{"id":453,"title":"Redox Imbalance and Antioxidant Defense in Fetal Growth Restriction (FGR): Pathophysiological Mechanisms, Biomarkers, and Therapeutic Perspectives","title_zh":"胎儿生长受限中的氧化还原失衡与抗氧化防御：病理生理机制、生物标志物与治疗前景","url":"https://doi.org/10.20944/preprints202610.3106.v1","doi":"10.20944/preprints202610.3106.v1","pmid":null,"journal":"Preprints.org","kind":"preprint","lang":"en","published_at":"2026-10-30T00:00:00+00:00","fetched_at":"2026-11-08T03:44:14+00:00","authors":["Varra F","Varras M","Varra V","Theodosis-Nobelos P","Stefanidis K","Philippou A"],"primary_topic":"endometrium","topics":[{"slug":"endometrium","score":4.0,"hits":["placenta","placental","placentation","trophoblast"]},{"slug":"ai-compute","score":2.0,"hits":["artificial intelligence","machine learning"]},{"slug":"embryology-lab","score":1.0,"hits":["microfluidic"]},{"slug":"repro-aging","score":1.0,"hits":["mitochondrial"]},{"slug":"omics-methods","score":1.0,"hits":["multi-omics"]}],"topic_score":4.0,"preference_score":10.0,"preference_labels":["多组学整合分析（任意生殖对象）"],"llm_score":66.0,"final_score":76.0,"score_dims":{"novelty":66,"rigor":40,"impact":58,"relevance":55,"translation":55},"recommend_reason":"综述覆盖面广，把铁死亡、还原应激悖论与AI+多组学风险分层串联起来，对胎盘源性与围产期研究有参考价值；但属预印本叙述性综述、缺乏系统检索与原始数据，且与ART实验室操作直接关联有限，宜作背景阅读。","keywords":["胎儿生长受限","胎盘氧化还原失衡","铁死亡","还原应激","多组学整合","生物标志物"],"selected":1,"story_id":263,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"europepmc-preprints","source_name":"Europe PMC · 预印本（领域内）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"preprints-org","journal_tier":"standard","journal_if":null,"is_mock":false,"summary_zh":"本文为叙述性综述，聚焦胎儿生长受限（FGR）中胎盘氧化还原稳态失衡。作者指出活性氧过量产生与抗氧化防御不足共同导致脂质、蛋白和DNA损伤，损害滋养细胞功能、血管重塑与营养转运；并整合铁死亡、内质网应激及非编码RNA介导的“redox-miR”氧化还原—表观遗传交互等新机制。文章还讨论了系统性抗氧化治疗的转化失败与“还原应激”悖论，评估多组学整合与AI机器学习（母血清氧化还原标志物联合胎儿多普勒指标）用于早期风险分层的潜力，并展望胎盘靶向纳米药物、胎盘芯片/类器官与自体线粒体移植等前沿方向。原文未提供原始数据。","summary":"Fetal growth restriction (FGR) is a major obstetric complication associated with increased perinatal morbidity, mortality, and adverse long-term metabolic outcomes in adulthood. Placental dysfunction stands as the principal driver in a substantial proportion of cases, with accumulating evidence indicating that the disruption of placental redox homeostasis plays a central role in its pathophysiology. This review provides a comprehensive synthesis of redox dysregulation in FGR, extending beyond classical oxidative injury to incorporate emerging non-linear paradigms. Excessive production of reactive oxygen species (ROS), coupled with inadequate antioxidant defenses, promotes lipid, protein, and DNA damage, thereby impairing trophoblast function, vascular remodeling, cell survival, and nutrient transport. Crucially, this review integrates recent breakthroughs in the fields of iron-dependent ferroptosis, endoplasmic reticulum stress, and complex redox-epigenetic cross-talk mediated by non-coding RNAs (\"redox-miRs\"). Furthermore, we address the translational failure of conventional systemic antioxidant therapies, highlighting the newly recognized paradox of reductive stress, where over-supplementation disrupts essential ROS-dependent signaling cascades during early placentation. To resolve these diagnostic and therapeutic limitations, this work evaluates the clinical utility of multi-omics integration for mapping placental metabolic reprogramming and artificial intelligence (AI) machine learning models that combine maternal serum redox biomarkers with longitudinal fetal Doppler metrics for early risk stratification. Finally, we explore next-generation obstetric frontiers, including placenta-targeted nanomedicine for localized drug delivery, Placenta-on-a-Chip microfluidic and organoid screening platforms, and autologous mitochondrial transplantation aimed at rescuing syncytiotrophoblast bioenergetics. Overall, current evidence underscores placental redox dysregulation as an interconnected, systemic failure rather than an isolated molecular defect. Moving toward precision, redox-guided perinatal management requires longitudinal human studies and well-designed clinical trials to validate whether the targeted restoration of redox homeostasis can translate into improved maternal, fetal, and neonatal outcomes.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}