{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:54:14Z","timestamp":1789037654973,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T00:00:00Z","timestamp":1650499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Fetal growth restriction (FGR) is commonly associated with placental insufficiency and inflammation. Nonetheless, the role played by inflammasomes in the pathogenesis of FGR is poorly understood. We hypothesised that placental inflammasomes are differentially expressed and contribute to the aberrant trophoblast function. Inflammasome gene expression profiles were characterised by real-time PCR on human placental tissues collected from third trimester FGR and gestation-matched control pregnancies (n = 25\/group). The functional significance of a candidate inflammasome was then investigated using lipopolysaccharide (LPS)-induced models of inflammation in human trophoblast organoids, BeWo cells in vitro, and a murine model of FGR in vivo. Placental mRNA expression of NLRP3, caspases 1, 3, and 8, and interleukin 6 increased (&gt;2-fold), while that of the anti-inflammatory cytokine, IL-10, decreased (&lt;2-fold) in FGR compared with control pregnancies. LPS treatment increased NLRP3 and caspase-1 expression (&gt;2-fold) in trophoblast organoids and BeWo cell cultures in vitro, and in the spongiotrophoblast and labyrinth in the murine model of FGR. However, the LPS-induced rise in NLRP3 was attenuated by its siRNA-induced down-regulation in BeWo cell cultures, which correlated with reduced activity of the apoptotic markers, caspase-3 and 8, compared to the control siRNA-treated cells. Our findings support the role of the NLRP3 inflammasome in the inflammation-induced aberrant trophoblast function, which may contribute to FGR.<\/jats:p>","DOI":"10.3390\/cells11091413","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T05:07:22Z","timestamp":1650604042000},"page":"1413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["The Placental NLRP3 Inflammasome and Its Downstream Targets, Caspase-1 and Interleukin-6, Are Increased in Human Fetal Growth Restriction: Implications for Aberrant Inflammation-Induced Trophoblast Dysfunction"],"prefix":"10.3390","volume":"11","author":[{"given":"Irvan","family":"Alfian","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia"},{"name":"Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya 6, Jakarta Pusat 10160, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2917-6486","authenticated-orcid":false,"given":"Amlan","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8814-752X","authenticated-orcid":false,"given":"Hannah E. J.","family":"Yong","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore 117609, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheetal","family":"Saini","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2340-2366","authenticated-orcid":false,"given":"Ricky W. K.","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bill","family":"Kalionis","sequence":"additional","affiliation":[{"name":"Department of Maternal-Fetal Medicine Pregnancy Research Centre, The Royal Women\u2019s Hospital, Melbourne, VIC 3052, Australia"},{"name":"Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evdokia","family":"Dimitriadis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, VIC 3052, Australia"},{"name":"Gynaecology Research Centre, The Royal Women\u2019s Hospital, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0718-2447","authenticated-orcid":false,"given":"Nadia","family":"Alfaidy","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1292, Biologie et Biotechnologie pour la Sant\u00e9, 38043 Grenoble, France"},{"name":"Commissariat \u00e0 l\u2019Energie Atomique et aux Energies Alternatives (CEA), Biosciences and Biotechnology Institute of Grenoble, 38054 Grenoble, France"},{"name":"Service Obst\u00e9trique & Gyn\u00e9cologie, Centre Hospitalo-Universitaire Grenoble Alpes, University Grenoble-Alpes, CEDEX 9, 38043 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon D.","family":"Ricardo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0295-4214","authenticated-orcid":false,"given":"Chrishan S.","family":"Samuel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2535-5134","authenticated-orcid":false,"given":"Padma","family":"Murthi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia"},{"name":"Department of Maternal-Fetal Medicine Pregnancy Research Centre, The Royal Women\u2019s Hospital, Melbourne, VIC 3052, Australia"},{"name":"Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jpeds.2017.12.059","article-title":"Consensus Based Definition of Growth Restriction in the Newborn","volume":"196","author":"Beune","year":"2018","journal-title":"J. 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