Exosomal miR‐27 negatively regulates ROS production and promotes granulosa cells apoptosis by targeting SPRY2 in OHSS

Abstract

Ovarian hyperstimulation syndrome (OHSS) is one of the most dangerous iatrogenic complications in controlled ovarian hyperstimulation (COH). The exact molecular mechanism that induces OHSS remains unclear. In recent years, accumulating evidence found that exosomal miRNAs participate in many diseases of reproductive system. However, the specific role of miRNAs, particularly the follicular fluid‐derived exosomal miRNAs in OHSS remains controversial. To identify differentially expressed follicular fluid exosomal miRNAs from OHSS and non‐OHSS patients, the analysis based on miRNA‐sequence was conducted. The levels of 291 miRNAs were significantly differed in exosomes from OHSS patients compared with normal control, and exosomal miR‐27 was one of the most significantly down‐regulated miRNAs in the OHSS group. By using MiR‐27 mimic, we found it could increase ROS stress and apoptosis by down‐regulating the expression of p‐ERK/Nrf2 pathway by negatively regulating SPRY2. These data demonstrate that exosomal miRNAs are differentially expressed in follicular fluid between patients with and without OHSS, and follicular fluid exosomal miR‐27 may involve in the pathological process of OHSS development.

Irradiated Cell-derived Exosomes Enhance Cell Proliferation and Radioresistanceviathe MAPK/Erk Pathway

“…Yang et al demonstrated that bladder cancer cell-derived exosomes inhibited the apoptosis of cancer cells, and these effects were triggered by the activation of the PI3K/Akt and MAPK/Erk pathways (19). Erk1/2 is a protein kinase expressed in a wide range of cell types and regulates cell proliferation, apoptosis, and treatment resistance (20)(21)(22). We hypothesized that an undefined factor was translocated from irradiated cells to other cells, resulting in enhanced cell proliferation via the ERK pathway.…”

The Varied Impacts of Vascular Endothelial Growth Factor-a (VEGF-a) on Vasculature in Ovarian Hyper Stimulation Syndrome (OHSS) and Obesity

“…In addition, some proinflammatory and vasoactive factors have directly or indirectly been involved in this process, resulting in shifting of intravascular fluid into extravascular compartment which is known as third space. The vasoactive factors include interleukin (IL)-1β, transforming growth factor (TGF)-α, TGF-β, endothelin-1, insulin-like growth factor 1 (IGF-1), epidermal growth factor (EGF), von Willebrand factor (VWF), prostaglandin, basic problast growth factor (BPGF), inhibin, prolactin, estrogen, histamine, serotonin, renin-angiotensin-aldosterone system, and most importantly, vascular endothelial growth factor (VEGF) [1,13,[21][22][23][24][25]. Among the factors mentioned above, a few of them are not strongly evidenced to approve themselves as key mediators for increasing vascular permeability in OHSS, despite of being supposed as possible factors for enhancing vascular permeability in the past [17].…”

Recent Advances in KEAP1/NRF2-Targeting Strategies by Phytochemical Antioxidants, Nanoparticles, and Biocompatible Scaffolds for the Treatment of Diabetic Cardiovascular Complications

“…Though NPs are often used as ROS inducers, as is the case in the treatment of cancer or bacterial infections, a growing number of studies report their successful application as ROS modulators in the treatment of diabetes and its cardiovascular complications (161,181). Indeed, as a rule of thumb NPs show a biphasic effect when it comes to ROS scavenging/stimulation effects (98,128). Whereas low concentrations of NPs trigger the activity of antioxidant enzymes such as catalase (CAT) and SOD, as it is desirable when dealing with diabetes and its complications, high concentrations of NPs can overwhelm such antioxidant systems, making a reliable and target-specific weapon for cancer treatment.…”

“…Whereas low concentrations of NPs trigger the activity of antioxidant enzymes such as catalase (CAT) and SOD, as it is desirable when dealing with diabetes and its complications, high concentrations of NPs can overwhelm such antioxidant systems, making a reliable and target-specific weapon for cancer treatment. This latter behavior comes as a result of (a) NPs accumulation to the target tissue through enhanced permeability and retention (EPR) and\or cancer environment-specific molecular targeting, and (b) NPs-triggered apoptosis of target cancer cells through mitochondrial membrane depolarization and consequent oxidation of key molecules in the electron transport chain such as NADPH and NADPH oxidase (48,98). Indeed, excessive NPs concentrations are associated with cytotoxicity in vitro (14,85) and neutrophils activation, which leads to an additional ROS production in vivo (98).…”

“…This latter behavior comes as a result of (a) NPs accumulation to the target tissue through enhanced permeability and retention (EPR) and\or cancer environment-specific molecular targeting, and (b) NPs-triggered apoptosis of target cancer cells through mitochondrial membrane depolarization and consequent oxidation of key molecules in the electron transport chain such as NADPH and NADPH oxidase (48,98). Indeed, excessive NPs concentrations are associated with cytotoxicity in vitro (14,85) and neutrophils activation, which leads to an additional ROS production in vivo (98). Physicochemical properties at the basis of such behaviors all reside in NPs surface to volume ratio, size, and chemical composition: a higher surface on volume ratio is associated with higher reactivity, while the chemical composition of the surface, as well as the electron density and distribution, determine the NP interactome (1).…”