{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T11:31:17Z","timestamp":1778671877701,"version":"3.51.4"},"reference-count":72,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T00:00:00Z","timestamp":1703808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia","award":["451-03-47\/2023-01\/200019"],"award-info":[{"award-number":["451-03-47\/2023-01\/200019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Successful pregnancy establishment requires highly synchronized cross talk between the invasive trophoblast cells and the receptive maternal endometrium. Any disturbances in this tightly regulated process may lead to pregnancy complications. Local factors such as nutrients, hormones, cytokines and reactive oxygen species modulate the invasion of extravillous trophoblasts through critical signaling cascades. Epidemiological studies strongly indicate that a Mediterranean diet can significantly impact molecular pathways during placentation. Therefore, the aim of the current study was to examine whether oleuropein (OLE), one of the main compounds of the Mediterranean diet, may influence trophoblast cell adhesion and migration, as well as the expression of invasion-associated molecular markers and inflammatory pathways fostering these processes. HTR-8\/SVneo cells were incubated with OLE at selected concentrations of 10 and 100 \u00b5M for 24 h. Results showed that OLE did not affect trophoblast cell viability, proliferation and adhesion after 24 h in in vitro treatment. The mRNA expression of integrin subunits \u03b11, \u03b15 and \u03b21, as well as matrix-degrading enzymes MMP-2 and -9, was significantly increased after treatment with 10 \u00b5M OLE. Furthermore, OLE at a concentration of 10 \u00b5M significantly increased the protein expression of integrin subunits \u03b11 and \u03b21. Also, OLE inhibited the activation of JNK and reduced the protein expression of COX-2. Finally, a lower concentration of OLE 10 \u00b5M significantly stimulated migration of HTR-8\/SVneo cells. In conclusion, the obtained results demonstrate the effects of OLE on the function of trophoblast cells by promoting cell migration and stimulating the expression of invasion markers. As suggested from results, these effects may be mediated via inhibition of the JNK signaling pathway.<\/jats:p>","DOI":"10.3390\/ijms25010500","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T11:19:21Z","timestamp":1703848761000},"page":"500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Oleuropein Stimulates Migration of Human Trophoblast Cells and Expression of Invasion-Associated Markers"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1182-4895","authenticated-orcid":false,"given":"Andrea","family":"Pirkovi\u0107","sequence":"first","affiliation":[{"name":"Institute for the Application of Nuclear Energy, Department for Biology of Reproduction, University of Belgrade, Banatska 31b, 11080 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8292-4853","authenticated-orcid":false,"given":"Milica","family":"Jovanovi\u0107 Krivoku\u0107a","sequence":"additional","affiliation":[{"name":"Institute for the Application of Nuclear Energy, Department for Biology of Reproduction, University of Belgrade, Banatska 31b, 11080 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Viloti\u0107","sequence":"additional","affiliation":[{"name":"Institute for the Application of Nuclear Energy, Department for Biology of Reproduction, University of Belgrade, Banatska 31b, 11080 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0750-9347","authenticated-orcid":false,"given":"Mirjana","family":"Nacka-Aleksi\u0107","sequence":"additional","affiliation":[{"name":"Institute for the Application of Nuclear Energy, Department for Biology of Reproduction, University of Belgrade, Banatska 31b, 11080 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u017danka","family":"Boji\u0107-Trbojevi\u0107","sequence":"additional","affiliation":[{"name":"Institute for the Application of Nuclear Energy, Department for Biology of Reproduction, University of Belgrade, Banatska 31b, 11080 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8467-4165","authenticated-orcid":false,"given":"Dragana","family":"Dekanski","sequence":"additional","affiliation":[{"name":"Institute for the Application of Nuclear Energy, Department for Biology of Reproduction, University of Belgrade, Banatska 31b, 11080 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Huang, C.-C., Hsueh, Y.-W., Chang, C.-W., Hsu, H.-C., Yang, T.-C., Lin, W.-C., and Chang, H.-M. (2023). Establishment of the Fetal-Maternal Interface: Developmental Events in Human Implantation and Placentation. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1200330"},{"key":"ref_2","doi-asserted-by":"crossref","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":"Haider","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lawless, L., Qin, Y., Xie, L., and Zhang, K. (2023). Trophoblast Differentiation: Mechanisms and Implications for Pregnancy Complications. Nutrients, 15.","DOI":"10.3390\/nu15163564"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1118121","DOI":"10.3389\/fendo.2023.1118121","article-title":"Oxidative Stress on Vessels at the Maternal-Fetal Interface for Female Reproductive System Disorders: Update","volume":"14","author":"Zhang","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9962860","DOI":"10.1155\/2021\/9962860","article-title":"The Role of Oxidative Stress and Antioxidant Balance in Pregnancy","volume":"2021","author":"Hussain","year":"2021","journal-title":"Mediators Inflamm."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Nacka-Aleksi\u0107, M., Pirkovi\u0107, A., Viloti\u0107, A., Boji\u0107-Trbojevi\u0107, \u017d., Jovanovi\u0107 Krivoku\u0107a, M., Giampieri, F., Battino, M., and Dekanski, D. (2022). The Role of Dietary Polyphenols in Pregnancy and Pregnancy-Related Disorders. Nutrients, 14.","DOI":"10.3390\/nu14245246"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"101098","DOI":"10.1016\/j.mam.2022.101098","article-title":"The Influence of the Dietary Exposome on Oxidative Stress in Pregnancy Complications","volume":"87","author":"Prins","year":"2022","journal-title":"Mol. Asp. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1093\/humupd\/dmy037","article-title":"The Impact of Periconceptional Maternal Lifestyle on Clinical Features and Biomarkers of Placental Development and Function: A Systematic Review","volume":"25","author":"Reijnders","year":"2019","journal-title":"Hum. Reprod. Update"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"570","DOI":"10.3389\/fendo.2018.00570","article-title":"Regulation of Placental Development and Its Impact on Fetal Growth\u2014New Insights From Mouse Models","volume":"9","author":"Woods","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e466","DOI":"10.1016\/j.fertnstert.2020.08.1342","article-title":"A Preconception lifestyle intervention improves some gestational outcomes and neonatal markers of adiposity in women with obesity and infertility","volume":"114","author":"Rouissi","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e40","DOI":"10.1016\/j.fertnstert.2019.07.234","article-title":"A Lifestyle Intervention Targeting Women with Obesity and Infertility Improves Their Fertility Outcomes, Especially in Women with PCOS: A Randomized Controlled Trial","volume":"112","author":"Belan","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Amati, F., Hassounah, S., and Swaka, A. (2019). The Impact of Mediterranean Dietary Patterns During Pregnancy on Maternal and Offspring Health. Nutrients, 11.","DOI":"10.3390\/nu11051098"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Su\u00e1rez-Mart\u00ednez, C., Yag\u00fce-Guirao, G., Santaella-Pascual, M., Peso-Echarri, P., Vioque, J., Morales, E., Garc\u00eda-Marcos, L., and Mart\u00ednez-Graci\u00e1, C. (2021). Adherence to the Mediterranean Diet and Determinants among Pregnant Women: The NELA Cohort. Nutrients, 13.","DOI":"10.20944\/preprints202103.0482.v1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.23880\/fsnt-16000239","article-title":"Nutriepigenomics: Need of the Day to Integrate Genetics, Epigenetics and Environment towards Nutritious Food for Healthy Life","volume":"5","author":"Suresh","year":"2020","journal-title":"Food Sci. Nutr. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4322","DOI":"10.1210\/jc.2016-1858","article-title":"Effects of Resveratrol on Polycystic Ovary Syndrome: A Double-Blind, Randomized, Placebo-Controlled Trial","volume":"101","author":"Banaszewska","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3389\/fcvm.2018.00188","article-title":"Vasculoprotective Role of Olive Oil Compounds via Modulation of Oxidative Stress in Atherosclerosis","volume":"5","author":"Summerhill","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Pojero, F., Aiello, A., Gervasi, F., Caruso, C., Ligotti, M.E., Calabr\u00f2, A., Procopio, A., Candore, G., Accardi, G., and Allegra, M. (2022). Effects of Oleuropein and Hydroxytyrosol on Inflammatory Mediators: Consequences on Inflammaging. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010380"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10408398.2022.2160960","article-title":"Common Pregnancy Complications and Polyphenols Intake: An Overview","volume":"3","author":"Deckmann","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1002\/ptr.6511","article-title":"Oleuropein: A Natural Antioxidant Molecule in the Treatment of Metabolic Syndrome","volume":"33","author":"Ahamad","year":"2019","journal-title":"Phyther. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"17409","DOI":"10.18632\/oncotarget.15538","article-title":"Oleuropein, Unexpected Benefits!","volume":"8","author":"Sun","year":"2017","journal-title":"Oncotarget"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Romero-M\u00e1rquez, J.M., Forbes-Hern\u00e1ndez, T.Y., Navarro-Hortal, M.D., Quirantes-Pin\u00e9, R., Grosso, G., Giampieri, F., Lipari, V., S\u00e1nchez-Gonz\u00e1lez, C., Battino, M., and Quiles, J.L. (2023). Molecular Mechanisms of the Protective Effects of Olive Leaf Polyphenols against Alzheimer\u2019s Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054353"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"18508","DOI":"10.3390\/ijms151018508","article-title":"Effects of the Olive-Derived Polyphenol Oleuropein on Human Health","volume":"15","author":"Barbaro","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Park, Y., Cho, Y.J., Sung, N., Park, M.J., Guan, X., Gibbons, W.E., O\u2019Malley, B.W., and Han, S.J. (2022). Oleuropein Suppresses Endometriosis Progression and Improves the Fertility of Mice with Endometriosis. J. Biomed. Sci., 29.","DOI":"10.1186\/s12929-022-00883-2"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1530\/EC-20-0466","article-title":"Oleuropein Alleviates Gestational Diabetes Mellitus by Activating AMPK Signaling","volume":"10","author":"Zhang","year":"2021","journal-title":"Endocr. Connect."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pirkovi\u0107, A., Viloti\u0107, A., Borozan, S., Nacka-Aleksi\u0107, M., Boji\u0107-Trbojevi\u0107, \u017d., Krivoku\u0107a, M.J., Battino, M., Giampieri, F., and Dekanski, D. (2023). Oleuropein Attenuates Oxidative Stress in Human Trophoblast Cells. Antioxidants, 12.","DOI":"10.3390\/antiox12010197"},{"key":"ref_26","first-page":"12016","article-title":"Pro-Inflammatory Mediators and Signaling Proteins in the Decidua of Pre-Eclampsia","volume":"24","author":"Jung","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ozmen, A., Guzeloglu-Kayisli, O., Tabak, S., Guo, X., Semerci, N., Nwabuobi, C., Larsen, K., Wells, A., Uyar, A., and Arlier, S. (2022). Preeclampsia Is Associated With Reduced ISG15 Levels Impairing Extravillous Trophoblast Invasion. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.898088"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.placenta.2018.06.313","article-title":"TGF-\u03921 Inhibits Human Trophoblast Cell Invasion by Upregulating Cyclooxygenase-2","volume":"68","author":"Yi","year":"2018","journal-title":"Placenta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s00418-016-1474-z","article-title":"The Trophoblast Plug during Early Pregnancy: A Deeper Insight","volume":"146","author":"Weiss","year":"2016","journal-title":"Histochem. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.theriogenology.2020.02.002","article-title":"Matrix Metalloproteinases Improves Trophoblast Invasion and Pregnancy Potential in Mice","volume":"151","author":"Zhang","year":"2020","journal-title":"Theriogenology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1053\/plac.2000.0521","article-title":"Paracrine and Autocrine Regulators of Trophoblast Invasion\u2014A Review","volume":"21","author":"Bischoff","year":"2000","journal-title":"Placenta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1080\/jmf.13.1.39.44","article-title":"Maternal Serum of Women with Pre-Eclampsia Reduces Trophoblast Cell Viability: Evidence for an Increased Sensitivity to Fas-Mediated Apoptosis","volume":"13","author":"Neale","year":"2003","journal-title":"J. Matern. Neonatal Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Jena, M.K., Sharma, N.R., Petitt, M., Maulik, D., and Nayak, N.R. (2020). Pathogenesis of Preeclampsia and Therapeutic Approaches Targeting the Placenta. Biomolecules, 10.","DOI":"10.3390\/biom10060953"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.102.014977","article-title":"Endovascular Trophoblast Invasion: Implications for the Pathogenesis of Intrauterine Growth Retardation and Preeclampsia","volume":"69","author":"Kaufmann","year":"2003","journal-title":"Biol. Reprod."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"18415","DOI":"10.1038\/s41598-021-97799-y","article-title":"Oxidative Stress-Induced Impairment of Trophoblast Function Causes Preeclampsia through the Unfolded Protein Response Pathway","volume":"11","author":"Mukherjee","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1093\/humrep\/dex069","article-title":"Enhancement of Trophoblast Differentiation and Survival by Low Molecular Weight Heparin Requires Heparin-Binding EGF-like Growth Factor","volume":"32","author":"Bolnick","year":"2017","journal-title":"Hum. Reprod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"20570","DOI":"10.3390\/molecules191220570","article-title":"Resveratrol Inhibits Trophoblast Apoptosis through Oxidative Stress in Preeclampsia-Model Rats","volume":"19","author":"Zou","year":"2014","journal-title":"Molecules"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1007\/s12011-016-0870-5","article-title":"Overexpression of Endogenous Anti-Oxidants with Selenium Supplementation Protects Trophoblast Cells from Reactive Oxygen Species-Induced Apoptosis in a Bcl-2-Dependent Manner","volume":"177","author":"Khera","year":"2017","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.placenta.2008.04.009","article-title":"Vitamins C and E Inhibit Apoptosis of Cultured Human Term Placenta Trophoblast","volume":"29","author":"Tannetta","year":"2008","journal-title":"Placenta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.placenta.2023.11.008","article-title":"Aspirin Protects Human Trophoblast HTR-8\/SVneo Cells from H2O2-Induced Oxidative Stress via NADPH\/ROS Pathway","volume":"144","author":"Guo","year":"2023","journal-title":"Placenta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/19336918.2022.2055520","article-title":"Unravelling Cell Migration: Defining Movement from the Cell Surface","volume":"16","year":"2022","journal-title":"Cell Adh. Migr."},{"key":"ref_42","first-page":"e58942","article-title":"In Vitro Assays to Evaluate the Migration, Invasion, and Proliferation of Immortalized Human First-Trimester Trophoblast Cell Lines","volume":"145","author":"Kisanga","year":"2019","journal-title":"J. Vis. Exp."},{"key":"ref_43","first-page":"1934578X1601100","article-title":"Antiproliferative Properties of Oleuropein in Human Osteosarcoma Cells","volume":"11","author":"Moran","year":"2016","journal-title":"Nat. Prod. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bossio, S., Perri, A., Malivindi, R., Giordano, F., Rago, V., Mirabelli, M., Salatino, A., Brunetti, A., Greco, E.A., and Aversa, A. (2022). Oleuropein Counteracts Both the Proliferation and Migration of Intra- and Extragonadal Seminoma Cells. Nutrients, 14.","DOI":"10.3390\/nu14112323"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.3892\/or.2016.4978","article-title":"Oleuropein Inhibits the Proliferation and Invasion of Glioma Cells via Suppression of the AKT Signaling Pathway","volume":"36","author":"Liu","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Soundararajan, R., and Rao, A.J. (2004). Trophoblast \u201cPseudo-Tumorigenesis\u201d: Significance and Contributory Factors. Reprod. Biol. Endocrinol., 2.","DOI":"10.1186\/1477-7827-2-15"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1093\/humupd\/dml048","article-title":"Molecular Circuits Shared by Placental and Cancer Cells, and Their Implications in the Proliferative, Invasive and Migratory Capacities of Trophoblasts","volume":"13","author":"Ferretti","year":"2006","journal-title":"Hum. Reprod. Update"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"31747","DOI":"10.1039\/D2RA02593K","article-title":"Inhibitory Effect of Phenolic Extract from Squirting Cucumber (Ecballium elaterium (L.) A. Rich) Seed Oil on Integrin-Mediated Cell Adhesion, Migration and Angiogenesis","volume":"12","author":"Morjen","year":"2022","journal-title":"RSC Adv."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.bcp.2019.04.023","article-title":"The Effects of Flavonoids on Human First Trimester Trophoblast Spheroidal Stem Cell Self-Renewal, Invasion and JNK\/P38 MAPK Activation: Understanding the Cytoprotective Effects of These Phytonutrients against Oxidative Stress","volume":"164","author":"Ebegboni","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"22983","DOI":"10.1074\/jbc.M603040200","article-title":"Redox Regulation of \u03b2-Actin during Integrin-Mediated Cell Adhesion","volume":"281","author":"Fiaschi","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1158\/1541-7786.MCR-07-0197","article-title":"Salvicine Inactivates \u03921 Integrin and Inhibits Adhesion of MDA-MB-435 Cells to Fibronectin via Reactive Oxygen Species Signaling","volume":"6","author":"Zhou","year":"2008","journal-title":"Mol. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Mukherjee, I., Biswas, S., Singh, S., Talukdar, J., Alqahtani, M.S., Abbas, M., Nag, T.C., Mridha, A.R., Gupta, S., and Sharma, J.B. (2023). Monosodium Glutamate Perturbs Human Trophoblast Invasion and Differentiation through a Reactive Oxygen Species-Mediated Pathway: An In-Vitro Assessment. Antioxidants, 12.","DOI":"10.3390\/antiox12030634"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.bbamcr.2006.12.009","article-title":"The C-Jun Kinase\/Stress-Activated Pathway: Regulation, Function and Role in Human Disease","volume":"1773","author":"Johnson","year":"2007","journal-title":"Biochim. Biophys. Acta\u2014Mol. Cell Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1128\/IAI.06295-11","article-title":"Reactive Oxygen Species-Triggered Trophoblast Apoptosis Is Initiated by Endoplasmic Reticulum Stress via Activation of Caspase-12, CHOP, and the JNK Pathway in Toxoplasma Gondii Infection in Mice","volume":"80","author":"Xu","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.2353\/ajpath.2007.061035","article-title":"Nuclear Factor-\u039aB, P38, and Stress-Activated Protein Kinase Mitogen-Activated Protein Kinase Signaling Pathways Regulate Proinflammatory Cytokines and Apoptosis in Human Placental Explants in Response to Oxidative Stress","volume":"170","author":"Jauniaux","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ba\u010denkov\u00e1, D., Trebu\u0148ov\u00e1, M., \u010c\u00ed\u017ekov\u00e1, D., Hud\u00e1k, R., Dosedla, E., Findrik-Balogov\u00e1, A., and \u017div\u010d\u00e1k, J. (2022). In Vitro Model of Human Trophoblast in Early Placentation. Biomedicines, 10.","DOI":"10.3390\/biomedicines10040904"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1177\/1933719110361960","article-title":"Neutrophil Expression of Cyclooxygenase 2 in Preeclampsia","volume":"17","author":"Bachawaty","year":"2010","journal-title":"Reprod. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1093\/biolre\/ioz186","article-title":"Regulation of Placentation by the Transforming Growth Factor Beta Superfamily\u2020","volume":"102","author":"Ding","year":"2020","journal-title":"Biol. Reprod."},{"key":"ref_59","first-page":"19","article-title":"Olive Oil Polyphenols Suppress the TGF-\u03b1-induced Migration of Hepatocellular Carcinoma Cells","volume":"11","author":"Yamada","year":"2019","journal-title":"Biomed. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"105880","DOI":"10.1016\/j.jff.2023.105880","article-title":"Oleuropein and Its Hydrolysate from Extra Virgin Olive Oil Inhibit Breast Cancer Cells Proliferation Interfering with the PI3K-AKT Signal Pathway","volume":"110","author":"Han","year":"2023","journal-title":"J. Funct. Foods"},{"key":"ref_61","unstructured":"Erdo\u011fan, \u0130., Bayraktar, O., Uslu, M.E., and Tuncel, \u00d6. (2018). Wound Healing Effects of Various Fractions of Olive Leaf Extract (OLE) on Mouse Fibroblasts. Rom. Biotechnol. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Utami, N.D., Nordin, A., Katas, H., Bt Hj Idrus, R., and Fauzi, M.B. (2020). Molecular Action of Hydroxytyrosol in Wound Healing: An In Vitro Evidence-Based Review. Biomolecules, 10.","DOI":"10.3390\/biom10101397"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1002\/ptr.5339","article-title":"Role of Hydroxytyrosol-dependent Regulation of HO-1 Expression in Promoting Wound Healing of Vascular Endothelial Cells via Nrf2 de novo Synthesis and Stabilization","volume":"29","author":"Zrelli","year":"2015","journal-title":"Phyther. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8826","DOI":"10.3892\/mmr.2017.7701","article-title":"Hydroxytyrosol Contributes to Cell Proliferation and Inhibits Apoptosis in Pulsed Electromagnetic Fields Treated Human Umbilical Vein Endothelial Cells in vitro","volume":"16","author":"Cheng","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/jn\/135.3.525","article-title":"Low Concentrations of Flavonoids Are Protective in Rat H4IIE Cells Whereas High Concentrations Cause DNA Damage and Apoptosis","volume":"135","author":"Michels","year":"2005","journal-title":"J. Nutr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"173","DOI":"10.2478\/v10102-011-0027-5","article-title":"Toxicological Aspects of the Use of Phenolic Compounds in Disease Prevention","volume":"4","author":"Kyselova","year":"2011","journal-title":"Interdiscip. Toxicol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Scicchitano, S., Vecchio, E., Battaglia, A.M., Oliverio, M., Nardi, M., Procopio, A., Costanzo, F., Biamonte, F., and Faniello, M.C. (2023). The Double-Edged Sword of Oleuropein in Ovarian Cancer Cells: From Antioxidant Functions to Cytotoxic Effects. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010842"},{"key":"ref_68","first-page":"64","article-title":"Cytoprotective and Genoprotective Effects of Taxifolin against Oxidative Damage in HTR-8\/SVneo Human Trophoblast Cells","volume":"38","year":"2022","journal-title":"Mutagenesis"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"103364","DOI":"10.1016\/j.jri.2021.103364","article-title":"Decidual IDO+ Macrophage Promotes the Proliferation and Restricts the Apoptosis of Trophoblasts","volume":"148","author":"Huang","year":"2021","journal-title":"J. Reprod. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1083\/jcb.200309105","article-title":"Latent TGF-\u03b2 Binding Protein LTBP-2 Decreases Fibroblast Adhesion to Fibronectin","volume":"163","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e92221","DOI":"10.1590\/fst.92221","article-title":"Quercetin Inhibits the Expression of MiRNA-155 and Improves the Functions of Lipopolysaccharide-Induced Human Extravillous","volume":"42","author":"Liu","year":"2022","journal-title":"Food Sci. Technol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.placenta.2009.01.013","article-title":"Interleukin-6 Stimulates Cell Migration, Invasion and Integrin Expression in HTR-8\/SVneo Cell Line","volume":"30","year":"2009","journal-title":"Placenta"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/500\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:44:31Z","timestamp":1760132671000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/1\/500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,29]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25010500"],"URL":"https:\/\/doi.org\/10.3390\/ijms25010500","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,29]]}}}