{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:28:10Z","timestamp":1790810890952,"version":"4.1.0"},"reference-count":34,"publisher":"MathDoc\/Centre Mersenne","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Pregnancy complications occur frequently and are particularly prevalent during the first trimester. They are caused by a multitude of factors, including karyotypic, genetic or environmental conditions, congenital infections and inflammation. The molecular mechanisms leading to placental complications under inflammatory conditions remain unclear. In this review, we discuss how uncontrolled inflammation, triggered by viral infections or other diseases can lead to placental complications. We first highlight the importance of syncytins, ancestral retroviral genes co-opted by mammals including humans, millions of years ago for the process of placenta formation. We then focus on recent advances elucidating how interferon-induced transmembrane (IFITM) proteins, antiviral proteins rendering cells refractory to viral infections, interfere with placental development.<\/jats:p>","DOI":"10.5802\/crbiol.54","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T04:20:16Z","timestamp":1625199616000},"page":"145-156","source":"Crossref","is-referenced-by-count":8,"title":["Pregnancy complications and Interferon-induced transmembrane proteins (IFITM): balancing antiviral immunity and placental development"],"prefix":"10.5802","volume":"344","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4790-7577","authenticated-orcid":false,"given":"Julian","family":"Buchrieser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0729-1475","authenticated-orcid":false,"given":"Olivier","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3842","published-online":{"date-parts":[[2021,7,2]]},"reference":[{"key":"key2025102316430484091_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aat6114","article-title":"Immune responses at the maternal-fetal interface","volume":"4","author":"Ander, S. E.","year":"2019","unstructured":"[1] Ander, S. E.; Diamond, M. S.; Coyne, C. B. Immune responses at the maternal-fetal interface, Sci. Immunol., Volume 4 (2019), eaat6114","journal-title":"Sci. Immunol."},{"key":"key2025102316430484091_2","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.immuni.2018.07.017","article-title":"Interferons and proinflammatory cytokines in pregnancy and fetal development","volume":"49","author":"Yockey, L. J.","year":"2018","unstructured":"[2] Yockey, L. J.; Iwasaki, A. Interferons and proinflammatory cytokines in pregnancy and fetal development, Immunity, Volume 49 (2018), pp. 397-412","journal-title":"Immunity"},{"key":"key2025102316430484091_3","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aao1680","article-title":"Type I interferons instigate fetal demise after Zika virus infection","volume":"3","author":"Yockey, L. J.","year":"2018","unstructured":"[3] Yockey, L. J.; Jurado, K. A.; Arora, N.; Millet, A.; Rakib, T.; Milano, K. M.; Hastings, A. K.; Fikrig, E. et al. Type I interferons instigate fetal demise after Zika virus infection, Sci. Immunol., Volume 3 (2018), eaao1680","journal-title":"Sci. Immunol."},{"key":"key2025102316430484091_4","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1126\/science.aaw7733","article-title":"IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise","volume":"365","author":"Buchrieser, J.","year":"2019","unstructured":"[4] Buchrieser, J.; Degrelle, S. A.; Couderc, T.; Nevers, Q.; Disson, O.; Manet, C.; Donahue, D. A.; Porrot, F. et al. IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise, Science, Volume 365 (2019), pp. 176-180","journal-title":"Science"},{"key":"key2025102316430484091_5","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.mpaic.2014.01.004","article-title":"Functions of the placenta","volume":"15","author":"Donnelly, L.","year":"2014","unstructured":"[5] Donnelly, L.; Campling, G. Functions of the placenta, Anaesth. Intensive Care Med., Volume 15 (2014), pp. 136-139","journal-title":"Anaesth. Intensive Care Med."},{"key":"key2025102316430484091_6","doi-asserted-by":"publisher","first-page":"3479","DOI":"10.1007\/s00018-019-03104-6","article-title":"Human placenta and trophoblast development: key molecular mechanisms and model systems","volume":"76","author":"Kn\u00f6fler, M.","year":"2019","unstructured":"[6] Kn\u00f6fler, M.; Haider, S.; Saleh, L.; Pollheimer, J.; Gamage, T. K. J. B.; James, J. Human placenta and trophoblast development: key molecular mechanisms and model systems, Cell Mol. Life Sci., Volume 76 (2019), pp. 3479-3496","journal-title":"Cell Mol. Life Sci."},{"key":"key2025102316430484091_7","doi-asserted-by":"publisher","first-page":"4481","DOI":"10.1242\/dev.155523","article-title":"The hallmarks of cell-cell fusion","volume":"144","author":"Hern\u00e1ndez, J. M.","year":"2017","unstructured":"[7] Hern\u00e1ndez, J. M.; Podbilewicz, B. The hallmarks of cell-cell fusion, Development, Volume 144 (2017), pp. 4481-4495","journal-title":"Development"},{"key":"key2025102316430484091_8","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2012.0507","article-title":"Paleovirology of \u2018<span class=\"italique\">syncytins<\/span>\u2019, retroviral <span class=\"italique\">env<\/span> genes exapted for a role in placentation","volume":"368","author":"Lavialle, C.","year":"2013","unstructured":"[8] Lavialle, C.; Cornelis, G.; Dupressoir, A.; Esnault, C.; Heidmann, O.; Vernochet, C.; Heidmann, T. Paleovirology of \u2018syncytins\u2019, retroviral env genes exapted for a role in placentation, Phil. Trans. R. Soc. B, Volume 368 (2013), 20120507","journal-title":"Phil. Trans. R. Soc. B"},{"key":"key2025102316430484091_9","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nrmicro817","article-title":"Virus entry: molecular mechanisms and biomedical applications","volume":"2","author":"Dimitrov, D. S.","year":"2004","unstructured":"[9] Dimitrov, D. S. Virus entry: molecular mechanisms and biomedical applications, Nat. Rev. Microbiol., Volume 2 (2004), pp. 109-122","journal-title":"Nat. Rev. Microbiol."},{"key":"key2025102316430484091_10","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/s41579-019-0189-2","article-title":"Origins and evolutionary consequences of ancient endogenous retroviruses","volume":"17","author":"Johnson, W. E.","year":"2019","unstructured":"[10] Johnson, W. E. Origins and evolutionary consequences of ancient endogenous retroviruses, Nat. Rev. Microbiol., Volume 17 (2019), pp. 355-370","journal-title":"Nat. Rev. Microbiol."},{"key":"key2025102316430484091_11","doi-asserted-by":"publisher","first-page":"4922","DOI":"10.1016\/j.jmb.2019.10.020","article-title":"X-ray structures of the post-fusion 6-Helix bundle of the human syncytins and their functional implications","volume":"431","author":"Ruigrok, K.","year":"2019","unstructured":"[11] Ruigrok, K.; Vaney, M.-C.; Buchrieser, J.; Baquero, E.; Hellert, J.; Baron, B.; England, P.; Schwartz, O.; Rey, F. A.; Backovic, M. X-ray structures of the post-fusion 6-Helix bundle of the human syncytins and their functional implications, J. Mol. Biol., Volume 431 (2019), pp. 4922-4940","journal-title":"J. Mol. Biol."},{"key":"key2025102316430484091_12","doi-asserted-by":"publisher","first-page":"S35","DOI":"10.1016\/j.placenta.2014.12.015","article-title":"Review: An overview of molecular events occurring in human trophoblast fusion","volume":"36","author":"Gerbaud, P.","year":"2015","unstructured":"[12] Gerbaud, P.; Pidoux, G. Review: An overview of molecular events occurring in human trophoblast fusion, Placenta, Volume 36 (2015), p. S35-S42","journal-title":"Placenta"},{"key":"key2025102316430484091_13","doi-asserted-by":"publisher","first-page":"12127","DOI":"10.1073\/pnas.0902925106","article-title":"Syncytin-A knockout mice demonstrate the critical role in placentation of a fusogenic, endogenous retrovirus-derived, envelope gene","volume":"106","author":"Dupressoir, A.","year":"2009","unstructured":"[13] Dupressoir, A.; Vernochet, C.; Bawa, O.; Harper, F.; Pierron, G.; Opolon, P.; Heidmann, T. Syncytin-A knockout mice demonstrate the critical role in placentation of a fusogenic, endogenous retrovirus-derived, envelope gene, Proc. Natl. Acad. Sci. USA, Volume 106 (2009), pp. 12127-12132","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"key2025102316430484091_14","doi-asserted-by":"publisher","first-page":"E1164","DOI":"10.1073\/pnas.1112304108","article-title":"A pair of co-opted retroviral envelope syncytin genes is required for formation of the two-layered murine placental syncytiotrophoblast","volume":"108","author":"Dupressoir, A.","year":"2011","unstructured":"[14] Dupressoir, A.; Vernochet, C.; Harper, F.; Gu\u00e9gan, J.; Dessen, P.; Pierron, G.; Heidmann, T. A pair of co-opted retroviral envelope syncytin genes is required for formation of the two-layered murine placental syncytiotrophoblast, Proc. Natl. Acad. Sci. USA, Volume 108 (2011), p. E1164-E1173","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"key2025102316430484091_15","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms8121965","article-title":"Retroviral restriction factors and their viral targets: restriction strategies and evolutionary adaptations","volume":"8","author":"Boso, G.","year":"2020","unstructured":"[15] Boso, G.; Kozak, C. A. Retroviral restriction factors and their viral targets: restriction strategies and evolutionary adaptations, Microorganisms, Volume 8 (2020), 1965","journal-title":"Microorganisms"},{"key":"key2025102316430484091_16","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.immuni.2012.08.013","article-title":"Intrinsic cellular defenses against human immunodeficiency viruses","volume":"37","author":"Blanco-Melo, D.","year":"2012","unstructured":"[16] Blanco-Melo, D.; Venkatesh, S.; Bieniasz, P. D. Intrinsic cellular defenses against human immunodeficiency viruses, Immunity, Volume 37 (2012), pp. 399-411","journal-title":"Immunity"},{"key":"key2025102316430484091_17","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/nri2314","article-title":"Interferon-inducible antiviral effectors","volume":"8","author":"Sadler, A. J.","year":"2008","unstructured":"[17] Sadler, A. J.; Williams, B. R. G. Interferon-inducible antiviral effectors, Nat. Rev. Immunol., Volume 8 (2008), pp. 559-568","journal-title":"Nat. Rev. Immunol."},{"key":"key2025102316430484091_18","article-title":"More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteins","volume":"14","author":"Shi, G.","year":"2017","unstructured":"[18] Shi, G.; Schwartz, O.; Compton, A. A. More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteins, Retrovirology, Volume 14 (2017), 53","journal-title":"Retrovirology"},{"key":"key2025102316430484091_19","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1016\/j.cell.2009.12.017","article-title":"The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile Virus, and Dengue Virus","volume":"139","author":"Brass, A. L.","year":"2009","unstructured":"[19] Brass, A. L.; Huang, I. C.; Benita, Y.; John, S. P.; Krishnan, M. N.; Feeley, E. M.; Ryan, B. J.; Weyer, J. L. et al. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile Virus, and Dengue Virus, Cell, Volume 139 (2009), pp. 1243-1254","journal-title":"Cell"},{"key":"key2025102316430484091_20","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.chom.2014.11.001","article-title":"IFITM Proteins incorporated into HIV-1 virions impair viral fusion and spread","volume":"16","author":"Compton, A. A.","year":"2014","unstructured":"[20] Compton, A. A.; Bruel, T.; Porrot, F.; Mallet, A.; Sachse, M.; Euvrard, M.; Liang, C.; Casartelli, N.; Schwartz, O. IFITM Proteins incorporated into HIV-1 virions impair viral fusion and spread, Cell Host Microbiol., Volume 16 (2014), pp. 736-747","journal-title":"Cell Host Microbiol."},{"key":"key2025102316430484091_21","doi-asserted-by":"publisher","first-page":"2323","DOI":"10.1016\/j.celrep.2016.05.074","article-title":"The IFITMs inhibit zika virus replication","volume":"15","author":"Savidis, G.","year":"2016","unstructured":"[21] Savidis, G.; Perreira, J. M.; Portmann, J. M.; Meraner, P.; Guo, Z.; Green, S.; Brass, A. L. The IFITMs inhibit zika virus replication, Cell Rep., Volume 15 (2016), pp. 2323-2330","journal-title":"Cell Rep."},{"key":"key2025102316430484091_22","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020106267","article-title":"Syncytia formation by SARS-CoV-2 infected cells","volume":"39","author":"Buchrieser, J.","year":"2020","unstructured":"[22] Buchrieser, J.; Dufloo, J.; Hubert, M.; Monel, B.; Planas, D.; Michael Rajah, M.; Planchais, C.; Porrot, F. et al. Syncytia formation by SARS-CoV-2 infected cells, EMBO J., Volume 39 (2020), e106267","journal-title":"EMBO J."},{"key":"key2025102316430484091_23","article-title":"Opposing activities of IFITM proteins in SARS-CoV-2 infection","volume":"40","author":"Shi, G.","year":"2020","unstructured":"[23] Shi, G.; Kenney, A. D.; Kudryashova, E.; Zani, A.; Zhang, L.; Lai, K. K.; Hall-Stoodley, L; Robinson, R. T. et al. Opposing activities of IFITM proteins in SARS-CoV-2 infection, EMBO J., Volume 40 (2020), e106501","journal-title":"EMBO J."},{"key":"key2025102316430484091_24","doi-asserted-by":"publisher","first-page":"8155","DOI":"10.1021\/acsnano.0c10567","article-title":"Interferon-induced transmembrane protein 3 blocks fusion of diverse enveloped viruses by altering mechanical properties of cell membranes","volume":"15","author":"Guo, X.","year":"2021","unstructured":"[24] Guo, X.; Steink\u00fchler, J.; Marin, M.; Li, X.; Lu, W.; Dimova, R.; Melikyan, G. B. Interferon-induced transmembrane protein 3 blocks fusion of diverse enveloped viruses by altering mechanical properties of cell membranes, ACS Nano., Volume 15 (2021), pp. 8155-8170","journal-title":"ACS Nano."},{"key":"key2025102316430484091_25","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.yexcr.2015.06.015","article-title":"A new cell-based assay to evaluate myogenesis in mouse myoblast C2C12 cells","volume":"336","author":"Kodaka, M.","year":"2015","unstructured":"[25] Kodaka, M.; Yang, Z.; Nakagawa, K.; Maruyama, J.; Xu, X.; Sarkar, A.; Ichimura, A.; Nasu, Y. et al. A new cell-based assay to evaluate myogenesis in mouse myoblast C2C12 cells, Exp. Cell Res., Volume 336 (2015), pp. 171-181","journal-title":"Exp. Cell Res."},{"key":"key2025102316430484091_26","doi-asserted-by":"publisher","first-page":"19844","DOI":"10.1074\/jbc.AC119.010611","article-title":"Interferon-induced transmembrane proteins inhibit cell fusion mediated by trophoblast syncytins","volume":"294","author":"Zani, A.","year":"2019","unstructured":"[26] Zani, A.; Zhang, L.; McMichael, T. M.; Kenney, A. D.; Chemudupati, M.; Kwiek, J. J.; Liu, S.-L.; Yount, J. S. Interferon-induced transmembrane proteins inhibit cell fusion mediated by trophoblast syncytins, J. Biol. Chem., Volume 294 (2019), pp. 19844-19851","journal-title":"J. Biol. Chem."},{"key":"key2025102316430484091_27","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1146\/annurev-cellbio-100814-125620","article-title":"Placenta: the forgotten organ","volume":"31","author":"Maltepe, E.","year":"2015","unstructured":"[27] Maltepe, E.; Fisher, S. J. Placenta: the forgotten organ, Annu. Rev. Cell Dev. Biol., Volume 31 (2015), pp. 523-552","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"key2025102316430484091_28","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1038\/nm.4370","article-title":"SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans","volume":"23","author":"Allen, E. K.","year":"2017","unstructured":"[28] Allen, E. K.; Randolph, A. G.; Bhangale, T.; Dogra, P.; Ohlson, M.; Oshansky, C. M.; Zamora, A. E.; Shannon, J. P. et al. SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans, Nat. Med., Volume 23 (2017), pp. 975-983","journal-title":"Nat. Med."},{"key":"key2025102316430484091_29","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nature10921","article-title":"IFITM3 restricts the morbidity and mortality associated with influenza","volume":"484","author":"Everitt, A. R.","year":"2012","unstructured":"[29] Everitt, A. R.; Clare, S.; Pertel, T.; John, S. P.; Wash, R. S.; Smith, S. E.; Chin, C. R.; Feeley, E. M. et al. IFITM3 restricts the morbidity and mortality associated with influenza, Nature, Volume 484 (2012), pp. 519-523","journal-title":"Nature"},{"key":"key2025102316430484091_30","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1038\/s41586-020-2681-2","article-title":"The innate immunity protein IFITM3 modulates <span class=\"mathjax-formula\" data-tex=\"$\\gamma $\"><math xmlns=\"http:\/\/www.w3.org\/1998\/Math\/MathML\"><mi>\u03b3<\/mi><\/math><\/span>-secretase in Alzheimer\u2019s disease","volume":"586","author":"Hur, J.-Y.","year":"2020","unstructured":"[30] Hur, J.-Y.; Frost, G. R.; Wu, X.; Crump, C.; Pan, S. J.; Wong, E.; Barros, M.; Li, T. et al. The innate immunity protein IFITM3 modulates \u03b3-secretase in Alzheimer\u2019s disease, Nature, Volume 586 (2020), pp. 735-740","journal-title":"Nature"},{"key":"key2025102316430484091_31","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1172\/JCI84889","article-title":"The antiviral restriction factor IFN-induced transmembrane protein 3 prevents cytokine-driven CMV pathogenesis","volume":"127","author":"Stacey, M. A.","year":"2017","unstructured":"[31] Stacey, M. A.; Clare, S.; Clement, M.; Marsden, M.; Abdul-Karim, J.; Kane, L.; Harcourt, K.; Brandt, C. et al. The antiviral restriction factor IFN-induced transmembrane protein 3 prevents cytokine-driven CMV pathogenesis, J. Clin. Invest., Volume 127 (2017), pp. 1463-1474","journal-title":"J. Clin. Invest."},{"key":"key2025102316430484091_32","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1111\/imcb.12000","article-title":"The anti-inflammatory IFITM genes ameliorate colitis and partially protect from tumorigenesis by changing immunity and microbiota","volume":"96","author":"Alteber, Z.","year":"2018","unstructured":"[32] Alteber, Z.; Sharbi-Yunger, A.; Pevsner-Fischer, M.; Blat, D.; Roitman, L.; Tzehoval, E.; Elinav, E.; Eisenbach, L. The anti-inflammatory IFITM genes ameliorate colitis and partially protect from tumorigenesis by changing immunity and microbiota, Immunol. Cell Biol., Volume 96 (2018), pp. 284-297","journal-title":"Immunol. Cell Biol."},{"key":"key2025102316430484091_33","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1002\/2211-5463.12479","article-title":"IFITM3 promotes hepatocellular carcinoma invasion and metastasis by regulating MMP9 through p38\/MAPK signaling","volume":"8","author":"Min, J.","year":"2018","unstructured":"[33] Min, J.; Feng, Q.; Liao, W.; Liang, Y.; Gong, C.; Li, E.; He, W.; Yuan, R.; Wu, L. IFITM3 promotes hepatocellular carcinoma invasion and metastasis by regulating MMP9 through p38\/MAPK signaling, FEBS Open Bio., Volume 8 (2018), pp. 1299-1311","journal-title":"FEBS Open Bio."},{"key":"key2025102316430484091_34","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/s41586-020-2884-6","article-title":"IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells","volume":"588","author":"Lee, J.","year":"2020","unstructured":"[34] Lee, J.; Robinson, M. E.; Ma, N.; Artadji, D.; Ahmed, M. A.; Xiao, G.; Sadras, T. et al. IFITM3 functions as a PIP3 scaffold to amplify PI3K signalling in B cells, Nature, Volume 588 (2020), pp. 491-497","journal-title":"Nature"}],"container-title":["Comptes Rendus. Biologies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/comptes-rendus.academie-sciences.fr\/biologies\/item\/10.5802\/crbiol.54.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T14:59:27Z","timestamp":1761231567000},"score":1,"resource":{"primary":{"URL":"https:\/\/comptes-rendus.academie-sciences.fr\/biologies\/articles\/10.5802\/crbiol.54\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,2]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021]]}},"alternative-id":["10.5802\/crbiol.54"],"URL":"https:\/\/doi.org\/10.5802\/crbiol.54","relation":{},"ISSN":["1631-0691","1768-3238"],"issn-type":[{"value":"1631-0691","type":"print"},{"value":"1768-3238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,2]]}}}