{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T17:47:08Z","timestamp":1772128028833,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T00:00:00Z","timestamp":1586476800000},"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>We reported earlier that an anti-inflammatory small peptide receptor-formyl peptide receptor-2 (FPR2) was significantly decreased in placentas from third trimester pregnancies complicated with fetal growth restriction (FGR), compared to placentas from uncomplicated control pregnancies, suggesting FPR2 may play a role in the development of FGR. The aim of this study is to investigate whether the actions of FPR2 alters placental growth process in humans. Accordingly, using small-for-gestation age (SGA) as a proxy for FGR, we hypothesize that FPR2 expression is decreased in first-trimester placentas of women who later manifest FGR, and contributes to aberrant trophoblast function and the development of FGR. Chorionic villus sampling (CVS) tissues were collected at 10\u201312 weeks gestation in 70 patients with singleton fetuses; surplus tissue was used. Real-time PCR and immunoassays were performed to quantitate FPR2 gene and protein expression. Silencing of FPR2 was performed in two independent, trophoblast-derived cell lines, HTR-8\/SVneo and JEG-3 to investigate the functional consequences of FPR2 gene downregulation. FPR2 mRNA relative to 18S rRNA was significantly decreased in placentae from SGA-pregnancies (n = 28) compared with controls (n = 52) (p &lt; 0.0001). Placental FPR2 protein was significantly decreased in SGA compared with control (n = 10 in each group, p &lt; 0.05). Proliferative, migratory and invasive potential of the human placental-derived cell lines, HTR-8\/SVneo and JEG-3 were significantly reduced in siFPR2 treated cells compared with siCONT control groups. Down-stream signaling molecules, STAT5B and SOCS3 were identified as target genes of FPR2 action in the trophoblast-derived cell lines and in SGA and control chorionic villous tissues. FPR2 is a novel regulator of key molecular pathways and functions in placental development, and its decreased expression in women destined to develop FGR reinforces a placental origin of SGA\/FGR, and that it contributes to causing the development of SGA\/FGR.<\/jats:p>","DOI":"10.3390\/cells9040921","type":"journal-article","created":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T05:31:16Z","timestamp":1586496676000},"page":"921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Decreased Placental FPR2 in Early Pregnancies That Later Developed Small-For-Gestation Age: A Potential Role of FPR2 in the Regulation of Epithelial-Mesenchymal Transition"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2535-5134","authenticated-orcid":false,"given":"Padma","family":"Murthi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria 3052, Australia"},{"name":"Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3168, Australia"},{"name":"Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1914-0137","authenticated-orcid":false,"given":"Gayathri","family":"Rajaraman","sequence":"additional","affiliation":[{"name":"First year college, Victoria University, St Albans, Victoria 3021, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan Jaap H.M.","family":"Erwich","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Groningen, 9700 RB Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evdokia","family":"Dimitriadis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria 3052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.siny.2004.03.006","article-title":"Developmental biology of the placenta and the origins of placental insufficiency","volume":"9","author":"Chaddha","year":"2004","journal-title":"Semin. 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