Iron overload in endometriosis peritoneal fluid induces early embryo ferroptosis mediated by HMOX1

Chen

et al. 2023

Preprint

Ferroptosis, a cohering network integrating iron, amino acids, lipids, and redox chemicals together，is a unique regulated cell death (RCD). Iron overload, excessive reactive oxygen species (ROS), and lipid peroxidation all contribute to the onset of ferroptosis. In recent years, a growing body of evidence suggests that ferroptosis is associated with some female reproductive diseases. The purpose of our review is to give a brief description of ferroptosis activation mechanism and relationship to female reproductive diseases including infertility, pregnancy associated diseases and ovarian cancer.

Section: The Two Sides Effects Of Ferroptosis In Emsmentioning

confidence: 99%

“…According to a study, HMOX1 is elevated during embryonic ferroptosis and inhibits it by maintaining mitochondrial activity and protect them from oxidative stress. 63 When considered collectively, we cannot ignore the impact of ferroptosis for the subsequent pathologic processes of EMs.…”

Section: The Two Sides Effects Of Ferroptosis In Emsmentioning

confidence: 99%

Ferroptosis in female reproductive diseases: from potential pathogenesis to therapy

Chen

et al. 2023

Preprint

“…Ferroptosis could be triggered during development or during normal homeostatic tissue turnover, by the accumulation of (1) iron [ 25 , 26 , 27 , 28 , 29 ] or (2) PUFAs [ 17 ], or by (3) the depletion of the antioxidant glutathione (GSH) [ 30 ], decreased function of glutathione peroxidase 4 (GPX4), which mediates the reduction of lipid peroxides [ 31 , 32 ], or the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [ 33 , 34 , 35 ].…”

Section: Ferroptosis and Mechanismsmentioning

confidence: 99%

Ferroptosis: A Potential Therapeutic Target in Acute Kidney Injury

Hosohata

Harnsirikarn

Chokesuwattanaskul

2022

IJMS

Ferroptosis is a recently recognized form of nonapoptotic cell death that is triggered by reactive oxidative species (ROS) due to iron overload, lipid peroxidation accumulation, or the inhibition of phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). Recent studies have reported that ferroptosis plays a vital role in the pathophysiological process of multiple systems such as the nervous, renal, and pulmonary systems. In particular, the kidney has higher rates of O2 consumption in its mitochondria than other organs; therefore, it is susceptible to imbalances between ROS and antioxidants. In ischemia/reperfusion (I/R) injury, which is damage caused by the restoring blood flow to ischemic tissues, the release of ROS and reactive nitrogen species is accelerated and contributes to subsequent inflammation and cell death, such as ferroptosis, as well as apoptosis and necrosis being induced. At the same time, I/R injury is one of the major causes of acute kidney injury (AKI), causing significant morbidity and mortality. This review highlights the current knowledge on the involvement of ferroptosis in AKI via oxidative stress.

“…Ferroptosis as an iron-dependent form of non-apoptotic cell death [ 6 ], and it is closely linked to endometriosis attributed to its high iron environment. A recent study reported that overloaded iron in endometriosis peritoneal fluid (PF) had harmful effects on the development of early embryos [ 7 ]. Our recent study has reported that follicular fluid (EMFF) with iron overload induces ferroptosis of granulosa cells and oocyte dysmaturity, and further contributes to EM-related infertility [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Baicalein Relieves Ferroptosis-Mediated Phagocytosis Inhibition of Macrophages in Ovarian Endometriosis

Liu

et al. 2022

CIMB

Iron overload and oxidative stress have been reported to contribute to ferroptosis in endometriotic lesions. However, the possible roles of iron overload on macrophages in endometriosis (EMs) remain unknown. Based on recent reports by single-cell sequencing data of endometriosis, here we found significant upregulations of ferroptosis-associated genes in the macrophage of the endometriotic lesion. Additionally, there was an elevated expression of HMOX1, FTH1, and FTL in macrophages of peritoneal fluid in EMs, as well as iron accumulation in the endometriotic lesions. Notably, cyst fluid significantly up-regulated levels of intracellular iron and ferroptosis in Phorbol-12-myristate-13-acetate (PMA)-stimulated THP-1 cells. Additionally, high iron-induced ferroptosis obviously reduced PMA-stimulated THP-1 cells’ phagocytosis and increased the expression of angiogenic cytokines, such as vascular endothelial growth factor A (VEGFA) and interleukin 8 (IL8). Baicalein, a potential anti-ferroptosis compound, increased GPX4 expression, significantly inhibited ferroptosis, and restored phagocytosis of THP-1 cells in vitro. Collectively, our study reveals that ferroptosis triggered by high iron in cyst fluid promotes the development of EMs by impairing macrophage phagocytosis and producing more angiogenic cytokines (e.g., IL8 and VEGFA). Baicalein displays the potential for the treatment of EMs, especially in patients with high ferroptosis and low phagocytosis of macrophages.