{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T18:50:01Z","timestamp":1778611801536,"version":"3.51.4"},"reference-count":92,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,9]],"date-time":"2024-06-09T00:00:00Z","timestamp":1717891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["1R15HL152257"],"award-info":[{"award-number":["1R15HL152257"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Exposure to cigarette smoke is known to induce disease during pregnancy. Recent evidence showed that exposure to secondhand smoke (SHS) negatively impacts fetal and placental weights, leading to the development of intrauterine growth restriction (IUGR). Electronic cigarettes (eCigs) represent a phenomenon that has recently emerged, and their use is also steadily rising. Even so, the effects of SHS or eCigs during gestation remain limited. In the present study, we wanted to characterize the effects of SHS or eCig exposure at two different important gestational points during mouse pregnancy. C57\/Bl6 mice were exposed to SHS or eCigs via a nose-only delivery system for 4 days (from 14.5 to 17.5 gestational days (dGA) or for 6 days (from 12.5 dGA to 17.5 dGA)). At the time of necropsy (18.5 dGA), placental and fetal weights were recorded, maternal blood pressure was determined, and a dipstick test to measure proteinuria was performed. Placental tissues were collected, and inflammatory molecules in the placenta were identified. Treatment with SHS showed the following: (1) a significant decrease in placental and fetal weights following four days of exposure, (2) higher systolic and diastolic blood pressure following six days of exposure, and (3) increased proteinuria after six days of exposure. Treatment with eCigs showed the following: (1) a significant decrease in placental weight and fetal weight following four or six days of exposure, (2) higher systolic and diastolic blood pressure following six days of exposure, and (3) increased proteinuria after six days of exposure. We also observed different inflammatory markers associated with the development of IUGR or PE. We conclude that the detrimental effects of SHS or eCig treatment coincide with the length of maternal exposure. These results could be beneficial in understanding the long-term effects of SHS or eCig exposure in the development of placental diseases.<\/jats:p>","DOI":"10.3390\/cells13121009","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T08:49:03Z","timestamp":1718009343000},"page":"1009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Different Lengths of Gestational Exposure to Secondhand Smoke or e-Cigarette Vapor Induce the Development of Placental Disease Symptoms"],"prefix":"10.3390","volume":"13","author":[{"given":"Madison N.","family":"Kirkham","sequence":"first","affiliation":[{"name":"Lung and Placenta Laboratory, Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Cooper","sequence":"additional","affiliation":[{"name":"Lung and Placenta Laboratory, Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Broberg","sequence":"additional","affiliation":[{"name":"Lung and Placenta Laboratory, Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Robertson","sequence":"additional","affiliation":[{"name":"Lung and Placenta Laboratory, Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek","family":"Clarke","sequence":"additional","affiliation":[{"name":"Lung and Placenta Laboratory, Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7930-8160","authenticated-orcid":false,"given":"Brett E.","family":"Pickett","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Bikman","sequence":"additional","affiliation":[{"name":"Lung and Placenta Laboratory, Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0931-3025","authenticated-orcid":false,"given":"Paul R.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Lung and Placenta Laboratory, Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8818-8786","authenticated-orcid":false,"given":"Juan A.","family":"Arroyo","sequence":"additional","affiliation":[{"name":"Lung and Placenta Laboratory, Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/humupd\/dmaa053","article-title":"Adaptations of the human placenta to hypoxia: Op-portunities for interventions in fetal growth restriction","volume":"27","author":"Colson","year":"2021","journal-title":"Hum. Reprod. Update"},{"key":"ref_2","first-page":"2","article-title":"Classification of intrauterine growth retardation","volume":"12","author":"Brar","year":"1988","journal-title":"Semin. Perinatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1097\/00003081-199203000-00015","article-title":"Intrauterine Growth Retardation: Definition, Classification, and Etiology","volume":"35","author":"Pollack","year":"1992","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_4","first-page":"271","article-title":"Placental apoptosis in preeclampsia","volume":"96","author":"Allaire","year":"2000","journal-title":"Obstet. Gynecol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1161\/01.RES.0000024411.22110.AA","article-title":"Hypoxia-reoxygenation: A potent inducer of apop-totic changes in the human placenta and possible etiological factor in preeclampsia","volume":"90","author":"Hung","year":"2002","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lecarpentier, E., Tsatsaris, V., Goffinet, F., Cabrol, D., Sibai, B., and Haddad, B. (2013). Risk Factors of Superimposed Preeclampsia in Women with Essential Chronic Hypertension Treated before Pregnancy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062140"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.preghy.2010.10.013","article-title":"The role of obesity in preeclampsia","volume":"1","author":"Roberts","year":"2010","journal-title":"Pregnancy Hypertens"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2147\/IBPC.S50641","article-title":"Risk factors and effective management of preeclampsia","volume":"8","author":"Kenny","year":"2015","journal-title":"Integr. Blood Press. Control."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0002-9440(10)65123-1","article-title":"Preeclampsia is associated with widespread apoptosis of placental cy-totrophoblasts within the uterine wall","volume":"155","author":"DiFederico","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/S0002-9378(99)70341-8","article-title":"Cigarette smoking during pregnancy and risk of preeclampsia: A systematic review","volume":"181","author":"Althabe","year":"1999","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_11","first-page":"541","article-title":"Cigarette smoking and preeclampsia","volume":"81","author":"Edelstein","year":"1993","journal-title":"Obstet. Gynecol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1479-828X.2011.01387.x","article-title":"Recent cessation of smoking and its effect on pregnancy outcomes","volume":"52","author":"Bickerstaff","year":"2012","journal-title":"Aust. New Zealand J. Obstet. Gynaecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"805","DOI":"10.12891\/ceog2053.2015","article-title":"Antenatal counseling against passive smoking may improve birth weight for gestational age","volume":"42","author":"Akkar","year":"2015","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s00441-017-2691-z","article-title":"Inhibition of the receptor for advanced glycation end-products (RAGE) protects from secondhand smoke (SHS)-induced intrauterine growth restriction IUGR in mice","volume":"370","author":"Lewis","year":"2017","journal-title":"Cell Tissue Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1093\/aje\/kwv279","article-title":"Pas-sive smoke exposure as a risk factor for oral clefts\u2014A large international population-based study","volume":"183","author":"Kummet","year":"2016","journal-title":"Am. Jour-Nal Epidemiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1183\/13993003.01016-2015","article-title":"The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children","volume":"48","author":"Vardavas","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.jped.2015.08.010","article-title":"Influence of passive smoking on learning in elementary school","volume":"92","author":"Jorge","year":"2016","journal-title":"J. De Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1378\/chest.11-2443","article-title":"Short-term pulmonary effects of using an electronic cigarette: Impact on respiratory flow resistance, impedance, and ex-haled nitric oxide","volume":"141","author":"Vardavas","year":"2012","journal-title":"Chest"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Etter, J.-F. (2010). Electronic cigarettes: A survey of users. BMC Public Health, 10.","DOI":"10.1186\/1471-2458-10-231"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1158\/1055-9965.EPI-10-0288","article-title":"A Clinical Laboratory Model for Evaluating the Acute Effects of Electronic \u201cCigarettes\u201d: Nicotine Delivery Profile and Cardiovascular and Subjective Effects","volume":"19","author":"Vansickel","year":"2010","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_21","unstructured":"Gennimata, S.-A., Palamidas, A., Kaltsakas, G., Tsikrika, S., Vakali, S., Gratziou, C., and Koulouris, N. (2012). Acute effect of e-cigarette on pulmonary function in healthy subjects and smokers. Eur. Respir. J., 40."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1177\/1933719108329095","article-title":"Inflammation and Pregnancy","volume":"16","author":"Challis","year":"2009","journal-title":"Reprod. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Otani, N., Nakajima, K., Ishikawa, K., Ichiki, K., Ueda, T., Takesue, Y., Yamamoto, T., Tanimura, S., Shima, M., and Okuno, T. (2021). Changes in Cell-Mediated Immunity (IFN-\u03b3 and Granzyme B) Following Influenza Vaccination. Viruses, 13.","DOI":"10.3390\/v13061137"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1749-6632.2009.05133.x","article-title":"Th1 and Th17 cells: Adversaries and collaborators","volume":"1183","author":"Damsker","year":"2010","journal-title":"Ann. New York Acad. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1095\/biolreprod.108.073353","article-title":"Interferon gamma in successful pregnan-cies","volume":"80","author":"Murphy","year":"2009","journal-title":"Biology of reproduction"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1073\/pnas.86.2.656","article-title":"The interleukin 2 gene is expressed in the syncytiotrophoblast of the human placenta","volume":"86","author":"Boehm","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Deer, E., Amaral, L.M., Campbell, N., Fitzgerald, S., Herrock, O., Ibrahim, T., and LaMarca, B. (2021). Low dose of IL-2 nor-malizes hypertension and mitochondrial function in the RUPP rat model of placental ischemia. Cells, 10.","DOI":"10.3390\/cells10102797"},{"key":"ref_28","first-page":"4933","article-title":"IL-12, TNF-\u03b1, and hormonal changes during late pregnancy and early postpartum: Implications for auto-immune disease activity during these times","volume":"86","author":"Elenkov","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1097\/01.LAB.0000087589.37269.FC","article-title":"Regulation of interleu-kin 12 p40 and p70 production by blood and alveolar phagocytes during severe sepsis","volume":"83","author":"Ethuin","year":"2003","journal-title":"Lab. Investig."},{"key":"ref_30","first-page":"2505","article-title":"Expression of inflammatory cytokines in pla-centas from women with preeclampsia","volume":"86","author":"Benyo","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.placenta.2021.09.016","article-title":"TREM-1 amplifies trophoblastic inflammation via activating NF-\u03baB pathway during preeclampsia","volume":"115","author":"Xie","year":"2021","journal-title":"Placenta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jri.2012.05.004","article-title":"Interleukin-6 in pregnancy and gestational disorders","volume":"95","author":"Prins","year":"2012","journal-title":"J. Reprod. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1111\/cei.12608","article-title":"Interleukin-1 family cytokines and their regulatory proteins in normal pregnancy and pre-eclampsia. Clin","volume":"181","author":"Southcombe","year":"2015","journal-title":"Exp. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1136\/bmj.321.7258.424","article-title":"Th1 and Th2 responses: What are they?","volume":"321","author":"Berger","year":"2000","journal-title":"Bmj"},{"key":"ref_35","first-page":"548539","article-title":"T helper (Th) cell profiles in pregnancy and recurrent pregnancy losses: Th1\/Th2\/Th9\/Th17\/Th22\/Tfh cells","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.4049\/jimmunol.1202246","article-title":"IL-4 in the Brain: A Cytokine To Remember","volume":"189","author":"Gadani","year":"2012","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1046\/j.1365-2567.1997.00139.x","article-title":"Localization of IL-4 and IL-4 receptors in the human term placenta, decidua and amniochorionic membranes","volume":"90","author":"Vince","year":"1997","journal-title":"Immunology"},{"key":"ref_38","first-page":"3256","article-title":"miR-320a upregulation contributes to the development of preeclampsia by inhibiting the growth and invasion of trophoblast cells by targeting interleukin 4","volume":"20","author":"Xie","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103379","DOI":"10.1016\/j.jri.2021.103379","article-title":"Trophoblast-derived interleukin 9 mediates immune cell conversion and con-tributes to maternal-fetal tolerance","volume":"148","author":"Sun","year":"2021","journal-title":"J. Reprod. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/j.1600-0897.1998.tb00419.x","article-title":"Expression and Localization of the Th2-type Cytokine Interleukin-13 and Its Receptor in the Placenta During Human Pregnancy","volume":"40","author":"Dealtry","year":"1998","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"98","DOI":"10.12891\/ceog3295.2017","article-title":"Pro-inflammatory and anti-inflammatory cytokine profiles in fetal growth restriction","volume":"44","author":"Raghupathy","year":"2017","journal-title":"Clin. Exp. Obstet. Gynecol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/iub.361","article-title":"The multifaceted effects of granulocyte colony-stimulating factor in immunomod-ulation and potential roles in intestinal immune homeostasis","volume":"62","author":"Martins","year":"2010","journal-title":"IUBMB Life"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"471","DOI":"10.3389\/fendo.2019.00471","article-title":"CXCL13 and Its Receptor CXCR5 in Cancer: Inflammation, Immune Response, and Beyond","volume":"10","author":"Kazanietz","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.4049\/jimmunol.0803834","article-title":"Villitis of Unknown Etiology Is Associated with a Distinct Pattern of Chemokine Up-Regulation in the Feto-Maternal and Placental Compartments: Implications for Conjoint Maternal Allograft Rejection and Maternal Anti-Fetal Graft-versus-Host Disease","volume":"182","author":"Kim","year":"2009","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1093\/humrep\/det060","article-title":"Control of extravillous trophoblast function by the eotaxins CCL11, CCL24 and CCL26","volume":"28","author":"Chau","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Ullah, A., Zhao, J., Singla, R.K., and Shen, B. (2023). Pathophysiological impact of CXC and CX3CL1 chemokines in preeclampsia and gestational diabetes mellitus. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1272536"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, Z., He, J., Jin, P., Ran, Y., Yin, N., and Qi, H. (2023). CCL21\/CCR7 Axis Contributes to Trophoblastic Cell Migration and Invasion in Preeclampsia by Affecting the Epithelial Mesenchymal Transition via the ERK1\/2 Signaling Path-way. Biology, 12.","DOI":"10.3390\/biology12020150"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e12990","DOI":"10.1111\/aji.12990","article-title":"XCL 1-XCR 1 pathway promotes trophoblast inva-sion at maternal-fetal interface by inducing MMP-2\/MMP-9 activity","volume":"80","author":"Zhang","year":"2018","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Krivoku\u0107a, M.J., Viloti\u0107, A., Nacka-Aleksi\u0107, M., Pirkovi\u0107, A., \u0106uji\u0107, D., Legner, J., Dekanski, D., and Boji\u0107-Trbojevi\u0107, \u017d. (2021). Galectins in Early Pregnancy and Pregnancy-Associated Pathologies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010069"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Wallach, D. (2018). The Tumor Necrosis Factor Family: Family Conventions and Private Idiosyncrasies. Cold Spring Harb. Perspect. Biol., 10.","DOI":"10.1101\/cshperspect.a028431"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jang, D.-I., Lee, A.-H., Shin, H.-Y., Song, H.-R., Park, J.-H., Kang, T.-B., Lee, S.-R., and Yang, S.-H. (2021). The Role of Tumor Necrosis Factor Alpha (TNF-\u03b1) in Autoimmune Disease and Current TNF-\u03b1 Inhibitors in Therapeutics. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052719"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Fakhr, Y., Koshti, S., Habibyan, Y.B., Webster, K., and Hemmings, D.G. (2022). Tumor Necrosis Factor-\u03b1 Induces a Preeclamptic-like Phenotype in Placental Villi via Sphingosine Kinase 1 Activation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073750"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"829862","DOI":"10.1155\/2014\/829862","article-title":"Intrauterine growth restriction increases TNF\u03b1 and activates the unfolded protein response in male rat pups","volume":"2014","author":"Riddle","year":"2014","journal-title":"J. Obes."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"382","DOI":"10.3389\/fimmu.2016.00382","article-title":"Fas\u2013Fas Ligand: Checkpoint of T Cell Functions in Multiple Sclerosis","volume":"7","author":"Volpe","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.2353\/ajpath.2008.071139","article-title":"Signaling Pathways for B Cell-Activating Factor (BAFF) and a Proliferation-Inducing Ligand (APRIL) in Human Placenta","volume":"172","author":"Langat","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1080\/14728222.2018.1512588","article-title":"Glucocorticoid-induced TNFR-related gene (GITR) as a therapeutic tar-get for immunotherapy","volume":"22","author":"Riccardi","year":"2018","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_57","first-page":"1","article-title":"The Role of Decorin in Autoimmune and Inflammatory Diseases","volume":"2022","author":"Dong","year":"2022","journal-title":"J. Immunol. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1158\/1541-7786.MCR-20-0799","article-title":"mDKN-01, a Novel Anti-DKK1 mAb, Enhances Innate Immune Responses in the Tumor Microenvironment","volume":"19","author":"Haas","year":"2020","journal-title":"Mol. Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.placenta.2019.03.001","article-title":"Down-regulation of DKK1 and Wnt1\/\u03b2-catenin pathway by increased homeobox B7 resulted in cell differentiation suppression of intrauterine fetal growth retardation in human placenta","volume":"80","author":"Huang","year":"2019","journal-title":"Placenta"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-85001-2","article-title":"Anti-CD321 antibody immunotherapy protects liver against ischemia and reperfusion-induced injury","volume":"11","author":"Yin","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_61","first-page":"224","article-title":"ACE and ACE2 in inflammation: A tale of two enzymes","volume":"13","author":"Chambers","year":"2014","journal-title":"Inflamma-Tion Allergy-Drug Targets (Former. Curr. Drug Targets-Inflamm. Allergy)(Discontin. )"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"S55","DOI":"10.1016\/j.placenta.2011.09.019","article-title":"IFPA Award in Placentology lecture: Molecular regulation of human trophoblast in-vasion","volume":"33","author":"Pollheimer","year":"2012","journal-title":"Placenta"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ridder, A., Giorgione, V., Khalil, A., and Thilaganathan, B. (2019). Preeclampsia: The Relationship between Uterine Artery Blood Flow and Trophoblast Function. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133263"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ejogrb.2004.11.020","article-title":"Blood pressure is elevated in normotensive pregnant women with intrauterine growth restriction","volume":"122","author":"Tranquilli","year":"2005","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e13598","DOI":"10.1111\/aji.13598","article-title":"Inflammasome activation in preeclampsia and intrauterine growth restriction","volume":"88","author":"Silber","year":"2022","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.placenta.2015.05.016","article-title":"Aberrant maternal inflammation as a cause of pregnancy complications: A potential therapeutic target?","volume":"36","author":"Cotechini","year":"2015","journal-title":"Placenta"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1046\/j.1365-2249.1999.00997.x","article-title":"Quantitative analysis of peripheral blood Th0, Th1, Th2 and the Th1: Th2 cell ratio during normal human pregnancy and preeclampsia","volume":"117","author":"Saito","year":"1999","journal-title":"Clin. Ex-Perimental Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1007\/s43032-022-01110-x","article-title":"The Role of Interferon (IFN)-\u03b3 in Extravillous Trophoblast Cell (EVT) Invasion and Preeclampsia Progression","volume":"30","author":"Nurzadeh","year":"2022","journal-title":"Reprod. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1111\/aji.12298","article-title":"Interleukin-18 and interferon gamma levels in preeclampsia: A systematic re-view and meta-analysis","volume":"72","author":"Yang","year":"2014","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13293-020-00345-0","article-title":"Inves-tigation of interleukin-2-mediated changes in blood pressure, fetal growth restriction, and innate immune acti-vation in normal pregnant rats and in a preclinical rat model of preeclampsia","volume":"12","author":"Cunningham","year":"2021","journal-title":"Biol. Sex Differ."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nri1001","article-title":"Interleukin-12 and the regulation of innate resistance and adaptive immunity","volume":"3","author":"Trinchieri","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Gibot, S. (2006). Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia and severe sepsis. Seminars in Respiratory and Critical Care Medicine, Thieme Medical Publishers, Inc.","DOI":"10.1055\/s-2006-933671"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"7547","DOI":"10.1073\/pnas.83.19.7547","article-title":"Cloning and expression of cDNA for human diazepam binding inhibitor, a natural ligand of an allosteric regulatory site of the gamma-aminobutyric acid type A receptor","volume":"83","author":"Gray","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1177\/1933719113503406","article-title":"TREM-1 Expression Is Increased in Human Placentas From Severe Early-Onset Preeclamptic Pregnancies Where It May Be Involved in Syncytialization","volume":"21","author":"Lim","year":"2013","journal-title":"Reprod. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.immunol.021908.132612","article-title":"Immunological and Inflammatory Functions of the Interleukin-1 Family","volume":"27","author":"Dinarello","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1182\/blood-2010-07-273417","article-title":"Interleukin-1 in the pathogenesis and treatment of inflammatory diseases","volume":"117","author":"Dinarello","year":"2011","journal-title":"Blood"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e13316","DOI":"10.1111\/aji.13316","article-title":"Specific inflammatory profile in each pregnancy complication: A comparative study","volume":"84","author":"Brien","year":"2020","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Zhang, S., Ding, J., Zhang, Y., Liu, S., Yang, J., and Yin, T. (2022). Regulation and Function of Chemokines at the Maternal\u2013Fetal Interface. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.826053"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1080\/10641963.2022.2043891","article-title":"Neutrophil count is a useful marker to predict the severity of preeclampsia","volume":"44","author":"Liu","year":"2022","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.micinf.2011.10.003","article-title":"XCL1 and XCR1 in the immune system","volume":"14","author":"Lei","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s12013-015-0690-9","article-title":"Expression of the Lymphocyte Chemokine XCL1 in Lung Tissue of COPD Mice, and Its Relationship to CD4+\/CD8+ Ratio and IL-2","volume":"73","author":"Zhuo","year":"2015","journal-title":"Cell Biochem. Biophys."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"pgad247","DOI":"10.1093\/pnasnexus\/pgad247","article-title":"Maternal-derived galectin-1 shapes the placenta niche through Sda terminal glycosylation: Implication for preeclampsia","volume":"2","author":"Xie","year":"2023","journal-title":"PNAS Nexus"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12884-020-03477-8","article-title":"Galectin-1 expression in the serum and placenta of pregnant women with fetal growth restriction and its significance","volume":"21","author":"Jin","year":"2021","journal-title":"BMC Pregnancy Childbirth"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0301-2115(00)00321-3","article-title":"Increased produc-tion of tumor necrosis factor-\u03b1 TNF-\u03b1 by IUGR human placentae","volume":"94","author":"Holcberg","year":"2001","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1387\/ijdb.082831jh","article-title":"Immunoregulatory molecules in human placentas: Potential for diverse roles in pregnancy","volume":"54","author":"Hunt","year":"2010","journal-title":"Int. J. Dev. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.3109\/14767058.2015.1038702","article-title":"Fas and FasL expression in placentas complicated with intrauterine growth retardation with and without preeclampsia","volume":"29","author":"Karara","year":"2015","journal-title":"J. Matern. Neonatal Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/sj.cdd.4401179","article-title":"Signaling and transcriptional control of Fas ligand gene expression","volume":"10","author":"Kavurma","year":"2003","journal-title":"Cell Death Differ."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Nocentini, G., Cuzzocrea, S., Genovese, T., Bianchini, R., Mazzon, E., Ronchetti, S., Esposito, E., di Paola, R., Bramanti, P., and Riccardi, C. GITR-FC FUSION PROTEIN INHIBITS GITR TRIGGERING AND PROTECTS FROM THE INFLAMMATORY RESPONSE FOLLOWING SPINAL CORD INJURY. Molecular Pharmacology, 2008.","DOI":"10.1124\/mol.107.044354"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"361.e1","DOI":"10.1016\/j.ajog.2016.03.020","article-title":"Decorin over-expression by decidual cells in preeclampsia: A potential blood biomarker","volume":"215","author":"Siddiqui","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Halari, C.D., Zheng, M., and Lala, P.K. (2021). Roles of two small leucine-rich proteoglycans decorin and biglycan in preg-nancy and pregnancy-associated diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910584"},{"key":"ref_91","first-page":"190","article-title":"Human placental trophoblast invasion and differentiation: A particular focus on Wnt signaling","volume":"4","author":"Pollheimer","year":"2013","journal-title":"Front. Genet."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/j.fshw.2022.06.011","article-title":"Angiotensin I converting enzyme (ACE) inhibitory activity and antihypertensive effects of rice peptides","volume":"11","author":"Dong","year":"2022","journal-title":"Food Sci. Hum. Wellness"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/12\/1009\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:56:09Z","timestamp":1760108169000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/12\/1009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,9]]},"references-count":92,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["cells13121009"],"URL":"https:\/\/doi.org\/10.3390\/cells13121009","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,9]]}}}