{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T03:08:07Z","timestamp":1791083287466,"version":"4.1.0"},"reference-count":125,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Institute of Environmental Health Sciences","award":["P30 ES029067"],"award-info":[{"award-number":["P30 ES029067"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The increasing incidence of pregnancy complications, particularly gestational diabetes mellitus (GDM) and preeclampsia (PE), is a cause for concern, as they can result in serious health consequences for both mothers and infants. The pathogenesis of these complications is still not fully understood, although it is known that the pathologic placenta plays a crucial role. Studies have shown that PPAR\u03b3, a transcription factor involved in glucose and lipid metabolism, may have a critical role in the etiology of these complications. While PPAR\u03b3 agonists are FDA-approved drugs for Type 2 Diabetes Mellitus, their safety during pregnancy is not yet established. Nevertheless, there is growing evidence for the therapeutic potential of PPAR\u03b3 in the treatment of PE using mouse models and in cell cultures. This review aims to summarize the current understanding of the mechanism of PPAR\u03b3 in placental pathophysiology and to explore the possibility of using PPAR\u03b3 ligands as a treatment option for pregnancy complications. Overall, this topic is of great significance for improving maternal and fetal health outcomes and warrants further investigation.<\/jats:p>","DOI":"10.3390\/nu15112459","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T03:56:58Z","timestamp":1684987018000},"page":"2459","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Understanding PPAR\u03b3 and Its Agonists on Trophoblast Differentiation and Invasion: Potential Therapeutic Targets for Gestational Diabetes Mellitus and Preeclampsia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5198-4818","authenticated-orcid":false,"given":"Yushu","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Nutrition, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donalyn","family":"Bily","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Texas A&M University, College Station, TX 77843, USA"},{"name":"Department of Biology, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makayla","family":"Aguirre","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Texas A&M University, College Station, TX 77843, USA"},{"name":"Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linglin","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Texas A&M University, College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"ref_1","unstructured":"(2020). Trends in Pregnancy and Childbirth Complications in the U.S., Blue cross Blue Shield."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Psilopatis, I., Vrettou, K., Fleckenstein, F.N., and Theocharis, S. (2023). The Role of Peroxisome Proliferator-Activated Receptors in Preeclampsia. Cells, 12.","DOI":"10.3390\/cells12040647"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"McElwain, C.J., McCarthy, F.P., and McCarthy, C.M. (2021). Gestational Diabetes Mellitus and Maternal Immune Dysregulation: What We Know So Far. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22084261"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Plows, J.F., Stanley, J.L., Baker, P.N., Reynolds, C.M., and Vickers, M.H. (2018). The Pathophysiology of Gestational Diabetes Mellitus. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113342"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3389\/fendo.2020.00655","article-title":"Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health?","volume":"11","author":"McElwain","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Longhitano, E., Siligato, R., Torreggiani, M., Attini, R., Masturzo, B., Casula, V., Matarazzo, I., Cabiddu, G., Santoro, D., and Versino, E. (2022). The Hypertensive Disorders of Pregnancy: A Focus on Definitions for Clinical Nephrologists. J. Clin. Med., 11.","DOI":"10.3390\/jcm11123420"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1161\/HYPERTENSIONAHA.117.10803","article-title":"Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice","volume":"72","author":"Brown","year":"2018","journal-title":"Hypertension"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.1751-7176.2011.00440.x","article-title":"Hypertension complicating diabetic pregnancies: Pathophysiology, management, and controversies","volume":"13","author":"Sullivan","year":"2011","journal-title":"J. Clin. Hypertens."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1161\/HYPERTENSIONAHA.122.18730","article-title":"Peripartum and Long-Term Maternal Cardiovascular Health After Preeclampsia","volume":"80","author":"Giorgione","year":"2023","journal-title":"Hypertension"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"537865","DOI":"10.1155\/2014\/537865","article-title":"PPARG in Human Adipogenesis: Differential Contribution of Canonical Transcripts and Dominant Negative Isoforms","volume":"2014","author":"Aprile","year":"2014","journal-title":"PPAR Res."},{"key":"ref_11","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 PPARgamma gene","volume":"272","author":"Fajas","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1677\/joe.1.06667","article-title":"Peroxisome proliferator-activated receptors in reproductive tissues: From gametogenesis to parturition","volume":"189","author":"Froment","year":"2006","journal-title":"J. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1475-2891-13-17","article-title":"Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications\u2014A review","volume":"13","year":"2014","journal-title":"Nutr. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1042\/CS20080195","article-title":"PPARgamma and its ligands: Therapeutic implications in cardiovascular disease","volume":"116","author":"Villacorta","year":"2009","journal-title":"Clin. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.cell.2005.11.026","article-title":"The many faces of PPARgamma","volume":"123","author":"Lehrke","year":"2005","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.neuropharm.2015.11.020","article-title":"Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist is neuroprotective and stimulates PGC-1alpha expression and CREB phosphorylation in human dopaminergic neurons","volume":"102","author":"Makela","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5777","DOI":"10.1038\/s41598-017-05666-6","article-title":"Betulinic acid is a PPARgamma antagonist that improves glucose uptake, promotes osteogenesis and inhibits adipogenesis","volume":"7","author":"Brusotti","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1210\/me.2002-0036","article-title":"A new selective peroxisome proliferator-activated receptor gamma antagonist with antiobesity and antidiabetic activity","volume":"16","author":"Rieusset","year":"2002","journal-title":"Mol. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1517\/14728222.12.8.1049","article-title":"PPAR-gamma signaling pathway in placental development and function: A potential therapeutic target in the treatment of gestational diseases","volume":"12","author":"Giaginis","year":"2008","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/bs.acc.2018.02.007","article-title":"Adiponectin and Its Isoforms in Pathophysiology","volume":"85","author":"Heijboer","year":"2018","journal-title":"Adv. Clin. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6268","DOI":"10.1177\/0300060519870723","article-title":"Inhibition of PPARgamma by bisphenol A diglycidyl ether ameliorates dexamethasone-induced osteoporosis in a mouse model","volume":"47","author":"Wang","year":"2019","journal-title":"J. Int. Med. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16747","DOI":"10.1073\/pnas.0508081102","article-title":"The antiinflammatory effect of laminar flow: The role of PPARgamma, epoxyeicosatrienoic acids, and soluble epoxide hydrolase","volume":"102","author":"Liu","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/S1097-2765(01)00353-7","article-title":"A unique PPARgamma ligand with potent insulin-sensitizing yet weak adipogenic activity","volume":"8","author":"Rocchi","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_24","first-page":"1425","article-title":"A selective peroxisome proliferator-activated receptor-gamma (PPARgamma) modulator blocks adipocyte differentiation but stimulates glucose uptake in 3T3-L1 adipocytes","volume":"14","author":"Mukherjee","year":"2000","journal-title":"Mol. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7242030","DOI":"10.1155\/2019\/7242030","article-title":"15-Deoxy-\u2206-(12,14)-Prostaglandin J2 (15d-PGJ2), an Endogenous Ligand of PPAR-gamma: Function and Mechanism","volume":"2019","author":"Li","year":"2019","journal-title":"PPAR Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"936906","DOI":"10.1155\/2008\/936906","article-title":"The Development of INT131 as a Selective PPARgamma Modulator: Approach to a Safer Insulin Sensitizer","volume":"2008","author":"Higgins","year":"2008","journal-title":"PPAR Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1210\/endo.142.7.8254","article-title":"A novel potent antagonist of peroxisome proliferator-activated receptor gamma blocks adipocyte differentiation but does not revert the phenotype of terminally differentiated adipocytes","volume":"142","author":"Camp","year":"2001","journal-title":"Endocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.12659\/MSM.907578","article-title":"Effect of Hexadecyl Azelaoyl Phosphatidylcholine on Cardiomyocyte Apoptosis in Myocardial Ischemia-Reperfusion Injury: A Hypothesis","volume":"24","author":"Feng","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_29","first-page":"A119","article-title":"GI262570, A PPAR [Gamma] Agonist, Maintains Metabolic Improvements throughout 24 Hour Profiles In Type 2 Diabetic Patients","volume":"49","author":"Mydlow","year":"2000","journal-title":"Diabetes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"19649","DOI":"10.1074\/jbc.M200743200","article-title":"T0070907, a selective ligand for peroxisome proliferator-activated receptor gamma, functions as an antagonist of biochemical and cellular activities","volume":"277","author":"Lee","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.ejmech.2018.06.034","article-title":"Synthesis and biological evaluations of marine oxohexadecenoic acids: PPARalpha\/gamma dual agonism and anti-diabetic target gene effects","volume":"155","author":"Saether","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.2337\/db06-1734","article-title":"S 26948: A new specific peroxisome proliferator activated receptor gamma modulator with potent antidiabetes and antiatherogenic effects","volume":"56","author":"Carmona","year":"2007","journal-title":"Diabetes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1038\/sj.bjp.0705973","article-title":"GW9662, a potent antagonist of PPARgamma, inhibits growth of breast tumour cells and promotes the anticancer effects of the PPARgamma agonist rosiglitazone, independently of PPARgamma activation","volume":"143","author":"Seargent","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.bcp.2007.05.027","article-title":"13-Oxo-ODE is an endogenous ligand for PPARgamma in human colonic epithelial cells","volume":"74","author":"Altmann","year":"2007","journal-title":"Biochem. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1194\/jlr.M200127-JLR200","article-title":"AZ 242, a novel PPARalpha\/gamma agonist with beneficial effects on insulin resistance and carbohydrate and lipid metabolism in ob\/ob mice and obese Zucker rats","volume":"43","author":"Ljung","year":"2002","journal-title":"J. Lipid Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Leghmar, K., Cenac, N., Rolland, M., Martin, H., Rauwel, B., Bertrand-Michel, J., Le Faouder, P., Benard, M., Casper, C., and Davrinche, C. (2015). Cytomegalovirus Infection Triggers the Secretion of the PPARgamma Agonists 15-Hydroxyeicosatetraenoic Acid (15-HETE) and 13-Hydroxyoctadecadienoic Acid (13-HODE) in Human Cytotrophoblasts and Placental Cultures. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132627"},{"key":"ref_37","first-page":"1360","article-title":"The rexinoid LG100754 is a novel RXR:PPARgamma agonist and decreases glucose levels in vivo","volume":"15","author":"Cesario","year":"2001","journal-title":"Mol. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1007\/s00592-005-0176-0","article-title":"Treating the metabolic syndrome: Telmisartan as a peroxisome proliferator-activated receptor-gamma activator","volume":"42","author":"Kurtz","year":"2005","journal-title":"Acta Diabetol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1186\/1479-5876-11-229","article-title":"Cardiac protective effects of irbesartan via the PPAR-gamma signaling pathway in angiotensin-converting enzyme 2-deficient mice","volume":"11","author":"Zhang","year":"2013","journal-title":"J. Transl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1161\/01.CIR.0000126824.12785.B6","article-title":"Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease","volume":"109","author":"Tenenbaum","year":"2004","journal-title":"Circulation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.cell.2007.02.050","article-title":"Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors","volume":"129","author":"Schug","year":"2007","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1158\/1078-0432.CCR-0476-03","article-title":"RWJ-241947 (MCC-555), a unique peroxisome proliferator-activated receptor-gamma ligand with antitumor activity against human prostate cancer in vitro and in beige\/nude\/ X-linked immunodeficient mice and enhancement of apoptosis in myeloma cells induced by arsenic trioxide","volume":"10","author":"Kumagai","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"759","DOI":"10.2337\/diabetes.49.5.759","article-title":"A new thiazolidinedione, NC-2100, which is a weak PPAR-gamma activator, exhibits potent antidiabetic effects and induces uncoupling protein 1 in white adipose tissue of KKAy obese mice","volume":"49","author":"Fukui","year":"2000","journal-title":"Diabetes"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1016\/S0026-0495(99)90158-0","article-title":"Amelioration by KRP-297, a new thiazolidinedione, of impaired glucose uptake in skeletal muscle from obese insulin-resistant animals","volume":"48","author":"Murakami","year":"1999","journal-title":"Metabolism"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"154338","DOI":"10.1016\/j.metabol.2020.154338","article-title":"The role of peroxisome proliferator-activated receptors (PPAR) in immune responses","volume":"114","author":"Christofides","year":"2021","journal-title":"Metabolism"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"431763","DOI":"10.1155\/2008\/431763","article-title":"Peroxisome Proliferator-Activated Receptor-gamma Ligands: Potential Pharmacological Agents for Targeting the Angiogenesis Signaling Cascade in Cancer","volume":"2008","author":"Giaginis","year":"2008","journal-title":"PPAR Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103210","DOI":"10.1016\/j.jri.2020.103210","article-title":"Expression of trophoblast derived prostaglandin E2 receptor 2 (EP2) is reduced in patients with recurrent miscarriage and EP2 regulates cell proliferation and expression of inflammatory cytokines","volume":"142","author":"Peng","year":"2020","journal-title":"J. Reprod. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S1097-2765(00)80209-9","article-title":"PPAR gamma is required for placental, cardiac, and adipose tissue development","volume":"4","author":"Barak","year":"1999","journal-title":"Mol. Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1053\/plac.2002.0855","article-title":"Expression of PPAR and RXR isoforms in the developing rat and human term placentas","volume":"23","author":"Wang","year":"2002","journal-title":"Placenta"},{"key":"ref_50","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 Schonfeldt, V. (2021). Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Trophoblast Functions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010433"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"E1468","DOI":"10.1210\/jc.2012-1064","article-title":"Placental expression of peroxisome proliferator-activated receptor gamma (PPARgamma): Relation to placental and fetal growth","volume":"97","author":"Diaz","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1080\/19336918.2015.1083668","article-title":"ADAM12 and PAPP-A: Candidate regulators of trophoblast invasion and first trimester markers of healthy trophoblasts","volume":"10","author":"Christians","year":"2016","journal-title":"Cell. Adh Migr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S76","DOI":"10.1016\/j.placenta.2006.12.006","article-title":"Involvement of PPARgamma in human trophoblast invasion","volume":"28","author":"Fournier","year":"2007","journal-title":"Placenta"},{"key":"ref_54","first-page":"5017","article-title":"PPARgamma\/RXRalpha heterodimers control human trophoblast invasion","volume":"86","author":"Tarrade","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"S127","DOI":"10.1016\/j.placenta.2005.10.012","article-title":"Modulation of PAPP-A expression by PPARgamma in human first trimester trophoblast","volume":"27","author":"Handschuh","year":"2006","journal-title":"Placenta"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1507\/endocrj.EJ12-0241","article-title":"Improvement of insulin sensitivity promotes extravillous trophoblast cell migration stimulated by insulin-like growth factor-I","volume":"60","author":"Mayama","year":"2013","journal-title":"Endocr. J."},{"key":"ref_57","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 gamma","volume":"150","author":"Bilban","year":"2009","journal-title":"Endocrinology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"E357","DOI":"10.1152\/ajpendo.00093.2015","article-title":"PPARgamma controls pregnancy outcome through activation of EG-VEGF: New insights into the mechanism of placental development","volume":"309","author":"Garnier","year":"2015","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1038\/s41598-018-38336-2","article-title":"Rosiglitazone blocks first trimester in-vitro placental injury caused by NF-kappaB-mediated inflammation","volume":"9","author":"Kadam","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1080\/21655979.2021.2020468","article-title":"Interleukin-17 promotes proliferation, migration, and invasion of trophoblasts via regulating PPAR-gamma\/RXR-alpha\/Wnt signaling","volume":"13","author":"Zhang","year":"2022","journal-title":"Bioengineered"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7660","DOI":"10.1111\/jcmm.15401","article-title":"Peroxisome proliferator-activated receptor gamma-ligand-binding domain mutations associated with familial partial lipodystrophy type 3 disrupt human trophoblast fusion and fibroblast migration","volume":"24","author":"Shoaito","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"637251","DOI":"10.1155\/2014\/637251","article-title":"PPAR-gamma Regulates Trophoblast Differentiation in the BeWo Cell Model","volume":"2014","author":"Levytska","year":"2014","journal-title":"PPAR Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4504","DOI":"10.1210\/endo.142.10.8448","article-title":"PPAR gamma\/RXR alpha heterodimers are involved in human CG beta synthesis and human trophoblast differentiation","volume":"142","author":"Tarrade","year":"2001","journal-title":"Endocrinology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"A1077","DOI":"10.1096\/fasebj.20.5.A1077-c","article-title":"PPAR gamma is expressed and regulates placental development and trophoblast differentiation in both humans and mice","volume":"20","author":"Milstone","year":"2006","journal-title":"FASEB"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1016\/j.ajog.2004.05.009","article-title":"Troglitazone attenuates hypoxia-induced injury in cultured term human trophoblasts","volume":"191","author":"Elchalal","year":"2004","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1089\/scd.2012.0596","article-title":"Hypoxia and trophoblast differentiation: A key role for PPARgamma","volume":"22","author":"Tache","year":"2013","journal-title":"Stem Cells Dev."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Parast, M.M., Yu, H., Ciric, A., Salata, M.W., Davis, V., and Milstone, D.S. (2009). PPARgamma regulates trophoblast proliferation and promotes labyrinthine trilineage differentiation. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0008055"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Fox, R., Kitt, J., Leeson, P., Aye, C.Y.L., and Lewandowski, A.J. (2019). Preeclampsia: Risk Factors, Diagnosis, Management, and the Cardiovascular Impact on the Offspring. J. Clin. Med., 8.","DOI":"10.3390\/jcm8101625"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1161\/CIRCRESAHA.118.313276","article-title":"Preeclampsia: Pathophysiology, Challenges, and Perspectives","volume":"124","author":"Rana","year":"2019","journal-title":"Circ. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"214365","DOI":"10.1155\/2011\/214365","article-title":"Maternal preeclampsia and neonatal outcomes","volume":"2011","author":"Backes","year":"2011","journal-title":"J. Pregnancy"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1161\/HYPERTENSIONAHA.107.107607","article-title":"Placental origins of preeclampsia: Challenging the current hypothesis","volume":"51","author":"Huppertz","year":"2008","journal-title":"Hypertension"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jri.2019.07.004","article-title":"The two-stage placental model of preeclampsia: An update","volume":"134\u2013135","author":"Staff","year":"2019","journal-title":"J. Reprod. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1016\/j.placenta.2008.11.009","article-title":"The two stage model of preeclampsia: Variations on the theme","volume":"30","author":"Roberts","year":"2009","journal-title":"Placenta"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1053\/j.semperi.2014.03.005","article-title":"Pathophysiology of ischemic placental disease","volume":"38","author":"Roberts","year":"2014","journal-title":"Semin. Perinatol."},{"key":"ref_75","first-page":"771","article-title":"Correlations of MMP-9 and PPAR\u03b3 gene polymorphisms with occurrence of preeclampsia","volume":"26","author":"Jia","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.placenta.2009.12.009","article-title":"Peroxisome proliferator-activated receptors are altered in pathologies of the human placenta: Gestational diabetes mellitus, intrauterine growth restriction and preeclampsia","volume":"31","author":"Lim","year":"2010","journal-title":"Placenta"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1902\/jop.2016.150677","article-title":"Evidence linking the role of placental expressions of Peroxisome Proliferator-Activated Receptor-\u03b3 and Nuclear Factor-Kappa B in the pathogenesis of preeclampsia associated with periodontitis","volume":"87","author":"Mahendra","year":"2016","journal-title":"J. Periodontol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1161\/HYPERTENSIONAHA.121.17267","article-title":"Induction of the PPAR\u03b3 (Peroxisome Proliferator-Activated Receptor \u03b3)-GCM1 (Glial Cell Missing 1) Syncytialization Axis Reduces sFLT1 (Soluble fms-Like Tyrosine Kinase 1) in the Preeclamptic Placenta","volume":"78","author":"Armistead","year":"2021","journal-title":"Hypertension"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1210\/en.2013-1350","article-title":"Reduced expression of 11\u03b2-hydroxysteroid dehydrogenase type 2 in preeclamptic placentas is associated with decreased PPAR\u03b3 but increased PPAR\u03b1 expression","volume":"155","author":"He","year":"2014","journal-title":"Endocrinology"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Permadi, W., Mantilidewi, K.I., Khairani, A.F., Lantika, U.A., Ronosulistyo, A.R., and Bayuaji, H. (2020). Differences in expression of Peroxisome Proliferator-activated Receptor-gamma in early-onset preeclampsia and late-onset preeclampsia. BMC Res. Notes, 13.","DOI":"10.1186\/s13104-020-05029-x"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1414838","article-title":"Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia","volume":"374","author":"Zeisler","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"106127","DOI":"10.1016\/j.phrs.2022.106127","article-title":"Procyanidin B2 ameliorates endothelial dysfunction and impaired angiogenesis via the Nrf2\/PPARgamma\/sFlt-1 axis in preeclampsia","volume":"177","author":"Liu","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e3054","DOI":"10.1038\/cddis.2017.419","article-title":"ANGPTL4 mediates the protective role of PPAR\u03b3 activators in the pathogenesis of preeclampsia","volume":"8","author":"Liu","year":"2017","journal-title":"Cell. Death Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1002\/biof.1542","article-title":"The role of epigenetic changes in preeclampsia","volume":"45","author":"Kamrani","year":"2019","journal-title":"Biofactors"},{"key":"ref_85","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"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"R23","DOI":"10.1530\/REP-16-0014","article-title":"Recent progress towards understanding the role of DNA methylation in human placental development","volume":"152","author":"Mayne","year":"2016","journal-title":"Reproduction"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/humupd\/dmq052","article-title":"Epigenetics and the placenta","volume":"17","author":"Nelissen","year":"2011","journal-title":"Hum. Reprod. Update"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"H1","DOI":"10.1152\/ajpheart.00117.2012","article-title":"A model of preeclampsia in rats: The reduced uterine perfusion pressure (RUPP) model","volume":"303","author":"Li","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1161\/HYPERTENSIONAHA.111.172627","article-title":"Peroxisome proliferator-activated receptor-gamma as a potential therapeutic target in the treatment of preeclampsia","volume":"58","author":"McCarthy","year":"2011","journal-title":"Hypertension"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1177\/1933719118756746","article-title":"Aspirin ameliorates preeclampsia induced by a peroxisome proliferator-activated receptor antagonist","volume":"25","author":"Zhang","year":"2018","journal-title":"Reprod. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1161\/HYPERTENSIONAHA.111.179440","article-title":"Evidence implicating peroxisome proliferator-activated receptor-\u03b3 in the pathogenesis of preeclampsia","volume":"58","author":"McCarthy","year":"2011","journal-title":"Hypertension"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Guo, Y., Zhu, Y., Sun, Y., and Yang, H. (2022). The preventive effect of low-dose aspirin in a PPAR-\u03b3 antagonist treated mouse model of preeclampsia. BMC Pregnancy Childbirth, 22.","DOI":"10.1186\/s12884-022-04901-x"},{"key":"ref_93","unstructured":"(2023, May 11). National Center for Biotechnology Information. Angiotensin (1-7), Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Angiotensin-_1-7."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.abb.2019.07.006","article-title":"The ameliorative effect of angiotensin 1-7 on experimentally induced-preeclampsia in rats: Targeting the role of peroxisome proliferator-activated receptors gamma expression & asymmetric dimethylarginine","volume":"671","author":"Madi","year":"2019","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrendo.2012.96","article-title":"Gestational diabetes mellitus: Risks and management during and after pregnancy","volume":"8","author":"Buchanan","year":"2012","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1016\/j.ijgo.2008.11.025","article-title":"Future risk of diabetes in mother and child after gestational diabetes mellitus","volume":"104","author":"Damm","year":"2009","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11892-015-0579-4","article-title":"Preeclampsia and diabetes","volume":"15","author":"Weissgerber","year":"2015","journal-title":"Curr. Diab Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"831297","DOI":"10.3389\/fcvm.2022.831297","article-title":"Gestational Diabetes Mellitus and Preeclampsia: Correlation and Influencing Factors","volume":"9","author":"Yang","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_99","first-page":"151","article-title":"Gestational diabetes mellitus: Why screen and how to diagnose","volume":"14","author":"Karagiannis","year":"2010","journal-title":"Hippokratia"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"965","DOI":"10.52586\/5001","article-title":"Hyperglycemia results in significant pathophysiological changes of placental spiral artery remodeling and angiogenesis, further contributing to congenital defects","volume":"26","author":"Qin","year":"2021","journal-title":"Front. Biosci."},{"key":"ref_101","first-page":"321","article-title":"Placental-fetal glucose exchange and fetal glucose metabolism","volume":"117","author":"Hay","year":"2006","journal-title":"Trans. Am. Clin. Climatol. Assoc."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"h102","DOI":"10.1136\/bmj.h102","article-title":"Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: A systematic review and meta-analysis","volume":"350","author":"Balsells","year":"2015","journal-title":"BMJ"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Jamilian, M., Samimi, M., Mirhosseini, N., Afshar Ebrahimi, F., Aghadavod, E., Taghizadeh, M., and Asemi, Z. (2018). A Randomized Double-Blinded, Placebo-Controlled Trial Investigating the Effect of Fish Oil Supplementation on Gene Expression Related to Insulin Action, Blood Lipids, and Inflammation in Gestational Diabetes Mellitus-Fish Oil Supplementation and Gestational Diabetes. Nutrients, 10.","DOI":"10.3390\/nu10020163"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1016\/j.ajog.2006.03.054","article-title":"Placental transfer of rosiglitazone in the ex vivo human perfusion model","volume":"195","author":"Holmes","year":"2006","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.fertnstert.2004.10.045","article-title":"Placental transfer of rosiglitazone in the first trimester of human pregnancy","volume":"83","author":"Chan","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/14767050801929901","article-title":"Effect of albumin on transplacental transfer and distribution of rosiglitazone and glyburide","volume":"21","author":"Nanovskaya","year":"2008","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.fertnstert.2006.03.024","article-title":"An in vivo murine model of rosiglitazone use in pregnancy","volume":"86","author":"Klinkner","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.reprotox.2004.11.003","article-title":"A case of rosiglitazone exposure in the second trimester of pregnancy","volume":"19","author":"Kalyoncu","year":"2005","journal-title":"Reprod. Toxicol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1177\/0960327117730883","article-title":"Effects of prenatal PPAR-\u03b3 agonist rosiglitazone exposure on rat hippocampus development in a time-dependent manner: A stereological and histopathological study","volume":"37","author":"Eren","year":"2018","journal-title":"Human. Exp. Toxicol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.fertnstert.2005.12.069","article-title":"Effect of rosiglitazone on embryonic growth and morphology: A study using a whole rat embryo culture model","volume":"86","author":"Chan","year":"2006","journal-title":"Fertil. Steril."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3625","DOI":"10.1210\/en.2007-0211","article-title":"Ligand-activated peroxisome proliferator activated receptor gamma alters placental morphology and placental fatty acid uptake in mice","volume":"148","author":"Schaiff","year":"2007","journal-title":"Endocrinology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4969","DOI":"10.1210\/en.2010-0131","article-title":"PPARgamma in placental angiogenesis","volume":"151","author":"Nadra","year":"2010","journal-title":"Endocrinology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s12020-009-9229-4","article-title":"Effects of rosiglitazone on ovarian function and fertility in animals with reduced fertility following fetal and neonatal exposure to nicotine","volume":"36","author":"Petrik","year":"2009","journal-title":"Endocrine"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"113928","DOI":"10.18632\/oncotarget.23043","article-title":"Gestational diabetes mellitus is associated with decreased adipose and placenta peroxisome proliferator-activator receptor \u03b3 expression in a Chinese population","volume":"8","author":"Gao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/jdi.12928","article-title":"Downregulation of peroxisome proliferator-activated receptor gamma in the placenta correlates to hyperglycemia in offspring at young adulthood after exposure to gestational diabetes mellitus","volume":"10","author":"Zhao","year":"2019","journal-title":"J. Diabetes Investig."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1515\/jpm-2013-0039","article-title":"Peroxisome proliferator-activated receptor-gamma (PPARgamma) is down regulated in trophoblast cells of gestational diabetes mellitus (GDM) and in trophoblast tumour cells BeWo in vitro after stimulation with PPARgamma agonists","volume":"42","author":"Knabl","year":"2014","journal-title":"J. Perinat. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1113\/JP280593","article-title":"Mitochondrial dysfunction in placental trophoblast cells experiencing gestational diabetes mellitus","volume":"599","author":"Fisher","year":"2021","journal-title":"J. Physiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.placenta.2006.04.002","article-title":"Expression and potential role of peroxisome proliferator-activated receptor gamma in the placenta of diabetic pregnancy","volume":"28","author":"Suwaki","year":"2007","journal-title":"Placenta"},{"key":"ref_119","first-page":"779","article-title":"Gestational diabetes mellitus is associated with increased leukocyte peroxisome proliferator-activated receptor \u03b3 expression","volume":"11","author":"Nadel","year":"2015","journal-title":"Arch. Med. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/aji.12339","article-title":"Glucose and metformin modulate human first trimester trophoblast function: A model and potential therapy for diabetes-associated uteroplacental insufficiency","volume":"73","author":"Han","year":"2015","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/molehr\/gah090","article-title":"Influence of peroxisome proliferator-activated receptor gamma activation by its endogenous ligand 15-deoxy Delta12,14 prostaglandin J2 on nitric oxide production in term placental tissues from diabetic women","volume":"10","author":"Jawerbaum","year":"2004","journal-title":"Mol. Hum. Reprod."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1080\/21655979.2021.2012906","article-title":"C1q\/tumor necrosis factor related protein 6 (CTRP6) regulates the phenotypes of high glucose-induced gestational trophoblast cells via peroxisome proliferator-activated receptor gamma (PPARgamma) signaling","volume":"13","author":"Zhang","year":"2022","journal-title":"Bioengineered"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/FM9.0000000000000044","article-title":"The Activation of Peroxisome Proliferator-activated Receptor \u03b3 Enhances Insulin Signaling Pathways via Up-regulating Chemerin Expression in High Glucose Treated HTR-8\/SVneo Cells","volume":"2","author":"Zhou","year":"2020","journal-title":"Matern.-Fetal Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.mce.2015.04.015","article-title":"Peroxisome proliferator-activated receptor gamma enhances adiponectin secretion via up-regulating DsbA-L expression","volume":"411","author":"Jin","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1631\/jzus.B2000432","article-title":"Silencing of DsbA-L gene impairs the PPARgamma agonist function of improving insulin resistance in a high-glucose cell model","volume":"21","author":"Zhou","year":"2020","journal-title":"J. Zhejiang Univ. Sci. B"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/11\/2459\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:41:42Z","timestamp":1760125302000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/11\/2459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,25]]},"references-count":125,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["nu15112459"],"URL":"https:\/\/doi.org\/10.3390\/nu15112459","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,25]]}}}