{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:02:41Z","timestamp":1792789361231,"version":"4.5.0"},"reference-count":68,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,4]],"date-time":"2023-02-04T00:00:00Z","timestamp":1675468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020","award":["765274"],"award-info":[{"award-number":["765274"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Premature ageing of the placenta in pregnancy outcomes is associated with the persistent presence of oxidative stress and placental insufficiency reducing its functional capacity. In this study, we investigated cellular senescence phenotypes of pre-eclampsia and IUGR pregnancies by simultaneously measuring several biomarkers of senescence. Maternal plasma and placental samples were collected at term gestation from nulliparous women undergoing pre-labour elective caesarean section with pre-eclampsia without intrauterine growth restriction (PE; n = 5), pre-eclampsia associated with intrauterine growth restriction (n = 8), intrauterine growth restriction (IUGR &lt; 10th centile; n = 6), and age-matched controls (n = 20). Placental absolute telomere length and senescence gene analysis was performed by RTqPCR. The expression of cyclin-dependent kinase inhibitors (p21 and p16) was determined by Western blot. Senescence-associated secretory phenotypes (SASPs) were evaluated in maternal plasma by multiplex ELISA assay. Placental expression of senescence-associated genes showed significant increases in CHEK1, PCNA, PTEN, CDKN2A, and CCNB-1 (p &lt; 0.05) in pre-eclampsia, while TBX-2, PCNA, ATM, and CCNB-1 expression were evident (p &lt; 0.05) and were significantly decreased in IUGR compared with controls. Placental p16 protein expression was significantly decreased in pre-eclampsia only compared with controls (p = 0.028). IL-6 was significantly increased in pre-eclampsia (0.54 pg\/mL \u00b1 0.271 vs. 0.3 pg\/mL \u00b1 0.102; p = 0.017) while IFN-\u03b3 was significantly increased in IUGR (4.6 pg\/mL \u00b1 2.2 vs. 2.17 pg\/mL \u00b1 0.8; p = 0.002) compared with controls. These results provide evidence of premature senescence in IUGR pregnancies, and while cell cycle checkpoint regulators are activated in pre-eclampsia, the cellular phenotype is one of cell repair and subsequent proliferation rather than progression to senescence. The heterogeneity of these cellular phenotypes highlights the complexity of characterising cellular senescence and may equally be indicative of the differing pathophysiological insults unique to each obstetric complication.<\/jats:p>","DOI":"10.3390\/ijms24043101","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T03:34:30Z","timestamp":1675654470000},"page":"3101","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Heterogenous Differences in Cellular Senescent Phenotypes in Pre-Eclampsia and IUGR following Quantitative Assessment of Multiple Biomarkers of Senescence"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6280-8070","authenticated-orcid":false,"given":"Samprikta","family":"Manna","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, University College Cork, T12 YE02 Cork, Ireland"},{"name":"INFANT Research Centre, University College Cork, T12 K8AF Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5303-6205","authenticated-orcid":false,"given":"Colm J.","family":"Mc Elwain","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Western Gateway Building, University College Cork, T12 XF62 Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6722-0484","authenticated-orcid":false,"given":"Gillian M.","family":"Maher","sequence":"additional","affiliation":[{"name":"INFANT Research Centre, University College Cork, T12 K8AF Cork, Ireland"},{"name":"School of Public Health, Western Gateway Building, University College Cork, T12 XF62 Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Giralt Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Western Gateway Building, University College Cork, T12 XF62 Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2497-0699","authenticated-orcid":false,"given":"Andrea","family":"Musumeci","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Western Gateway Building, University College Cork, T12 XF62 Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fergus P.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, University College Cork, T12 YE02 Cork, Ireland"},{"name":"INFANT Research Centre, University College Cork, T12 K8AF Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9514-9021","authenticated-orcid":false,"given":"Cathal","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Western Gateway Building, University College Cork, T12 XF62 Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.preghy.2018.05.004","article-title":"The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice","volume":"13","author":"Brown","year":"2018","journal-title":"Pregnancy Hypertens."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.3109\/14767058.2016.1152249","article-title":"Intrauterine growth restriction\u2014Part 1","volume":"29","author":"Sharma","year":"2016","journal-title":"J. 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