Autophagy and its Regulation in Diabetic Embryopathy

SARS-CoV-2感染诱导胎盘铁性下垂的激活 摘要 怀孕是感染SARS-CoV-2和更糟糕的新冠肺炎结局的风险因素。因此，有一个 迫切需要研究导致不良妊娠发病的潜在机制 妊娠期最佳新冠肺炎治疗的结果和发展。最不利的妊娠 结果源于胎盘，因为人类胎盘可以合成许多激素和细胞因子来 影响卵巢、子宫、乳腺和胎儿生理。细胞死亡研究的最新进展 细胞死亡机制中的机制使人们显著地认识到铁性下垂在调节 细胞的命运。作为非凋亡性程序性细胞死亡的一种形式，铁下垂的特征是氧化还原活性铁. 含多不饱和脂肪酸的磷脂和受损脂质的依赖羟基过氧化 过氧化修复能力。因为铁代谢失调的作用已被证明在 在新冠肺炎病因学中的重要作用，本研究的中心假设是SARS-CoV-2感染 导致胎盘中铁下垂过程的激活，从而起到关键的作用 胎盘功能失调和随后不良妊娠结局的发病机制。 我们计划追求两个目标。目的1.确定铁性上睑下垂的基因表达水平。 SARS-CoV-2感染人原代胎盘组织和滋养层细胞。一些研究表明， 在经历产科并发症的孕妇中，新冠肺炎的风险增加。虽然有多个 潜在的信号通路可能将这两个事件联系在一起，我们假设铁下垂主要是 负责任。目的2.重述SARS-CoV-2感染诱导的铁性下垂过程的激活 在体外的胎盘中。我们将使用人原代胎盘细胞滋养层细胞作为体外模型来完成 这个目标。这项研究具有重要意义，因为它解决了一个关于机理的基本问题 新冠肺炎与不良临床结局发病机制的潜在相关性。此外，这项研究还 探索了一个新的概念：铁下垂信号可以作为这样一种机制，从而促进 治疗这些并发症的新的有效的治疗方法。

SARS-CoV-2 infection induces activation of ferroptosis in the placenta Summary Pregnancy is a risk factor for SARS-CoV-2 infection and worse COVID-19 outcomes. Therefore, there is an urgent need for research into underlying mechanisms leading to the pathogenesis of adverse pregnancy outcomes and the development of optimal COVID-19 treatment during pregnancy. Most adverse pregnancy outcomes are of placental origin because the human placenta can synthesize many hormones and cytokines to influence ovarian, uterine, mammary, and fetal physiology. Recent advances in understanding cell death mechanisms in cell death mechanisms have led to significant recognition of the role of ferroptosis in regulating cell fate. As a form of nonapoptotic programmed cell death, ferroptosis is characterized by redox-active iron- dependent hydroxy-peroxidation of polyunsaturated fatty acid-containing phospholipids and compromised lipid peroxidation repair capacity. Because dysregulation of iron metabolism plays has been shown to play an important role in the etiology of COVID-19, the central hypothesis of this study is that SARS-CoV-2 infection leads to activation of the ferroptosis process in the placenta, thereby serving as a pivotal contributor to dysregulation of placental function and subsequently pathogenesis of adverse pregnancy outcomes. We plan to pursue two Aims. Aim 1. To determine gene expression levels of hallmarks of ferroptosis in SARS-CoV-2-infected human primary placental tissues and trophoblastic cells. A number of studies have shown increased COVID-19 risk among pregnant women experiencing obstetrical complications. While multiple underlying signaling pathways may associate these two events, we hypothesize that ferroptosis is primarily responsible. Aim 2. To recapitulate SARS-CoV-2 infection-induced activation of the ferroptosis process in the placenta in vitro. We will use human primary placental cytotrophoblast as an in vitro model to accomplish this Aim. This research is significant because it addresses a fundamental question regarding mechanisms underlying correlation of COVID-19 and pathogenesis of adverse clinical outcomes. Furthermore, this study explores a novel concept: ferroptosis signaling can serve as such a mechanism, thus facilitating development of new and effective therapeutic approaches for treatment of these complications.