with Local Immune Cells","volume":"18","author":"Lin","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1182\/blood.V75.12.2417.2417","article-title":"Expression of the CD34 Gene in Vascular Endothelial Cells","volume":"75","author":"Fina","year":"1990","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/wrr.12920","article-title":"Vimentin Regulates the Assembly and Function of Matrix Adhesions","volume":"29","author":"McCulloch","year":"2021","journal-title":"Wound Repair Regen."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13293-024-00629-9","article-title":"Sexually Dimorphic DNA Methylation and Gene Expression Patterns in Human First Trimester Placenta","volume":"15","author":"Gonzalez","year":"2024","journal-title":"Biol. Sex Differ."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1093\/biolre\/ioaf158","article-title":"Adverse Neonatal Outcomes Are Associated with a Sex-Specific Placental Inflammatory Profile\u2020","volume":"113","author":"Couture","year":"2025","journal-title":"Biol. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13293-024-00652-w","article-title":"Sex-Specific Phenotypical, Functional and Metabolic Profiles of Human Term Placenta Macrophages","volume":"15","author":"Paparini","year":"2024","journal-title":"Biol. Sex Differ."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.bbrc.2004.01.074","article-title":"Expression and Function of PPAR\u03b3 in Rat Placental Development","volume":"315","author":"Iseki","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_39","first-page":"5017","article-title":"PPAR\u03b3\/RXR\u03b1 Heterodimers Control Human Trophoblast Invasion","volume":"86","author":"Tarrade","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/j.celrep.2018.10.035","article-title":"PPAR\u03b3\u03945, a Naturally Occurring Dominant-Negative Splice Isoform, Impairs PPAR\u03b3 Function and Adipocyte Differentiation","volume":"25","author":"Aprile","year":"2018","journal-title":"Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bryant, C., Webb, A., Banks, A.S., Chandler, D., Govindarajan, R., and Agrawal, S. (2022). Alternatively Spliced Landscape of PPAR\u03b3 mRNA in Podocytes Is Distinct from Adipose Tissue. Cells, 11.","DOI":"10.1101\/2022.09.12.507605"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12650","DOI":"10.1038\/srep12650","article-title":"PPAR\u03b3 Stimulates Expression of L-Type Amino Acid and Taurine Transporters in Human Placentas: The Evidence of PPAR\u03b3 Regulating Fetal Growth","volume":"5","author":"Chen","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4504","DOI":"10.1210\/endo.142.10.8448","article-title":"PPAR \u03b3\/RXR \u03b1 Heterodimers Are Involved in Human CG \u03b2 Synthesis and Human Trophoblast Differentiation","volume":"142","author":"Tarrade","year":"2001","journal-title":"Endocrinology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"18779","DOI":"10.1074\/jbc.272.30.18779","article-title":"The Organization, Promoter Analysis, and Expression of the Human PPAR\u03b3 Gene","volume":"272","author":"Fajas","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0014-5793(98)01273-3","article-title":"PPAR\u03b33 mRNA: A Distinct PPAR\u03b3 mRNA Subtype Transcribed from an Independent Promoter","volume":"438","author":"Fajas","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S76","DOI":"10.1016\/j.placenta.2006.12.006","article-title":"Involvement of PPAR\u03b3 in Human Trophoblast Invasion","volume":"28","author":"Fournier","year":"2007","journal-title":"Placenta"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1210\/en.2008-0456","article-title":"Identification of Novel Trophoblast Invasion-Related Genes: Heme Oxygenase-1 Controls Motility via Peroxisome Proliferator-Activated Receptor \u03b3","volume":"150","author":"Bilban","year":"2009","journal-title":"Endocrinology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.placenta.2005.10.012","article-title":"Modulation of PAPP-A Expression by PPAR\u03b3 in Human First Trimester Trophoblast","volume":"27","author":"Handschuh","year":"2006","journal-title":"Placenta"},{"key":"ref_49","first-page":"1601","article-title":"Genetic Analysis of Peroxisome Proliferator-Activated Receptor \u03b31 Splice Variants in Human Colorectal Cell Lines","volume":"29","author":"Fiatte","year":"2006","journal-title":"Int. J. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ding, L., Jiang, H., Shen, L., and Xu, Y. (2025). The Role of PPAR\u03b3 in Cancer Cachexia: Friend or Foe?. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1717134"},{"key":"ref_51","first-page":"221","article-title":"Peroxisome Proliferators: A Model for Receptor Mediated Carcinogenesis","volume":"14","author":"Green","year":"1992","journal-title":"Cancer Surv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1002\/ijc.28432","article-title":"Loss of PPAR\u03b3 Expression in Mammary Secretory Epithelial Cells Creates a Pro-Breast Tumorigenic Environment","volume":"134","author":"Apostoli","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Simsek, D., Hassan, G.S., Sotgia, F., and Lisanti, M.P. (2025). Investigating the Role of Peroxisomes in Regulating Breast Cancer Stem Cell Mechanisms. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262311389"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Parejo-Alonso, B., Mascaraque, M., Royo-Garc\u00eda, A., and Sancho, P. (2025). The Emerging Role of Peroxisome Proliferator-Activated Receptors in Cancer Stemness. Cells, 14.","DOI":"10.3390\/cells14201610"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1093\/humupd\/dmaa018","article-title":"Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS) and Their Effects on the Ovary","volume":"26","author":"Ding","year":"2020","journal-title":"Hum. Reprod. Update"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Meister, S., Hahn, L., Beyer, S., Paul, C., Mitter, S., Kuhn, C., von Sch\u00f6nfeldt, V., Corradini, S., Sudan, K., and Schulz, C. (2021). Regulation of Epigenetic Modifications in the Placenta during Preeclampsia: PPAR\u03b3 Influences H3K4me3 and H3K9ac in Extravillous Trophoblast Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212469"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/7\/639\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T04:34:18Z","timestamp":1775277258000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/7\/639"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":56,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["cells15070639"],"URL":"https:\/\/doi.org\/10.3390\/cells15070639","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]}}}