Antioxidant Defenses, Oxidative Stress Responses, and Apoptosis Modulation in Spontaneous Abortion: An Immunohistochemistry Analysis of First-Trimester Chorionic Villi
Author:
Vornic Ioana12, Nesiu Alexandru3, Ardelean Ana Maria12, Todut Oana Cristina12, Pasare Victoria Cristina12, Onel Cristina12, Raducan Ionuț Daniel1, Furau Cristian George2ORCID
Affiliation:
1. Doctoral School, Faculty of Medicine, “Vasile Goldiș” Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania 2. Discipline of Gynecology, Faculty of Medicine, “Vasile Goldiș” Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania 3. Discipline of Urology, Faculty of Medicine, “Vasile Goldiș” Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania
Abstract
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—glutathione (GSH), MutT Homolog 1 (MTH1), and apoptotic regulation modulators—tumor 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.
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