{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:26:40Z","timestamp":1792168000145,"version":"4.4.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>From the earliest stages of gestation, embryonic\u2013maternal interaction has a key role in a successful pregnancy. Various factors present during gestation may significantly influence this type of juxta\/paracrine interaction. PreImplantation Factor (PIF) is a recently identified factor with activity at the fetomaternal interface. PIF is secreted by viable embryos and directly controls placental development by increasing the invasive capacity of human extravillous trophoblasts (EVTs). To further specify PIF\u2019s role in the human placenta, we analyzed the genome-wide expression profile of the EVT in the presence of a synthetic PIF analog (sPIF). We found that sPIF exposure altered several pathways related to p53 signaling, survival and the immune response. Functional assays revealed that sPIF acts through the p53 pathway to reduce both early and late trophoblast apoptosis. More precisely, sPIF (i) decreases the phosphorylation of p53 at Ser-15, (ii) enhances the B-cell lymphoma-2 (BCL2) expression and (iii) reduces the BCL2-associated X protein (BAX) and BCL2 homologous antagonist killer (BAK) mRNA expression levels. Furthermore, invalidation experiments of TP53 allowed us to demonstrate that PIF\u2019s effects on placental apoptosis seemed to be essentially mediated by this gene. We have clearly shown that p53 and sPIF pathways could interact in human trophoblast and thus promotes cell survival. Furthermore, sPIF was found to regulate a gene network related to immune tolerance in the EVT, which emphasizes the beneficial effect of this peptide on the human placenta. Finally, the PIF protein levels in placentas from pregnancies affected by preeclampsia or intra-uterine growth restriction were significantly lower than in gestational age-matched control placentas. Taken as a whole, our results suggest that sPIF protects the EVT\u2019s functional status through a variety of mechanisms. Clinical application of sPIF in the treatment of disorders of early pregnancy can be envisioned.<\/jats:p>","DOI":"10.1038\/cddis.2016.382","type":"journal-article","created":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T13:47:52Z","timestamp":1480600072000},"page":"e2504-e2504","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Preimplantation factor is an anti-apoptotic effector in human trophoblasts involving p53 signaling pathway"],"prefix":"10.1038","volume":"7","author":[{"given":"Hadia","family":"Moindjie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther Dos","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita-Josiane","family":"Gouesse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Swierkowski-Blanchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Serazin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eytan R","family":"Barnea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Vialard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-No\u00eblle","family":"Dieudonn\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,1]]},"reference":[{"key":"BFcddis2016382_CR1","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S1297-9589(01)00175-8","volume":"29","author":"D Evain-Brion","year":"2001","unstructured":"Evain-Brion D . The 2 differentiation pathways of the human trophoblast. Gyn\u00e9cologie Obst\u00e9trique Fertil 2001; 29: 497\u2013502.","journal-title":"Gyn\u00e9cologie Obst\u00e9trique Fertil"},{"key":"BFcddis2016382_CR2","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/1477-7827-3-56","volume":"3","author":"E Staun-Ram","year":"2005","unstructured":"Staun-Ram E, Shalev E . Human trophoblast function during the implantation process. Reprod Biol Endocrinol 2005; 3: 56.","journal-title":"Reprod Biol Endocrinol"},{"key":"BFcddis2016382_CR3","doi-asserted-by":"publisher","first-page":"S26","DOI":"10.1016\/j.placenta.2007.11.008","volume":"29","author":"M Knofler","year":"2008","unstructured":"Knofler M, Simmons DG, Lash GE, Harris LK, Armant DR . Regulation of trophoblast invasion - a workshop report. Placenta 2008; 29: S26\u2013S28.","journal-title":"Placenta"},{"key":"BFcddis2016382_CR4","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1477-7827-5-6","volume":"5","author":"L Lunghi","year":"2007","unstructured":"Lunghi L, Ferretti ME, Medici S, Biondi C, Vesce F . Control of human trophoblast function. Reprod Biol Endocrinol 2007; 5: 6.","journal-title":"Reprod Biol Endocrinol"},{"key":"BFcddis2016382_CR5","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/1477-7827-9-63","volume":"9","author":"CW Stamatkin","year":"2011","unstructured":"Stamatkin CW, Roussev RG, Stout M, Absalon-Medina V, Ramu S, Goodman C et al. Preimplantation factor (PIF) correlates with early mammalian embryo development-bovine and murine models. Reprod Biol Endocrinol 2011; 9: 63.","journal-title":"Reprod Biol Endocrinol"},{"key":"BFcddis2016382_CR6","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1093\/molehr\/2.11.883","volume":"2","author":"RG Roussev","year":"1996","unstructured":"Roussev RG, Coulam CB, Kaider BD, Yarkoni M, Leavis PC, Barnea ER . Embryonic origin of preimplantation factor (PIF): biological activity and partial characterization. Mol Hum Reprod 1996; 2: 883\u2013887.","journal-title":"Mol Hum Reprod"},{"key":"BFcddis2016382_CR7","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/1866-1955-6-36","volume":"6","author":"CM Duzyj","year":"2014","unstructured":"Duzyj CM, Paidas MJ, Jebailey L, Huang JS, Barnea ER . Preimplantation factor (PIF*) promotes embryotrophic and neuroprotective decidual genes: effect negated by epidermal growth factor. J Neurodev Disord 2014; 6: 36.","journal-title":"J Neurodev Disord"},{"key":"BFcddis2016382_CR8","doi-asserted-by":"publisher","first-page":"e100263","DOI":"10.1371\/journal.pone.0100263","volume":"9","author":"ER Barnea","year":"2014","unstructured":"Barnea ER, Lubman DM, Liu Y-H, Absalon-Medina V, Hayrabedyan S, Todorova K et al. Insight into preimplantation factor (PIF*) mechanism for embryo protection and development: target oxidative stress and protein misfolding (PDI and HSP) through essential RIPK binding site. PloS One 2014; 9: e100263.","journal-title":"PloS One"},{"key":"BFcddis2016382_CR9","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.rbmo.2011.06.009","volume":"23","author":"CW Stamatkin","year":"2011","unstructured":"Stamatkin CW, Roussev RG, Stout M, Coulam CB, Triche E, Godke RA et al. Preimplantation factor negates embryo toxicity and promotes embryo development in culture. Reprod Biomed Online 2011; 23: 517\u2013524.","journal-title":"Reprod Biomed Online"},{"key":"BFcddis2016382_CR10","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/1477-7827-11-105","volume":"11","author":"S Ramu","year":"2013","unstructured":"Ramu S, Stamatkin C, Timms L, Ruble M, Roussev RG, Barnea ER . PreImplantation factor (PIF) detection in maternal circulation in early pregnancy correlates with live birth (bovine model). Reprod Biol Endocrinol 2013; 11: 105.","journal-title":"Reprod Biol Endocrinol"},{"key":"BFcddis2016382_CR11","doi-asserted-by":"publisher","first-page":"459.e1","DOI":"10.1016\/j.ajog.2010.03.024","volume":"202","author":"MJ Paidas","year":"2010","unstructured":"Paidas MJ, Krikun G, Huang SJ, Jones R, Romano M, Annunziato J et al. A genomic and proteomic investigation of the impact of preimplantation factor on human decidual cells. Am J Obstet Gynecol 2010; 202: 459.e1\u2013e8.","journal-title":"Am J Obstet Gynecol"},{"key":"BFcddis2016382_CR12","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/1477-7827-10-50","volume":"10","author":"ER Barnea","year":"2012","unstructured":"Barnea ER, Kirk D, Paidas MJ . PreImplantation factor (PIF) promoting role in embryo implantation: increases endometrial Integrin-\u03b12\u03b23, amphiregulin and epiregulin while reducing betacellulin expression via MAPK in decidua. Reprod Biol Endocrinol 2012; 10: 50.","journal-title":"Reprod Biol Endocrinol"},{"key":"BFcddis2016382_CR13","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1196\/annals.1423.064","volume":"1110","author":"ER Barnea","year":"2007","unstructured":"Barnea ER . Applying embryo-derived immune tolerance to the treatment of immune disorders. Ann N Y Acad Sci 2007; 1110: 602\u2013618.","journal-title":"Ann N Y Acad Sci"},{"key":"BFcddis2016382_CR14","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.jri.2015.06.002","volume":"114","author":"ER Barnea","year":"2016","unstructured":"Barnea ER, Vialard F, Moindjie H, Ornaghi S, Dieudonne MN, Paidas MJ . Preimplantation factor (PIF*) endogenously prevents preeclampsia: promotes trophoblast invasion and reduces oxidative stress. J Reprod Immunol 2016; 114: 58\u201364.","journal-title":"J Reprod Immunol"},{"key":"BFcddis2016382_CR15","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s12020-011-9438-5","volume":"40","author":"L Weiss","year":"2011","unstructured":"Weiss L, Bernstein S, Jones R, Amunugama R, Krizman D, Jebailey L et al. Preimplantation factor (PIF) analog prevents type I diabetes mellitus (TIDM) development by preserving pancreatic function in NOD mice. Endocrine 2011; 40: 41\u201354.","journal-title":"Endocrine"},{"key":"BFcddis2016382_CR16","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.jns.2011.07.050","volume":"312","author":"L Weiss","year":"2012","unstructured":"Weiss L, Or R, Jones RC, Amunugama R, JeBailey L, Ramu S et al. Preimplantation factor (PIF*) reverses neuroinflammation while promoting neural repair in EAE model. J Neurol Sci 2012; 312: 146\u2013157.","journal-title":"J Neurol Sci"},{"key":"BFcddis2016382_CR17","first-page":"456","volume":"68","author":"MJ Paidas","year":"2012","unstructured":"Paidas MJ, Annunziato J, Romano M, Weiss L, Or R, Barnea ER . Pregnancy and multiple sclerosis (MS): a beneficial association. Possible therapeutic application of embryo-specific pre-implantation factor (PIF*). Am J Reprod Immunol N Y N 1989 2012; 68: 456\u2013464.","journal-title":"Am J Reprod Immunol N Y N 1989"},{"key":"BFcddis2016382_CR18","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.bbmt.2012.12.011","volume":"19","author":"Y Azar","year":"2013","unstructured":"Azar Y, Shainer R, Almogi-Hazan O, Bringer R, Compton SR, Paidas MJ et al. Preimplantation factor reduces graft-versus-host disease by regulating immune response and lowering oxidative stress (murine model). Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 2013; 19: 519\u2013528.","journal-title":"Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant"},{"key":"BFcddis2016382_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/718031","volume":"2013","author":"R Shainer","year":"2013","unstructured":"Shainer R, Azar Y, Almogi-Hazan O, Bringer R, Compton SR, Paidas MJ et al. Immune regulation and oxidative stress reduction by preimplantation factor following syngeneic or allogeneic bone marrow transplantation. Conf Pap Med 2013; 2013: 1\u20138.","journal-title":"Conf Pap Med"},{"key":"BFcddis2016382_CR20","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1095\/biolreprod.114.119156","volume":"91","author":"H Moindjie","year":"2014","unstructured":"Moindjie H, Santos ED, Loeuillet L, Gronier H, de Mazancourt P, Barnea ER et al. Preimplantation factor (PIF) promotes human trophoblast invasion. Biol Reprod 2014; 91: 118.","journal-title":"Biol Reprod"},{"key":"BFcddis2016382_CR21","doi-asserted-by":"publisher","first-page":"402.e1","DOI":"10.1016\/j.ajog.2010.06.060","volume":"203","author":"CM Duzyj","year":"2010","unstructured":"Duzyj CM, Barnea ER, Li M, Huang SJ, Krikun G, Paidas MJ . Preimplantation factor promotes first trimester trophoblast invasion. Am J Obstet Gynecol 2010; 203: 402.e1\u2013e4.","journal-title":"Am J Obstet Gynecol"},{"key":"BFcddis2016382_CR22","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.placenta.2012.01.017","volume":"33","author":"MS Longtine","year":"2012","unstructured":"Longtine MS, Chen B, Odibo AO, Zhong Y, Nelson DM . Villous trophoblast apoptosis is elevated and restricted to cytotrophoblasts in pregnancies complicated by preeclampsia, IUGR, or preeclampsia with IUGR. Placenta 2012; 33: 352\u2013359.","journal-title":"Placenta"},{"key":"BFcddis2016382_CR23","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ajog.2005.07.039","volume":"195","author":"B Huppertz","year":"2006","unstructured":"Huppertz B, Kadyrov M, Kingdom JCP . Apoptosis and its role in the trophoblast. Am J Obstet Gynecol 2006; 195: 29\u201339.","journal-title":"Am J Obstet Gynecol"},{"key":"BFcddis2016382_CR24","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1210\/er.2005-0003","volume":"26","author":"SL Straszewski-Chavez","year":"2005","unstructured":"Straszewski-Chavez SL, Abrahams VM, Mor G . The role of apoptosis in the regulation of trophoblast survival and differentiation during pregnancy. Endocr Rev 2005; 26: 877\u2013897.","journal-title":"Endocr Rev"},{"key":"BFcddis2016382_CR25","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1002\/(SICI)1096-9896(199901)187:1<112::AID-PATH250>3.0.CO;2-3","volume":"187","author":"C Prives","year":"1999","unstructured":"Prives C, Hall PA . The p53 pathway. J Pathol 1999; 187: 112\u2013126.","journal-title":"J Pathol"},{"key":"BFcddis2016382_CR26","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/nrc3711","volume":"14","author":"KT Bieging","year":"2014","unstructured":"Bieging KT, Mello SS, Attardi LD . Unravelling mechanisms of p53-mediated tumour suppression. Nat Rev Cancer 2014; 14: 359\u2013370.","journal-title":"Nat Rev Cancer"},{"key":"BFcddis2016382_CR27","doi-asserted-by":"publisher","first-page":"7666","DOI":"10.1093\/nar\/gku501","volume":"42","author":"J Loughery","year":"2014","unstructured":"Loughery J, Cox M, Smith LM, Meek DW . Critical role for p53-serine 15 phosphorylation in stimulating transactivation at p53-responsive promoters. Nucleic Acids Res 2014; 42: 7666\u20137680.","journal-title":"Nucleic Acids Res"},{"key":"BFcddis2016382_CR28","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1080\/01926230701320337","volume":"35","author":"S Elmore","year":"2007","unstructured":"Elmore S . Apoptosis: a review of programmed cell death. Toxicol Pathol 2007; 35: 495\u2013516.","journal-title":"Toxicol Pathol"},{"key":"BFcddis2016382_CR29","doi-asserted-by":"publisher","first-page":"e87621","DOI":"10.1371\/journal.pone.0087621","volume":"9","author":"AN Sharp","year":"2014","unstructured":"Sharp AN, Heazell AEP, Baczyk D, Dunk CE, Lacey HA, Jones CJP et al. Preeclampsia is associated with alterations in the p53-pathway in villous trophoblast. PloS One 2014; 9: e87621.","journal-title":"PloS One"},{"key":"BFcddis2016382_CR30","first-page":"159","volume":"64","author":"AN Sharp","year":"2010","unstructured":"Sharp AN, Heazell AEP, Crocker IP, Mor G . Placental apoptosis in health and disease. Am J Reprod Immunol N Y N 1989 2010; 64: 159\u2013169.","journal-title":"Am J Reprod Immunol N Y N 1989"},{"key":"BFcddis2016382_CR31","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/s10495-010-0551-3","volume":"16","author":"AEP Heazell","year":"2011","unstructured":"Heazell AEP, Sharp AN, Baker PN, Crocker IP . Intra-uterine growth restriction is associated with increased apoptosis and altered expression of proteins in the p53 pathway in villous trophoblast. Apoptosis Int J Program Cell Death 2011; 16: 135\u2013144.","journal-title":"Apoptosis Int J Program Cell Death"},{"key":"BFcddis2016382_CR32","doi-asserted-by":"publisher","first-page":"3453","DOI":"10.1113\/jphysiol.2009.173252","volume":"587","author":"CM Scifres","year":"2009","unstructured":"Scifres CM, Nelson DM . Intrauterine growth restriction, human placental development and trophoblast cell death. J Physiol 2009; 587: 3453\u20133458.","journal-title":"J Physiol"},{"key":"BFcddis2016382_CR33","doi-asserted-by":"publisher","first-page":"970276","DOI":"10.1155\/2013\/970276","volume":"2013","author":"S Hutter","year":"2013","unstructured":"Hutter S, Knabl J, Andergassen U, Jeschke U . The role of PPARs in placental immunology: a systematic review of the literature. PPAR Res 2013; 2013: 970276.","journal-title":"PPAR Res"},{"key":"BFcddis2016382_CR34","doi-asserted-by":"publisher","first-page":"210241","DOI":"10.1155\/2014\/210241","volume":"2014","author":"A Mart\u00ednez-Varea","year":"2014","unstructured":"Mart\u00ednez-Varea A, Pellicer B, Perales-Mar\u00edn A, Pellicer A . Relationship between maternal immunological response during pregnancy and onset of preeclampsia. J Immunol Res 2014; 2014: 210241.","journal-title":"J Immunol Res"},{"key":"BFcddis2016382_CR35","doi-asserted-by":"publisher","first-page":"7839","DOI":"10.1038\/sj.onc.1208932","volume":"24","author":"S Bouleau","year":"2005","unstructured":"Bouleau S, Grimal H, Rincheval V, Godefroy N, Mignotte B, Vayssi\u00e8re J-L et al. FGF1 inhibits p53-dependent apoptosis and cell cycle arrest via an intracrine pathway. Oncogene 2005; 24: 7839\u20137849.","journal-title":"Oncogene"},{"key":"BFcddis2016382_CR36","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/S0092-8674(00)80416-X","volume":"91","author":"SY Shieh","year":"1997","unstructured":"Shieh SY, Ikeda M, Taya Y, Prives C . DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 1997; 91: 325\u2013334.","journal-title":"Cell"},{"key":"BFcddis2016382_CR37","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1128\/MCB.19.3.1751","volume":"19","author":"M Ashcroft","year":"1999","unstructured":"Ashcroft M, Kubbutat MHG, Vousden KH . Regulation of p53 function and stability by phosphorylation. Mol Cell Biol 1999; 19: 1751\u20131758.","journal-title":"Mol Cell Biol"},{"key":"BFcddis2016382_CR38","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1038\/cdd.2015.55","volume":"22","author":"M Mueller","year":"2015","unstructured":"Mueller M, Schoeberlein A, Zhou J, Joerger-Messerli M, Oppliger B, Reinhart U et al. PreImplantation factor bolsters neuroprotection via modulating protein kinase A and protein kinase C signaling. Cell Death Differ 2015; 22: 2078\u20132086.","journal-title":"Cell Death Differ"},{"key":"BFcddis2016382_CR39","doi-asserted-by":"publisher","first-page":"13882","DOI":"10.1073\/pnas.1411674111","volume":"111","author":"M Mueller","year":"2014","unstructured":"Mueller M, Zhou J, Yang L, Gao Y, Wu F, Schoeberlein A et al. PreImplantation factor promotes neuroprotection by targeting microRNA let-7. Proc Natl Acad Sci USA 2014; 111: 13882\u201313887.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis2016382_CR40","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/nn.3113","volume":"15","author":"SM Lehmann","year":"2012","unstructured":"Lehmann SM, Kr\u00fcger C, Park B, Derkow K, Rosenberger K, Baumgart J et al. An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration. Nat Neurosci 2012; 15: 827\u2013835.","journal-title":"Nat Neurosci"},{"key":"BFcddis2016382_CR41","doi-asserted-by":"publisher","first-page":"e32662","DOI":"10.1371\/journal.pone.0032662","volume":"7","author":"A Selvamani","year":"2012","unstructured":"Selvamani A, Sathyan P, Miranda RC, Sohrabji F . An antagomir to microRNA Let7f promotes neuroprotection in an ischemic stroke model. PloS One 2012; 7: e32662.","journal-title":"PloS One"},{"key":"BFcddis2016382_CR42","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1093\/humrep\/det462","volume":"29","author":"AWY Cheong","year":"2014","unstructured":"Cheong AWY, Pang RTK, Liu W-M, Kottawatta KSA, Lee K-F, Yeung WSB . MicroRNA Let-7a and dicer are important in the activation and implantation of delayed implanting mouse embryos. Hum Reprod Oxf Engl 2014; 29: 750\u2013762.","journal-title":"Hum Reprod Oxf Engl"},{"key":"BFcddis2016382_CR43","doi-asserted-by":"publisher","first-page":"e37039","DOI":"10.1371\/journal.pone.0037039","volume":"7","author":"W-M Liu","year":"2012","unstructured":"Liu W-M, Pang RTK, Cheong AWY, Ng EHY, Lao K, Lee K-F et al. Involvement of microRNA lethal-7a in the regulation of embryo implantation in mice. PloS One 2012; 7: e37039.","journal-title":"PloS One"},{"key":"BFcddis2016382_CR44","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1093\/hmg\/ddi048","volume":"14","author":"GS Banting","year":"2005","unstructured":"Banting GS, Barak O, Ames TM, Burnham AC, Kardel MD, Cooch NS et al. CECR2, a protein involved in neurulation, forms a novel chromatin remodeling complex with SNF2L. Hum Mol Genet 2005; 14: 513\u2013524.","journal-title":"Hum Mol Genet"},{"key":"BFcddis2016382_CR45","first-page":"291","volume":"55","author":"S Pongcharoen","year":"2006","unstructured":"Pongcharoen S, Niumsup P, Sanguansermsri D, Supalap K, Butkhamchot P . The effect of interleukin-17 on the proliferation and invasion of JEG-3 human choriocarcinoma cells. Am J Reprod Immunol N Y N 1989 2006; 55: 291\u2013300.","journal-title":"Am J Reprod Immunol N Y N 1989"},{"key":"BFcddis2016382_CR46","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1016\/j.imbio.2015.01.010","volume":"220","author":"ER Barnea","year":"2015","unstructured":"Barnea ER, Kirk D, Todorova K, McElhinney J, Hayrabedyan S, Fern\u00e1ndez N PIF . direct immune regulation: Blocks mitogen-activated PBMCs proliferation, promotes TH2\/TH1 bias, independent of Ca(2+). Immunobiology 2015; 220: 865\u2013875.","journal-title":"Immunobiology"},{"key":"BFcddis2016382_CR47","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.rbmo.2012.09.017","volume":"26","author":"RG Roussev","year":"2013","unstructured":"Roussev RG, Dons\u2019koi BV, Stamatkin C, Ramu S, Chernyshov VP, Coulam CB et al. Preimplantation factor inhibits circulating natural killer cell cytotoxicity and reduces CD69 expression: implications for recurrent pregnancy loss therapy. Reprod Biomed Online 2013; 26: 79\u201387.","journal-title":"Reprod Biomed Online"},{"key":"BFcddis2016382_CR48","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.placenta.2004.12.006","volume":"27","author":"S Itakura","year":"2006","unstructured":"Itakura S, Ohno K, Ueki T, Sato K, Kanayama N . Expression of golf in the rat placenta: possible implication in olfactory receptor transduction. Placenta 2006; 27: 103\u2013108.","journal-title":"Placenta"},{"key":"BFcddis2016382_CR49","first-page":"12718","volume":"8","author":"H Chen","year":"2015","unstructured":"Chen H, Meng T, Liu X, Sun M, Tong C, Liu J et al. Long non-coding RNA MALAT-1 is downregulated in preeclampsia and regulates proliferation, apoptosis, migration and invasion of JEG-3 trophoblast cells. Int J Clin Exp Pathol 2015; 8: 12718\u201312727.","journal-title":"Int J Clin Exp Pathol"},{"key":"BFcddis2016382_CR50","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1053\/j.semperi.2009.02.010","volume":"33","author":"L Duley","year":"2009","unstructured":"Duley L . The global impact of pre-eclampsia and eclampsia. Semin Perinatol 2009; 33: 130\u2013137.","journal-title":"Semin Perinatol"},{"key":"BFcddis2016382_CR51","doi-asserted-by":"publisher","first-page":"239","DOI":"10.3109\/01443615.2012.753423","volume":"33","author":"C O\u2019Connor","year":"2013","unstructured":"O\u2019Connor C, Stuart B, Fitzpatrick C, Turner MJ, Kennelly MM . A review of contemporary modalities for identifying abnormal fetal growth. J Obstet Gynaecol J Inst Obstet Gynaecol 2013; 33: 239\u2013245.","journal-title":"J Obstet Gynaecol J Inst Obstet Gynaecol"},{"key":"BFcddis2016382_CR52","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.placenta.2006.01.019","volume":"28","author":"K Handschuh","year":"2007","unstructured":"Handschuh K, Guibourdenche J, Tsatsaris V, Guesnon M, Laurendeau I, Evain-Brion D et al. Human chorionic gonadotropin expression in human trophoblasts from early placenta: comparative study between villous and extravillous trophoblastic cells. Placenta 2007; 28: 175\u2013184.","journal-title":"Placenta"},{"key":"BFcddis2016382_CR53","first-page":"111","volume":"224","author":"GK Smyth","year":"2003","unstructured":"Smyth GK, Yang YH, Speed T . Statistical issues in cDNA microarray data analysis. Methods Mol Biol Clifton NJ 2003; 224: 111\u2013136.","journal-title":"Methods Mol Biol Clifton NJ"},{"issue":"Database","key":"BFcddis2016382_CR54","doi-asserted-by":"publisher","first-page":"D561","DOI":"10.1093\/nar\/gkq973","volume":"39","author":"D. Szklarczyk","year":"2010","unstructured":"Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P et al. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 2011 39: D561\u2013D568.","journal-title":"Nucleic Acids Research"},{"key":"BFcddis2016382_CR55","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 2005; 102: 15545\u201315550.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFcddis2016382_CR56","doi-asserted-by":"publisher","first-page":"D457","DOI":"10.1093\/nar\/gkv1070","volume":"44","author":"M Kanehisa","year":"2016","unstructured":"Kanehisa M, Sato Y, Kawashima M, Furumichi M, Tanabe M . KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res 2016; 44: D457\u2013D462.","journal-title":"Nucleic Acids Res"},{"key":"BFcddis2016382_CR57","doi-asserted-by":"publisher","first-page":"D355","DOI":"10.1093\/nar\/gkp896","volume":"38","author":"M Kanehisa","year":"2010","unstructured":"Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa M . KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res 2010; 38: D355\u2013D360.","journal-title":"Nucleic Acids Res"},{"key":"BFcddis2016382_CR58","doi-asserted-by":"publisher","first-page":"C853","DOI":"10.1152\/ajpcell.00331.2001","volume":"282","author":"F Machinal-Qu\u00e9lin","year":"2002","unstructured":"Machinal-Qu\u00e9lin F, Dieudonn\u00e9 MN, Leneveu MC, Pecquery R, Giudicelli Y . Proadipogenic effect of leptin on rat preadipocytes in vitro: activation of MAPK and STAT3 signaling pathways. Am J Physiol Cell Physiol 2002; 282: C853\u2013C863.","journal-title":"Am J Physiol Cell Physiol"},{"key":"BFcddis2016382_CR59","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1095\/biolreprod.108.070573","volume":"80","author":"D Benaitreau","year":"2009","unstructured":"Benaitreau D, Dieudonn\u00e9 M-N, Dos Santos E, Leneveu M-C, de Mazancourt P, Pecquery R . Antiproliferative effects of adiponectin on human trophoblastic cell lines JEG-3 and BeWo. Biol Reprod 2009; 80: 1107\u20131114.","journal-title":"Biol Reprod"},{"key":"BFcddis2016382_CR60","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.2144\/97226bm01","volume":"22","author":"SW Perry","year":"1997","unstructured":"Perry SW, Epstein LG, Gelbard HA . In situ Trypan blue staining of monolayer cell cultures for permanent fixation and mounting. BioTechniques 1997; 22: 1020\u20131021 1024.","journal-title":"BioTechniques"},{"key":"BFcddis2016382_CR61","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/S0142-9612(02)00445-3","volume":"24","author":"D Fischer","year":"2003","unstructured":"Fischer D, Li Y, Ahlemeyer B, Krieglstein J, Kissel T . In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials 2003; 24: 1121\u20131131.","journal-title":"Biomaterials"},{"key":"BFcddis2016382_CR62","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/S0006-291X(88)81121-5","volume":"153","author":"D Lacasa","year":"1988","unstructured":"Lacasa D, Agli B, Giudicelli Y . Permissive action of glucocorticoids on catecholamine-induced lipolysis: direct \u2018in vitro\u2019 effects on the fat cell beta-adrenoreceptor-coupled-adenylate cyclase system. Biochem Biophys Res Commun 1988; 153: 489\u2013497.","journal-title":"Biochem Biophys Res Commun"},{"key":"BFcddis2016382_CR63","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","volume":"72","author":"MM Bradford","year":"1976","unstructured":"Bradford MM . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248\u2013254.","journal-title":"Anal Biochem"},{"key":"BFcddis2016382_CR64","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1071\/RD10315","volume":"23","author":"GJ Prakash","year":"2011","unstructured":"Prakash GJ, Suman P, Morales Prieto DM, Markert UR, Gupta SK . Leukaemia inhibitory factor mediated proliferation of HTR-8\/SVneo trophoblast cells is dependent on activation of extracellular signal-regulated kinase 1\/2. Reprod Fertil Dev 2011; 23: 714\u2013724.","journal-title":"Reprod Fertil Dev"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/cddis2016382.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2016382","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/cddis2016382.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T09:10:25Z","timestamp":1672823425000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/cddis2016382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,1]]},"references-count":64,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2016,12]]}},"alternative-id":["BFcddis2016382"],"URL":"https:\/\/doi.org\/10.1038\/cddis.2016.382","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,1]]},"assertion":[{"value":"25 March 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2016","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 October 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2016","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}