{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T14:15:51Z","timestamp":1780668951728,"version":"3.54.1"},"reference-count":88,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T00:00:00Z","timestamp":1724803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Oxidative stress (OS) and apoptosis are critical factors in placental development and function. Their interplay influences trophoblast proliferation, differentiation, and invasion, as well as vascular development. An imbalance between these processes can lead to pregnancy-related disorders such as preeclampsia, intrauterine growth restriction, and even spontaneous abortion. Our study seeks to elucidate the associations between preventive antioxidant\/protective OS response factors\u2014glutathione (GSH), MutT Homolog 1 (MTH1), and apoptotic regulation modulators\u2014tumor protein p53 and B-cell lymphoma (Bcl-2) transcripts, in the context of spontaneous abortion (30 samples) versus elective termination of pregnancy (20 samples), using immunohistochemistry (IHC) to determine their proteomic expression in chorionic villi within abortive fetal placenta tissue samples. Herein, comparative statistical analyses revealed that both OS response factors, GSH and MTH1, were significantly under-expressed in spontaneous abortion cases as compared to elective. Conversely, for apoptotic regulators, p53 expression was significantly higher in spontaneous abortion cases, whereas Bcl-2 expression was significantly lower in spontaneous abortion cases. These findings suggest that a strong pro-apoptotic signal is prevalent within spontaneous abortion samples, alongside reduced anti-apoptotic protection, depleted antioxidant defenses and compromised oxidative DNA damage prevention\/repair, as compared to elective abortion controls. Herein, our hypothesis that OS and apoptosis are closely linked processes contributing to placental dysfunction and spontaneous abortion was thus seemingly corroborated. Our results further highlight the importance of maintaining redox homeostasis and apoptotic regulation for a successful pregnancy. Understanding the mechanisms underlying this interplay is essential for developing potential therapies to manage OS, promote placentation, and avoid unwanted apoptosis, ultimately improving pregnancy outcomes. Antioxidant supplementation, modulation of p53 activity, and the enhancement of DNA repair mechanisms may represent potential approaches to mitigate OS and apoptosis in the placenta. Further research is needed to explore these strategies and their efficacy in preventing spontaneous abortion.<\/jats:p>","DOI":"10.3390\/life14091074","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T03:57:06Z","timestamp":1724817426000},"page":"1074","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antioxidant Defenses, Oxidative Stress Responses, and Apoptosis Modulation in Spontaneous Abortion: An Immunohistochemistry Analysis of First-Trimester Chorionic Villi"],"prefix":"10.3390","volume":"14","author":[{"given":"Ioana","family":"Vornic","sequence":"first","affiliation":[{"name":"Doctoral School, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania"},{"name":"Discipline of Gynecology, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru","family":"Nesiu","sequence":"additional","affiliation":[{"name":"Discipline of Urology, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria","family":"Ardelean","sequence":"additional","affiliation":[{"name":"Doctoral School, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania"},{"name":"Discipline of Gynecology, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana Cristina","family":"Todut","sequence":"additional","affiliation":[{"name":"Doctoral School, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania"},{"name":"Discipline of Gynecology, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria Cristina","family":"Pasare","sequence":"additional","affiliation":[{"name":"Doctoral School, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania"},{"name":"Discipline of Gynecology, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Onel","sequence":"additional","affiliation":[{"name":"Doctoral School, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania"},{"name":"Discipline of Gynecology, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ionu\u021b Daniel","family":"Raducan","sequence":"additional","affiliation":[{"name":"Doctoral School, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7158-2579","authenticated-orcid":false,"given":"Cristian George","family":"Furau","sequence":"additional","affiliation":[{"name":"Discipline of Gynecology, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Novacescu, D., Nesiu, A., Bardan, R., Latcu, S., Dema, V., Croitor, A., Raica, M., Cut, T.G., Walter, J., and Cumpanas, A. (2023). Rats, Neuregulins and Radical Prostatectomy: A Conceptual Overview. J. Clin. Med., 12.","DOI":"10.3390\/jcm12062208"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Latcu, S., Novacescu, D., Buciu, V.-B., Dumitru, C.-S., Ceau\u015fu, R., Raica, M., Cut, T.G., Ilina, R., Malita, D., and Tarta, C. (2023). The Cavernous Nerve Injury Rat Model: A Pictorial Essay on Post-Radical Prostatectomy Erectile Dysfunction Research. Life, 13.","DOI":"10.3390\/life13122337"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.51847\/CO2qttSgIN","article-title":"Assessing the Role of Bcl-2 and P53 in Apoptotic Mechanisms in Spontaneous Abortions","volume":"15","author":"Vornic","year":"2024","journal-title":"Pharmacophore"},{"key":"ref_4","unstructured":"Pascual, Z.N., and Langaker, M.D. (2024). Physiology, Pregnancy. StatPearls, StatPearls Publishing."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.thromres.2004.06.038","article-title":"Growth and Function of the Normal Human Placenta","volume":"114","author":"Gude","year":"2004","journal-title":"Thromb. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sharma, L., Kaur, J., and Shukla, G. (2012). Role of Oxidative Stress and Apoptosis in the Placental Pathology of Plasmodium Berghei Infected Mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032694"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Burton, G.J., and Fowden, A.L. (2015). The Placenta: A Multifaceted, Transient Organ. Philos. Trans. R. Soc. Lond. B Biol. Sci., 370.","DOI":"10.1098\/rstb.2014.0066"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wu, F., Tian, F.-J., and Lin, Y. (2015). Oxidative Stress in Placenta: Health and Diseases. Biomed. Res. Int., 2015.","DOI":"10.1155\/2015\/293271"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Afzal, S., Abdul Manap, A.S., Attiq, A., Albokhadaim, I., Kandeel, M., and Alhojaily, S.M. (2023). From Imbalance to Impairment: The Central Role of Reactive Oxygen Species in Oxidative Stress-Induced Disorders and Therapeutic Exploration. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1269581"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-1-4614-3573-0_6","article-title":"Molecular Mechanisms of Superoxide Production by the Mitochondrial Respiratory Chain","volume":"748","author":"Brandt","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1124\/pr.110.002980","article-title":"NADPH Oxidase-Mediated Redox Signaling: Roles in Cellular Stress Response, Stress Tolerance, and Tissue Repair","volume":"63","author":"Jiang","year":"2011","journal-title":"Pharmacol. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Aranguren, L.C., Prada, C.E., Ria\u00f1o-Medina, C.E., and Lopez, M. (2014). Endothelial Dysfunction and Preeclampsia: Role of Oxidative Stress. Front. Physiol., 5.","DOI":"10.3389\/fphys.2014.00372"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1016\/S0002-9440(10)64849-3","article-title":"Onset of Maternal Arterial Blood Flow and Placental Oxidative Stress","volume":"157","author":"Jauniaux","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S1028-4559(09)60224-2","article-title":"Hypoxia and Reoxygenation: A Possible Mechanism for Placental Oxidative Stress in Preeclampsia","volume":"45","author":"Hung","year":"2006","journal-title":"Taiwan J. Obs. Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3453","DOI":"10.1113\/jphysiol.2009.173252","article-title":"Intrauterine Growth Restriction, Human Placental Development and Trophoblast Cell Death","volume":"587","author":"Scifres","year":"2009","journal-title":"J. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1053\/plac.1999.0524","article-title":"Regulation of Placental Vascular Endothelial Growth Factor (VEGF) and Placenta Growth Factor (PIGF) and Soluble Flt-1 by Oxygen\u2014A Review","volume":"21","author":"Ahmed","year":"2000","journal-title":"Placenta"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Forsythe, J.A., Jiang, B.H., Iyer, N.V., Agani, F., Leung, S.W., Koos, R.D., and Semenza, G.L. (1996). Activation of Vascular Endothelial Growth Factor Gene Transcription by Hypoxia-Inducible Factor 1. Mol. Cell. Biol., 16.","DOI":"10.1128\/MCB.16.9.4604"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3300","DOI":"10.1002\/art.38822","article-title":"Redox-Mediated Angiogenesis in the Hypoxic Joint of Inflammatory Arthritis","volume":"66","author":"Biniecka","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"H1563","DOI":"10.1152\/ajpheart.01081.2005","article-title":"Angiopoietin-1-Induced Angiogenesis Is Modulated by Endothelial NADPH Oxidase","volume":"291","author":"Chen","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.canlet.2008.02.044","article-title":"Reactive Oxygen Species and Angiogenesis: NADPH Oxidase as Target for Cancer Therapy","volume":"266","author":"Nakamura","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"H1664","DOI":"10.1152\/ajpheart.01138.2006","article-title":"NADPH Oxidase Modulates Myocardial Akt, ERK1\/2 Activation, and Angiogenesis after Hypoxia-Reoxygenation","volume":"292","author":"Chen","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Pereira, R.D., Long, N.E.D., Wang, R.C., Yazdi, F.T., Holloway, A.C., and Raha, S. (2015). Angiogenesis in the Placenta: The Role of Reactive Oxygen Species Signaling. BioMed Res. Int., 2015.","DOI":"10.1155\/2015\/814543"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1053\/plac.2002.0850","article-title":"The Human Placental Bed Revisited","volume":"23","author":"Lyall","year":"2002","journal-title":"Placenta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0002-9440(10)63803-5","article-title":"Trophoblastic Oxidative Stress in Relation to Temporal and Regional Differences in Maternal Placental Blood Flow in Normal and Abnormal Early Pregnancies","volume":"162","author":"Jauniaux","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1053\/plac.1999.0522","article-title":"Oxygen and Placental Development during the First Trimester: Implications for the Pathophysiology of Pre-Eclampsia","volume":"21","author":"Caniggia","year":"2000","journal-title":"Placenta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1095\/biolreprod62.3.739","article-title":"Extracellular Matrix Composition and Hypoxia Regulate the Expression of HLA-G and Integrins in a Human Trophoblast Cell Line","volume":"62","author":"Kilburn","year":"2000","journal-title":"Biol. Reprod."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhao, H., Jiang, Y., Cao, Q., Hou, Y., and Wang, C. (2012). Role of Integrin Switch and Transforming Growth Factor Beta 3 in Hypoxia-Induced Invasion Inhibition of Human Extravillous Trophoblast Cells. Biol. Reprod., 87.","DOI":"10.1095\/biolreprod.112.099937"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.placenta.2011.06.023","article-title":"Hypoxia Inhibits Invasion of Extravillous Trophoblast Cells through Reduction of Matrix Metalloproteinase (MMP)-2 Activation in the Early First Trimester of Human Pregnancy","volume":"32","author":"Onogi","year":"2011","journal-title":"Placenta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1242\/dev.120.12.3657","article-title":"Integrin Switching Regulates Normal Trophoblast Invasion","volume":"120","author":"Damsky","year":"1994","journal-title":"Development"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"C776","DOI":"10.1152\/ajpcell.00507.2009","article-title":"Autophagy in Health and Disease. 1. Regulation and Significance of Autophagy: An Overview","volume":"298","author":"Mehrpour","year":"2010","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1146\/annurev-genet-102808-114910","article-title":"Regulation Mechanisms and Signaling Pathways of Autophagy","volume":"43","author":"He","year":"2009","journal-title":"Annu. Rev. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1152\/physrev.00030.2009","article-title":"Regulation of Mammalian Autophagy in Physiology and Pathophysiology","volume":"90","author":"Ravikumar","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Thorburn, A. (2014). Autophagy and Its Effects: Making Sense of Double-Edged Swords. PLoS Biol., 12.","DOI":"10.1371\/journal.pbio.1001967"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1128\/MCB.00166-09","article-title":"Hypoxia-Induced Autophagy Is Mediated through Hypoxia-Inducible Factor Induction of BNIP3 and BNIP3L via Their BH3 Domains","volume":"29","author":"Bellot","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/sj.cdd.4402233","article-title":"Oxidative Stress Induces Autophagic Cell Death Independent of Apoptosis in Transformed and Cancer Cells","volume":"15","author":"Chen","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"303","DOI":"10.4161\/auto.22927","article-title":"Impaired Autophagy by Soluble Endoglin, under Physiological Hypoxia in Early Pregnant Period, Is Involved in Poor Placentation in Preeclampsia","volume":"9","author":"Nakashima","year":"2013","journal-title":"Autophagy"},{"key":"ref_37","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":"Mediat. Inflamm."},{"key":"ref_38","first-page":"8","article-title":"Glutathione!","volume":"13","author":"Pizzorno","year":"2014","journal-title":"Integr. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Dahma, G., Reddy, G., Craina, M., Dumitru, C., Popescu, A., Stelea, L., Neamtu, R., Gluhovschi, A., Nitu, R., and Maghiari, A. (2023). The Effects of Vitamin D Supplementation before 20 Weeks of Gestation on Preeclampsia: A Systematic Review. J. Pers. Med., 13.","DOI":"10.3390\/jpm13060996"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Aouache, R., Biquard, L., Vaiman, D., and Miralles, F. (2018). Oxidative Stress in Preeclampsia and Placental Diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051496"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4761","DOI":"10.1074\/jbc.RA120.012636","article-title":"MutT Homologue 1 (MTH1) Removes N6-Methyl-dATP from the dNTP Pool","volume":"295","author":"Scaletti","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"883","DOI":"10.3892\/mmr.2012.763","article-title":"DNA Methylation in the Human Placenta and Fetal Growth (Review)","volume":"5","author":"KOUKOURA","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Guan, D., Sun, W., Gao, M., Chen, Z., and Ma, X. (2024). Immunologic Insights in Recurrent Spontaneous Abortion: Molecular Mechanisms and Therapeutic Interventions. Biomed. Pharmacother., 177.","DOI":"10.1016\/j.biopha.2024.117082"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1600-0897.2010.00837.x","article-title":"Placental Apoptosis in Health and Disease","volume":"64","author":"Sharp","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Raguema, N., Moustadraf, S., and Bertagnolli, M. (2020). Immune and Apoptosis Mechanisms Regulating Placental Development and Vascularization in Preeclampsia. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00098"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Lokeswara, A.W., Hiksas, R., Irwinda, R., and Wibowo, N. (2021). Preeclampsia: From Cellular Wellness to Inappropriate Cell Death, and the Roles of Nutrition. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.726513"},{"key":"ref_47","unstructured":"Sionov, R.V., Hayon, I.L., and Haupt, Y. (2013). The Regulation of P53 Growth Suppression. Madame Curie Bioscience Database [Internet], Landes Bioscience."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"994","DOI":"10.3390\/cancers3010994","article-title":"Role of P53 in Cell Death and Human Cancers","volume":"3","author":"Ozaki","year":"2011","journal-title":"Cancers"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Qian, S., Wei, Z., Yang, W., Huang, J., Yang, Y., and Wang, J. (2022). The Role of BCL-2 Family Proteins in Regulating Apoptosis and Cancer Therapy. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.985363"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.3390\/encyclopedia2040111","article-title":"Apoptosis Regulators Bcl-2 and Caspase-3","volume":"2","author":"Hussar","year":"2022","journal-title":"Encyclopedia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.diabres.2005.12.014","article-title":"Changes in Apoptosis and Bcl-2 Expression in Human Hyperglycemic, Term Placental Trophoblast","volume":"73","author":"Sgarbosa","year":"2006","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3892\/etm.2013.1399","article-title":"Apoptosis and P53 Expression in the Placental Villi of Females with Unexplained Recurrent Spontaneous Abortion","volume":"7","author":"Wei","year":"2014","journal-title":"Exp. Ther. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1007\/s11010-022-04499-w","article-title":"Placental Oxidative Stress and Monoamine Oxidase Expression Are Increased in Severe Preeclampsia: A Pilot Study","volume":"477","author":"Bina","year":"2022","journal-title":"Mol. Cell. Biochem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1089\/ars.2014.5851","article-title":"Endoplasmic Reticulum Stress and Oxidative Stress in Cell Fate Decision and Human Disease","volume":"21","author":"Cao","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Chong, W.C., Shastri, M.D., and Eri, R. (2017). Endoplasmic Reticulum Stress and Oxidative Stress: A Vicious Nexus Implicated in Bowel Disease Pathophysiology. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040771"},{"key":"ref_56","first-page":"2505","article-title":"Association between Fetal Chromosomal Abnormalities and the Frequency of Spontaneous Abortions","volume":"19","author":"Yang","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Iordache, O., Anastasiu-Popov, D., Anastasiu, D., Craina, M., Dahma, G., Sacarin, G., Silaghi, C., Cosmin, C., Daniluc, R., and Hinoveanu, D. (2022). A Retrospective Assessment of Thrombophilia in Pregnant Women with First and Second Trimester Pregnancy Loss. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph192416500"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Matei, S.-C., Dumitru, C.\u0218., Opri\u021boiu, A.-I., Marian, L., Murariu, M.-S., and Olariu, S. (2023). Female Gonadal Venous Insufficiency in a Clinical Presentation Which Suggested an Acute Abdomen-A Case Report and Literature Review. Medicina, 59.","DOI":"10.3390\/medicina59050884"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Mocanu, A., Stoian, D., Craciunescu, E., Ciohat, I., Catalin, M., Navolan, D., Vilibi\u0107-\u010cavlek, T., Stevanovic, V., Nemescu, D., and Forga, M. (2022). The Impact of Latent Toxoplasma Gondii Infection on Spontaneous Abortion History and Pregnancy Outcomes: A Large-Scale Study. Microorganisms, 10.","DOI":"10.3390\/microorganisms10101944"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Moza, A., Bernad, E., Lungeanu, D., Craina, M., Bernad, B., Hogea, L., Paul, C., Muresan, C., Nitu, R., and Iacob, D. (2023). Pregnancy Outcomes in SARS-CoV-2-Positive Patients: A 20-Month Retrospective Analysis of Delivery Cases. Medicina, 59.","DOI":"10.3390\/medicina59020341"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Enache, A., Ciocan, V., Muresan, C.O., Cut, T.G., Novacescu, D., Paul, C., Andreescu, N., Mihailescu, A., Raica, M., and Dumache, R. (2021). Postmortem Documentation of SARS-CoV-2 in Utero and Postpartum Transmission, through Amniotic Fluid, Placental, and Pulmonary Tissue RT-PCR. Appl. Sci., 11.","DOI":"10.3390\/app11209505"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Moza, A., Duica, F., Antoniadis, P., Bernad, E., Lungeanu, D., Craina, M., Bernad, B., Paul, C., Muresan, C., and Nitu, R. (2023). Outcome of Newborns with Confirmed or Possible SARS-CoV-2 Vertical Infection\u2014A Scoping Review. Diagnostics, 13.","DOI":"10.3390\/diagnostics13020245"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1007\/s11010-022-04415-2","article-title":"Impairment of Mitochondrial Respiration in Platelets and Placentas: A Pilot Study in Preeclamptic Pregnancies","volume":"477","author":"Bina","year":"2022","journal-title":"Mol. Cell. Biochem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1515\/JPM.2005.085","article-title":"The Role of Fas Mediated Apoptosis in Preeclampsia","volume":"33","author":"Neale","year":"2005","journal-title":"J. Perinat. Med."},{"key":"ref_65","first-page":"45","article-title":"Placental Apoptosis in Preeclampsia, Intrauterine Growth Retardation, and HELLP Syndrome: An Immunohistochemical Study with Caspase-3 and Bcl-2","volume":"40","author":"Cali","year":"2013","journal-title":"Clin. Exp. Obs. Gynecol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1089\/15230860260196209","article-title":"Redox Control of Cell Death","volume":"4","author":"Ueda","year":"2002","journal-title":"Antioxid. Redox Signal."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1247\/csf.28.23","article-title":"Roles of MAPKKK ASK1 in Stress-Induced Cell Death","volume":"28","author":"Takeda","year":"2003","journal-title":"Cell Struct. Funct."},{"key":"ref_68","first-page":"959","article-title":"Opposing Role of JNK-P38 Kinase and ERK1\/2 in Hydrogen Peroxide-Induced Oxidative Damage of Human Trophoblast-like JEG-3 Cells","volume":"7","author":"Tang","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Sharp, A.N., Heazell, A.E.P., Baczyk, D., Dunk, C.E., Lacey, H.A., Jones, C.J.P., Perkins, J.E., Kingdom, J.C.P., Baker, P.N., and Crocker, I.P. (2014). Preeclampsia Is Associated with Alterations in the P53-Pathway in Villous Trophoblast. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087621"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e305","DOI":"10.1038\/cddis.2012.44","article-title":"The Double Life of MULE in Preeclamptic and IUGR Placentae","volume":"3","author":"Rolfo","year":"2012","journal-title":"Cell Death Dis."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Novacescu, D., Cut, T.G., Cumpanas, A.A., Bratosin, F., Ceausu, R.A., and Raica, M. (2022). Novel Expression of Thymine Dimers in Renal Cell Carcinoma, Demonstrated through Immunohistochemistry. Biomedicines, 10.","DOI":"10.3390\/biomedicines10112673"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Novacescu, D., Cut, T.G., Cumpanas, A.A., Latcu, S.C., Bardan, R., Ferician, O., Secasan, C.-C., Rusmir, A., and Raica, M. (2022). Evaluating Established Roles, Future Perspectives and Methodological Heterogeneity for Wilms\u2019 Tumor 1 (WT1) Antigen Detection in Adult Renal Cell Carcinoma, Using a Novel N-Terminus Targeted Antibody (Clone WT49). Biomedicines, 10.","DOI":"10.3390\/biomedicines10040912"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Novacescu, D., Feciche, B.O., Cumpanas, A.A., Bardan, R., Rusmir, A.V., Bitar, Y.A., Barbos, V.I., Cut, T.G., Raica, M., and Latcu, S.C. (2022). Contemporary Clinical Definitions, Differential Diagnosis, and Novel Predictive Tools for Renal Cell Carcinoma. Biomedicines, 10.","DOI":"10.3390\/biomedicines10112926"},{"key":"ref_74","first-page":"277","article-title":"Clinical Significance of Her2\/Neu Overexpression in Urothelial Carcinomas","volume":"51","author":"Alexa","year":"2010","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Latcu, S., Bardan, R., Cumpanas, A., Barbos, V., Baderca, F., Gaje, P., Ceau\u015fu, R., Comsa, S., Dumitru, C.-S., and Dumache, R. (2024). Immunotherapy Applications for Thymine Dimers and WT1 Antigen in Renal Cancers: A Comparative Statistical Analysis. J. Pers. Med., 14.","DOI":"10.3390\/jpm14060557"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/sj.cdd.4401962","article-title":"The P53-Bcl-2 Connection","volume":"13","author":"Hemann","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1073\/pnas.2627984100","article-title":"PUMA Mediates the Apoptotic Response to P53 in Colorectal Cancer Cells","volume":"100","author":"Yu","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"9333","DOI":"10.1073\/pnas.0403286101","article-title":"Suppression of Tumorigenesis by the P53 Target PUMA","volume":"101","author":"Hemann","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1101\/gad.1103603","article-title":"Integral Role of Noxa in P53-Mediated Apoptotic Response","volume":"17","author":"Shibue","year":"2003","journal-title":"Genes Dev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6164","DOI":"10.1073\/pnas.0401471101","article-title":"Bim Is a Suppressor of Myc-Induced Mouse B Cell Leukemia","volume":"101","author":"Egle","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/nature03845","article-title":"Evasion of the P53 Tumour Surveillance Network by Tumour-Derived MYC Mutants","volume":"436","author":"Hemann","year":"2005","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.dnarep.2006.03.003","article-title":"MTH1, an Oxidized Purine Nucleoside Triphosphatase, Prevents the Cytotoxicity and Neurotoxicity of Oxidized Purine Nucleotides","volume":"5","author":"Nakabeppu","year":"2006","journal-title":"DNA Repair."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1016\/j.apsb.2020.02.012","article-title":"Targeting Human MutT Homolog 1 (MTH1) for Cancer Eradication: Current Progress and Perspectives","volume":"10","author":"Yin","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"150","DOI":"10.2337\/db07-0903","article-title":"MT1-MMP Expression in First-Trimester Placental Tissue Is Upregulated in Type 1 Diabetes as a Result of Elevated Insulin and Tumor Necrosis Factor-Alpha Levels","volume":"57","author":"Hiden","year":"2008","journal-title":"Diabetes"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nprot.2009.197","article-title":"Measurement of Superoxide Dismutase, Catalase and Glutathione Peroxidase in Cultured Cells and Tissue","volume":"5","author":"Weydert","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Mehta, S.K., Gowder, S.J.T., Mehta, S.K., and Gowder, S.J.T. (2015). Members of Antioxidant Machinery and Their Functions. Basic Principles and Clinical Significance of Oxidative Stress, IntechOpen.","DOI":"10.5772\/61884"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.2353\/ajpath.2007.070528","article-title":"Oxidative Stress, Gene Expression, and Protein Changes Induced in the Human Placenta during Labor","volume":"171","author":"Yung","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Novacescu, D., Latcu, S., Bardan, R., Daminescu, L., and Cumpanas, A. (2023). Contemporary Biomarkers for Renal Transplantation: A Narrative Overview. J. Pers. Med., 13.","DOI":"10.3390\/jpm13081216"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/9\/1074\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:43:57Z","timestamp":1760111037000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/9\/1074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,28]]},"references-count":88,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["life14091074"],"URL":"https:\/\/doi.org\/10.3390\/life14091074","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,28]]}}}