Vornic Ioana, Nesiu Alexandru, Ardelean Ana Maria, Todut Oana Cristina, Pasare Victoria Cristina, Onel Cristina, Raducan Ionuț Daniel, Furau Cristian George
Doctoral School, Faculty of Medicine, "Vasile Goldiș" Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania.
Discipline of Gynecology, Faculty of Medicine, "Vasile Goldiș" Western University of Arad, Liviu Rebreanu Street, No. 86, 310414 Arad, Romania.
Life (Basel). 2024 Aug 28;14(9):1074. doi: 10.3390/life14091074.
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.
氧化应激（OS）和细胞凋亡是胎盘发育和功能的关键因素。它们之间的相互作用影响滋养层细胞的增殖、分化和侵袭，以及血管发育。这些过程之间的失衡会导致与妊娠相关的疾病，如先兆子痫、宫内生长受限，甚至自然流产。我们的研究旨在阐明预防性抗氧化/保护性OS反应因子——谷胱甘肽（GSH）、MutT同源蛋白1（MTH1），以及细胞凋亡调节因子——肿瘤蛋白p53和B细胞淋巴瘤（Bcl-2）转录本之间的关联，研究对象为自然流产（30例样本）与人工流产（20例样本），采用免疫组织化学（IHC）方法确定它们在流产胎儿胎盘组织样本中绒毛膜绒毛的蛋白质组表达。在此，比较统计分析显示，与人工流产相比，自然流产病例中OS反应因子GSH和MTH1均显著低表达。相反，对于细胞凋亡调节因子，p53在自然流产病例中的表达显著更高，而Bcl-2在自然流产病例中的表达显著更低。这些发现表明，与人工流产对照相比，自然流产样本中存在强烈的促细胞凋亡信号，同时抗细胞凋亡保护作用减弱、抗氧化防御能力耗尽以及氧化DNA损伤预防/修复受损。在此，我们关于OS和细胞凋亡是导致胎盘功能障碍和自然流产的紧密相关过程的假设似乎得到了证实。我们的结果进一步强调了维持氧化还原稳态和细胞凋亡调节对成功妊娠的重要性。了解这种相互作用的潜在机制对于开发管理OS、促进胎盘形成和避免不必要的细胞凋亡的潜在疗法至关重要，最终改善妊娠结局。补充抗氧化剂、调节p53活性以及增强DNA修复机制可能是减轻胎盘中OS和细胞凋亡的潜在方法。需要进一步研究来探索这些策略及其预防自然流产的功效。
