{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:25:52Z","timestamp":1791350752816,"version":"4.3.1"},"reference-count":50,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human embryonic implantation involves major invasion of the uterine wall and remodeling of the uterine arteries by extravillous cytotrophoblast cells (EVCT). Abnormalities in these early steps of placental development lead to poor placentation and fetal growth defects and are frequently associated with preeclampsia, a major complication of human pregnancy. We recently showed that oxidized low-density lipoproteins (oxLDLs) are present in situ in EVCT and inhibit cell invasion in a concentration-dependent manner. The aim of the present study was to better understand the mechanisms by which oxLDL modulate trophoblast invasion. We therefore investigated the presence of oxLDL receptors in our cell culture model of human invasive primary EVCT. We found using immunocytochemistry and immunoblotting that the lectin-like oxLDL receptor-1 was the scavenger receptor mainly expressed in EVCT and was probably involved in oxLDL uptake. We next examined the effect of low-density lipoprotein oxidative state on trophoblast invasion in vitro using EVCT cultured on Matrigel-coated Transwell. We demonstrated that only oxLDL containing a high proportion of oxysterols and phosphatidylcholine hydroperoxide derivatives that provide ligands for liver X receptor (LXR) and peroxisomal proliferator-activated receptor \u03b3 (PPAR\u03b3), respectively, reduced trophoblast invasion. We next investigated the presence and the role of these nuclear receptors and found that in addition to PPAR\u03b3, human invasive trophoblasts express LXR\u03b2, and activation of these nuclear receptors by specific synthetic or natural ligands inhibited trophoblast invasion. Finally, using a PPAR\u03b3 antagonist, we suggest that LXR\u03b2, rather than PPAR\u03b3, is involved in oxLDL-mediated inhibition of human trophoblast invasion in vitro.<\/jats:p>","DOI":"10.1210\/en.2003-1747","type":"journal-article","created":{"date-parts":[[2004,7,9]],"date-time":"2004-07-09T00:34:50Z","timestamp":1089333290000},"page":"4583-4591","source":"Crossref","is-referenced-by-count":76,"title":["Lipids from Oxidized Low-Density Lipoprotein Modulate Human Trophoblast Invasion: Involvement of Nuclear Liver X Receptors"],"prefix":"10.1210","volume":"145","author":[{"given":"Lae\u0308titia","family":"Pavan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axelle","family":"Hermouet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilis","family":"Tsatsaris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"The\u0301rond","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Sawamura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danie\u0300le","family":"Evain-Brion","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Fournier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612434789500_R1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1242\/jcs.99.4.681","article-title":"Implantation, trophoblast differentiation and haemochorial placentation: mechanistic evidence in vivo and in vitro.","volume":"99","author":"Aplin","year":"1991","journal-title":"J Cell Sci"},{"key":"2020071612434789500_R2","first-page":"32","author":"Loke","year":"1995"},{"key":"2020071612434789500_R3","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1006\/scel.1993.1022","article-title":"Human cytotrophoblast invasion.","volume":"4","author":"Fisher","year":"1993","journal-title":"Semin Cell Biol"},{"key":"2020071612434789500_R4","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/nm0697-610","article-title":"Cytotrophoblasts: masters of disguise.","volume":"3","author":"Redman","year":"1997","journal-title":"Nat Med"},{"key":"2020071612434789500_R5","author":"Redman","year":"1993"},{"key":"2020071612434789500_R6","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1046\/j.1525-1373.1999.d01-139.x","article-title":"Oxidative stress in the pathogenesis of preeclampsia.","volume":"222","author":"Hubel","year":"1999","journal-title":"Proc Soc Exp Biol Med"},{"key":"2020071612434789500_R7","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0029-7844(96)00514-5","article-title":"Lipoprotein subfraction concentrations in preeclampsia: pathogenic parallels to atherosclerosis.","volume":"89","author":"Sattar","year":"1997","journal-title":"Obstet Gynecol"},{"key":"2020071612434789500_R8","first-page":"2483","article-title":"Lipoprotein subfraction changes in normal pregnancy: threshold effect of plasma triglyceride on appearance of small, dense low density lipoprotein.","volume":"82","author":"Sattar","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612434789500_R9","doi-asserted-by":"crossref","first-page":"4543","DOI":"10.1210\/jcem.85.12.7027","article-title":"Low density lipoprotein (LDL) subfractions during pregnancy: accumulation of buoyant LDL with advancing gestation.","volume":"85","author":"Winkler","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612434789500_R10","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/0021-9150(96)05842-X","article-title":"Influence of plasma lipid and LDL-subfraction profile on the interaction between low density lipoprotein with human arterial wall proteoglycans.","volume":"124","author":"Anber","year":"1996","journal-title":"Atherosclerosis"},{"key":"2020071612434789500_R11","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S0890-6238(99)00033-7","article-title":"Levels of lipid peroxides in uncomplicated pregnancy: a review of the literature.","volume":"13","author":"Little","year":"1999","journal-title":"Reprod Toxicol"},{"key":"2020071612434789500_R12","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1016\/0002-9378(93)90419-J","article-title":"Secretion of lipid peroxides by the human placenta.","volume":"169","author":"Walsh","year":"1993","journal-title":"Am J Obstet Gynecol"},{"key":"2020071612434789500_R13","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0021-9150(94)05404-7","article-title":"Metabolism of modified LDL by cultured human placental cells.","volume":"112","author":"Bonet","year":"1995","journal-title":"Atherosclerosis"},{"key":"2020071612434789500_R14","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1210\/jc.2003-032042","article-title":"Oxidized low-density lipoproteins inhibit trophoblastic cell invasion.","volume":"89","author":"Pavan","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612434789500_R15","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1038\/labinvest.3780334","article-title":"Characterization of human villous and extravillous trophoblasts isolated from first trimester placenta.","volume":"81","author":"Tarrade","year":"2001","journal-title":"Lab Invest"},{"key":"2020071612434789500_R16","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":"2020071612434789500_R17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0014-5793(99)00564-5","article-title":"Major differences in oxysterol formation in human low density lipoproteins (LDLs) oxidized by *OH\/O2*- free radicals or by copper.","volume":"451","author":"Zarev","year":"1999","journal-title":"FEBS Lett"},{"key":"2020071612434789500_R18","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1161\/01.ATV.19.3.810","article-title":"Cholesteryl ester hydroperoxide lability is a key feature of the oxidative susceptibility of small, dense LDL.","volume":"19","author":"Chancharme","year":"1999","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2020071612434789500_R19","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/0003-2697(87)90606-3","article-title":"Detection and characterization of lipid hydroperoxides at picomole levels by high-performance liquid chromatography.","volume":"160","author":"Yamamoto","year":"1987","journal-title":"Anal Biochem"},{"key":"2020071612434789500_R20","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/BF02522885","article-title":"Hydroperoxides of erythrocyte phospholipid molecular species formed by lipoxygenase correlate with \u03b1-tocopherol levels.","volume":"31","author":"Therond","year":"1996","journal-title":"Lipids"},{"key":"2020071612434789500_R21","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/S0022-2275(20)37619-7","article-title":"Free and esterified oxysterol: formation during copper-oxidation of low density lipoprotein and uptake by macrophages.","volume":"37","author":"Brown","year":"1996","journal-title":"J Lipid Res"},{"key":"2020071612434789500_R22","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1021\/bi00789a030","article-title":"Electrophoretic analysis of the major polypeptides of the human erythrocyte membrane.","volume":"10","author":"Fairbanks","year":"1971","journal-title":"Biochemistry"},{"key":"2020071612434789500_R23","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/386073a0","article-title":"An endothelial receptor for oxidized low-density lipoprotein.","volume":"386","author":"Sawamura","year":"1997","journal-title":"Nature"},{"key":"2020071612434789500_R24","doi-asserted-by":"crossref","first-page":"31217","DOI":"10.1074\/jbc.272.50.31217","article-title":"Expression cloning of a novel scavenger receptor from human endothelial cells.","volume":"272","author":"Adachi","year":"1997","journal-title":"J Biol Chem"},{"key":"2020071612434789500_R25","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1006\/bbrc.2001.5044","article-title":"Induction of the oxLDL receptor LOX-1 by endothelin-1 in human endothelial cells.","volume":"284","author":"Morawietz","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071612434789500_R26","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.abb.2003.09.022","article-title":"Extent of copper LDL oxidation depends on oxidation time and copper\/LDL ratio: chemical characterization.","volume":"420","author":"Zarev","year":"2003","journal-title":"Arch Biochem Biophys"},{"key":"2020071612434789500_R27","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0022-2275(20)37617-3","article-title":"Longitudinal study on lipoprotein profile, high density lipoprotein subclass, and postheparin lipases during gestation in women.","volume":"37","author":"Alvarez","year":"1996","journal-title":"J Lipid Res"},{"key":"2020071612434789500_R28","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/0891-5849(95)02173-6","article-title":"The role of oxidized lipoproteins in atherogenesis.","volume":"20","author":"Berliner","year":"1996","journal-title":"Free Radic Biol Med"},{"key":"2020071612434789500_R29","doi-asserted-by":"crossref","first-page":"561","DOI":"10.3109\/07853899109150518","article-title":"Macrophages and oxidized low density lipoproteins in the pathogenesis of atherosclerosis.","volume":"23","author":"Yla-Herttuala","year":"1991","journal-title":"Ann Med"},{"key":"2020071612434789500_R30","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1095\/biolreprod.101.001925","article-title":"Effect of Matrigel on human extravillous trophoblasts differentiation: modulation of protease pattern gene expression.","volume":"67","author":"Tarrade","year":"2002","journal-title":"Biol Reprod"},{"key":"2020071612434789500_R31","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1242\/jcs.114.7.1273","article-title":"Characterization of residues and sequences of the carbohydrate recognition domain required for cell surface localization and ligand binding of human lectin-like oxidized LDL receptor.","volume":"114","author":"Shi","year":"2001","journal-title":"J Cell Sci"},{"key":"2020071612434789500_R32","doi-asserted-by":"crossref","first-page":"6573","DOI":"10.1074\/jbc.275.9.6573","article-title":"Biosynthesis and post-translational processing of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1). N-Linked glycosylation affects cell-surface expression and ligand binding.","volume":"275","author":"Kataoka","year":"2000","journal-title":"J Biol Chem"},{"key":"2020071612434789500_R33","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1161\/01.ATV.18.10.1541","article-title":"Ligand specificity of LOX-1, a novel endothelial receptor for oxidized low density lipoprotein.","volume":"18","author":"Moriwaki","year":"1998","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2020071612434789500_R34","doi-asserted-by":"crossref","first-page":"39696","DOI":"10.1074\/jbc.M206140200","article-title":"SREC-II, a new member of the scavenger receptor type F family, trans-interacts with SREC-I through its extracellular domain.","volume":"277","author":"Ishii","year":"2002","journal-title":"J Biol Chem"},{"key":"2020071612434789500_R35","doi-asserted-by":"crossref","first-page":"44222","DOI":"10.1074\/jbc.M103942200","article-title":"The membrane-type collectin CL-P1 is a scavenger receptor on vascular endothelial cells.","volume":"276","author":"Ohtani","year":"2001","journal-title":"J Biol Chem"},{"key":"2020071612434789500_R36","doi-asserted-by":"crossref","first-page":"33068","DOI":"10.1074\/jbc.272.52.33068","article-title":"Structure and localization of the human gene encoding SR-BI\/CLA-1. Evidence for transcriptional control by steroidogenic factor 1.","volume":"272","author":"Cao","year":"1997","journal-title":"J Biol Chem"},{"key":"2020071612434789500_R37","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0143-4004(05)80180-8","article-title":"Acetylated low density lipoprotein endocytosis by human syncytiotrophoblast in culture.","volume":"11","author":"Malassine","year":"1990","journal-title":"Placenta"},{"key":"2020071612434789500_R38","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1161\/01.HYP.37.4.1184","article-title":"8-Iso-prostaglandin F2\u03b1 increases expression of LOX-1 in JAR cells.","volume":"37","author":"Halvorsen","year":"2001","journal-title":"Hypertension"},{"key":"2020071612434789500_R39","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0092-8674(00)81574-3","article-title":"Oxidized LDL regulates macrophage gene expression through ligand activation of PPAR\u03b3.","volume":"93","author":"Nagy","year":"1998","journal-title":"Cell"},{"key":"2020071612434789500_R40","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1161\/01.ATV.20.4.1116","article-title":"Upregulation of endothelial receptor for oxidized LDL (LOX-1) by oxidized LDL and implications in apoptosis of human coronary artery endothelial cells: evidence from use of antisense LOX-1 mRNA and chemical inhibitors.","volume":"20","author":"Li","year":"2000","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2020071612434789500_R41","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1083\/jcb.120.4.1011","article-title":"Oxidized low density lipoprotein inhibits the migration of aortic endothelial cells in vitro.","volume":"120","author":"Murugesan","year":"1993","journal-title":"J Cell Biol"},{"key":"2020071612434789500_R42","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1073\/pnas.85.8.2805","article-title":"Lysophosphatidylcholine: a chemotactic factor for human monocytes and its potential role in atherogenesis.","volume":"85","author":"Quinn","year":"1988","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612434789500_R43","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0092-8674(00)81575-5","article-title":"PPAR\u03b3 promotes monocyte\/macrophage differentiation and uptake of oxidized LDL.","volume":"93","author":"Tontonoz","year":"1998","journal-title":"Cell"},{"key":"2020071612434789500_R44","first-page":"649","article-title":"Peroxisome proliferator-activated receptors: nuclear control of metabolism.","volume":"20","author":"Desvergne","year":"1999","journal-title":"Endocr Rev"},{"key":"2020071612434789500_R45","first-page":"1105","article-title":"The activity of PPAR\u03b3 in primary human trophoblasts is enhanced by oxidized lipids.","volume":"87","author":"Schild","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612434789500_R46","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S1537-1891(02)00175-1","article-title":"LXRs; oxysterol-activated nuclear receptors that regulate genes controlling lipid homeostasis.","volume":"38","author":"Edwards","year":"2002","journal-title":"Vasc Pharmacol"},{"key":"2020071612434789500_R47","doi-asserted-by":"crossref","first-page":"109","DOI":"10.5551\/jat.9.109","article-title":"Effect of deposited lipids in atheromatous lesions on the migration of vascular smooth muscle cells.","volume":"9","author":"Oyama","year":"2002","journal-title":"J Atheroscler Thromb"},{"key":"2020071612434789500_R48","doi-asserted-by":"crossref","first-page":"10443","DOI":"10.1074\/jbc.M213071200","article-title":"Liver X receptor-dependent repression of matrix metalloproteinase-9 expression in macrophages.","volume":"278","author":"Castrillo","year":"2003","journal-title":"J Biol Chem"},{"key":"2020071612434789500_R49","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/0002-9378(89)90778-3","article-title":"Lipid peroxidation in pregnancy: new perspectives on preeclampsia.","volume":"161","author":"Hubel","year":"1989","journal-title":"Am J Obstet Gynecol"},{"key":"2020071612434789500_R50","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S0140-6736(94)92639-5","article-title":"Pre-eclampsia and serum antibodies to oxidised low-density lipoprotein.","volume":"343","author":"Branch","year":"1994","journal-title":"Lancet"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/145\/10\/4583\/9019923\/endo4583.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/145\/10\/4583\/9019923\/endo4583.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T03:30:46Z","timestamp":1624505446000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/145\/10\/4583\/2499807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,10,1]]},"references-count":50,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2004,10,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2003-1747","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,10,1]]}}}