Comprehensive overview of COVID-19-related respiratory failure: focus on cellular interactions.

The pandemic outbreak of coronavirus disease 2019 (COVID-19) has created health challenges in all parts of the world. Understanding the entry mechanism of this virus into host cells is essential for effective treatment of COVID-19 disease. This virus can bind to various cell surface molecules or receptors, such as angiotensin-converting enzyme 2 (ACE2), to gain cell entry. Respiratory failure and pulmonary edema are the most important causes of mortality from COVID-19 infections. Cytokines, especially proinflammatory cytokines, are the main mediators of these complications. For normal respiratory function, a healthy air-blood barrier and sufficient blood flow to the lungs are required. In this review, we first discuss airway epithelial cells, airway stem cells, and the expression of COVID-19 receptors in the airway epithelium. Then, we discuss the suggested molecular mechanisms of endothelial dysfunction and blood vessel damage in COVID-19. Coagulopathy can be caused by platelet activation leading to clots, which restrict blood flow to the lungs and lead to respiratory failure. Finally, we present an overview of the effects of immune and non-immune cells and cytokines in COVID-19-related respiratory failure.

Ovarian stimulation and exogenous progesterone affect the endometrial miR-16-5p, VEGF protein expression, and angiogenesis.

Angiogenesis, where vascular endothelial growth factor (VEGF) is critically involved, is an important factor in endometrial receptivity. Angio-miRNAs form a special class of microRNAs (miRNAs) that target angiogenic genes and regulate angiogenesis. Various studies have shown that ovarian stimulation and exogenous progesterone affect endometrial vascular density. The present research aimed to assess the impact of HMG/HCG and progesterone on miR-16-5p, VEGF protein expression, and angiogenesis in the mouse endometrium during the preimplantation period. Forty adult female mice were divided into four groups: 1) control, 2) ovarian stimulation (HMG and 48 h after HCG IP), 3) progesterone (progesterone IP for 3 days), 4) ovarian stimulation + progesterone (HMG and 48 h after HCG IP) + (progesterone IP for 3 days) groups.The mice were sacrificed 96 h following HCG administration. miR-16-5p, VEGF protein expression, and CD31-positive cell (Endothelial cell) density were specified.The results showed that endothelial cell density,VEGF protein, and miR-16-5p expression increased in all treatment groups, with the maximum increase belonging to the ovarian stimulation + progesterone group. This study provides evidence that ovarian stimulation and progesterone administration enhance endometrial angiogenesis through VEGF protein upregulation. Furthermore, except for miR-16-5p, other miRNAs and molecules appear to be involved in angiogenic pathways, thereby requiring further studies.

Expression and clinicopathological significance of lipin-1 in human breast cancer and its association with p53 tumor suppressor gene.

Breast cancer (BC) is an important cause of female cancer-related death. It has recently been demonstrated that metabolic disorders including lipid metabolism are a hallmark of cancer cells. Lipin-1 is an enzyme that displays phosphatidate phosphatase activity and regulates the rate-limiting step in the pathway of triglycerides and phospholipids synthesis. The objective of this study was to evaluate lipin-1 expression, its prognostic significance, and its correlation with p53 tumor suppressor in patients with BC. In this study, 55 pairs of fresh samples of BC and adjacent noncancerous tissue were used to analyze lipin-1, using quantitative real-time polymerase chain reaction and immunohistochemistry (IHC) staining. The expression of other clinicopathological variables and p53 was also examined using IHC technique. The cell migration was studied in MCF-7 and MDA-MB231 cells following the inhibition of lipin-1 by propranolol. Our results show that the relative expression of lipin-1 messenger RNA was significantly higher in BC tissues compared with the adjacent normal tissue and its inhibition reduced cell migration in cancer cells. This upregulation was negatively correlated with histological grade of tumor and p53 status (p = .001 and p = .034) respectively and positively correlated with the tumor size (p = .006). Our results also seem to indicate that the high lipin-1 expression is related to a good prognosis in patients with BC. The expression of lipin-1 may be considered as a novel independent prognostic factor. The inhibition of lipin-1 may also have therapeutic significance for patients with BC. The correlation between lipin-1 and p53 confirms the role of p53 in the regulation of lipid metabolism in cancer cells.

Epstein-Barr virus and thyroid cancer: The role of viral expressed proteins.

BACKGROUND: Thyroid cancer is a common endocrine malignancy whose incidence has increased in recent years. Several internal and external risk factors are involved in the development of this cancer, such as infectious agents. Evidence supporting the role of viral infection as an etiology for the invasiveness of thyroid cancer is increasing. The aim of this study was to determine the presence of the Epstein-Barr virus (EBV) and the association between viral gene products and thyroid tumor development. METHODS: Fifty-seven thyroid cancer specimens were collected from the same number of patients as well as 18 samples from healthy controls. The presence of the EBV genome and the genotyping was examined by polymerase chain reaction (PCR). Also, an enzyme-linked immunosorbent assay and real-time PCR were used to measure the expression levels of viral and cellular genes. RESULTS: The EBV DNA was detected in 71.9% of the samples, and it was also found that the presence of the EBV was associated with increasing development of thyroid tumor. CONCLUSION: Our results demonstrated that EBV infection may play a role in the development of thyroid tumor.

Endometrial pinopode biomarkers: Molecules and microRNAs.

Ultrastructural changes on the apical surface of the luminal epithelium of the uterus are known as pinopodes. Their morphology in species and in special species is associated with different results about size, duration, and percentage of surface area covered by pinopodes. The content of pinopodes is different in rodents and humans. In mice and rats pinopodes have many vacuoles and no organelle that extends to the actin stalk above the microvilli. Human pinopodes do not have a large vacuole and contain the golgi complex, a rough endoplasmic reticulum, secretory vesicles, and mitochondria that extend from the entire cell surface. It has been suggested that pinopodes are good markers of endometrial receptivity and implantation window. There are several molecular markers related to the presence of pinopodes, including integrins, leukemia inhibiting factor (LIF), l-selectin, HOXA10, glutaredoxin, glycodelinA, heparin-binding epidermal growth factor, mucins, and microRNAs (miRNAs). Multiple lines of evidence have indicated that miRNAs could affect the expression of LIF and pinopodes in the endometrium and these molecules play key roles in implantation window processes. Here, we have summarized the morphology and function of pinopodes. Moreover, we have highlighted several molecules in relation to pinopodes that could be used as biomarkers.

NLRP3 inflammasome: Its regulation and involvement in atherosclerosis.

Inflammasomes are intracellular complexes involved in the innate immunity that convert proIL-1ß and proIL-18 to mature forms and initiate pyroptosis via cleaving procaspase-1. The most well-known inflammasome is NLRP3. Several studies have indicated a decisive and important role of NLRP3 inflammasome, IL-1ß, IL-18, and pyroptosis in atherosclerosis. Modern hypotheses introduce atherosclerosis as an inflammatory/lipid-based disease and NLRP3 inflammasome has been considered as a link between lipid metabolism and inflammation because crystalline cholesterol and oxidized low-density lipoprotein (oxLDL) (two abundant components in atherosclerotic plaques) activate NLRP3 inflammasome. In addition, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and lysosome rupture, which are implicated in inflammasome activation, have been discussed as important events in atherosclerosis. In spite of these clues, some studies have reported that NLRP3 inflammasome has no significant effect in atherogenesis. Our review reveals that some molecules such as JNK-1 and ASK-1 (upstream regulators of inflammasome activation) can reduce atherosclerosis through inducing apoptosis in macrophages. Notably, NLRP3 inflammasome can also cause apoptosis in macrophages, suggesting that NLRP3 inflammasome may mediate JNK-induced apoptosis, and the apoptotic function of NLRP3 inflammasome may be a reason for the conflicting results reported. The present review shows that the role of NLRP3 in atherogenesis can be significant. Here, the molecular pathways of NLRP3 inflammasome activation and the implications of this activation in atherosclerosis are explained.

MicroRNA: A novel target of curcumin in cancer therapy.

Curcumin is known as a natural dietary polyphenol which is extracted from Curcuma longa L. It has been shown that curcumin has a variety of pharmacological effects such as antioxidant, anti-cancer, anti-inflammatory, and anti-microbial activities. Anti-cancer effects of curcumin are due to targeting of a wide range of cellular and molecular pathways involved in cancer pathogenesis including NF-kB, MAPK, PTEN, P53, and microRNAs (miRNA) network. Multiple lines of evidence have indicated that curcumin exerts its therapeutic effects via regulating miRNA expression (e.g., miR-1, miR-7, miR-9, miR-34a, miR-181, miR-21, and miR-19) which could lead to the regulation of underlying cellular and molecular pathways involved in cancer pathogenesis. Exosomes are one of the important classes of biological vehicles which could be released from various types of cells such as cancer cells and stem cells and could change the behavior of recipient cells. It has been shown that treatment of cancer cells with different dose of curcumin leads to the release of exosomes containing curcumin. These exosomes could induce anti-cancer properties in recipient cells and reduce tumor growth. Hence, exosomes containing curcumin could be applied as powerful tools for cancer treatment. Here, we highlighted various miRNAs which could be affected by curcumin in various types of cancer. Moreover, we highlight exosomes containing curcumin as suitable therapeutic tools in cancer therapy.

Micro-RNAs as critical regulators of matrix metalloproteinases in cancer.

Metastasis is known to be one of the important factors associated with cancer-related deaths worldwide. Several cellular and molecular targets are involved in the metastasis process. Among these targets, matrix metalloproteinases (MMPs) play central roles in promoting cancer metastasis. MMPs could contribute toward tumor growth, angiogenesis, migration, and invasion via degradation of the extracellular matrix and activation of pre-pro-growth factors. Therefore, identification of various cellular and molecular pathways that affect MMPs could contribute toward a better understanding of the metastatic pathways involved in various tumors. Micro-RNAs are important targets that could affect MMPs. Multiple lines of evidence have indicated that deregulation of various micro-RNAs, including miR-9, Let-7, miR-10b, and miR-15b, affects metastasis of tumor cells via targeting MMPs.

Diet and cancer prevention: Dietary compounds, dietary MicroRNAs, and dietary exosomes.

Cancer is one of main health public problems worldwide. Several factors are involved in beginning and development of cancer. Genetic and internal/external environmental factors can be as important agents that effect on emerging and development of several cancers. Diet and nutrition may be as one of important factors in prevention or treatment of various cancers. A large number studies indicated that suitable dietary patterns may help to cancer prevention or could inhibit development of tumor in cancer patients. Moreover, a large numbers studies indicated that a variety of dietary compounds such as curcumin, green tea, folat, selenium, and soy isoflavones show a wide range anti-cancer properties. It has been showed that these compounds via targeting a sequence of cellular and molecular pathways could be used as suitable options for cancer chemoprevention and cancer therapy. Recently, dietary microRNAs and exosomes have been emerged as attractive players in cancer prevention and cancer therapy. These molecules could change behavior of cancer cells via targeting various cellular and molecular pathways involved in cancer pathogenesis. Hence, the utilization of dietary compounds which are associated with powerful molecules such as microRNAs and exosomes and put them in dietary patterns could contribute to prevention or treatment of various cancers. Here, we summarized various studies that assessed effect of dietary patterns on cancer prevention shortly. Moreover, we highlighted the utilization of dietary compounds, dietary microRNAs, and dietary exosomes and their cellular and molecular pathways in cancer chemoprevention.

Anti-Atherosclerotic Effects of Vitamins D and E in Suppression of Atherogenesis.

Atherosclerosis is a progressive and multifactorial disease which occurs under the influence of various risk factors including endothelial dysfunction (ED), oxidative stress, and low-density lipoprotein (LDL) oxidation. In contract to the initial hypotheses on the usefulness of vitamin E supplementation for cardiovascular disease prevention, large outcome trials showed consumption of vitamin E has no obvious effect on cardiovascular disease and, in some cases, it may even increase the rate of mortality. This seemingly unexpected finding may be due to the opposite effects of vitamin E compounds. Vitamin E is a group of compounds which have different and even opposing effects, yet in most of the studies, the exact consumed component of vitamin E is not determined. It appears that the combined consumption of gamma-tocopherol, vitamin C, D, and tetrahydrobiopterin (BH4) may be extremely effective in both preventing atherogenesis and suppressing plaque development. In this regard, one of main issues is effect of vitamins E and D deficiency on microRNAs network in atherosclerosis. Various studies have indicated that miRNAs have key roles in atherosclerosis pathogenesis. The deficiency of vitamins E and D could provide a deregulation for miRNAs network and these events could lead to progression of atherosclerosis. Here, we highlighted a variety of mechanisms involve in the progression of atherosclerosis and effects of vitamins D and E on these mechanisms. Moreover, we summarized miRNAs involve in atherosclerosis and their regulation by vitamins E and D deficiency. J. Cell. Physiol. 232: 2968-2976, 2017. © 2016 Wiley Periodicals, Inc.

Implantation Window and Angiogenesis.

In recent decades, infertility is one of the health problems worldwide. One of the most crucial events in reproductive period is implantation window (IW). In the time after IW period, the embryo cannot connect to the endometrium; therefore the most critical issue for successful implantation is timely entrance of embryo to the uterine cavity during the IW. Implantation failure is responsible for many cases of infertility and is the most important limiting factor for achieving a successful outcome using the assisted reproductive techniques (ART). The aim of this study was to investigate the receptivity of the endometrium and factors affecting it with emphasizing on the role of angiogenesis. Interaction between the embryo and the endometrium is affected by molecular interactions among cytokines, growth factors, hormones, and cell adhesion molecules, causing endometrial receptivity. Also, angiogenesis is a process that has an important role in human implantation. Estrogen and progesterone hormones are two important regulation keys in angiogenesis and implantation process. It is expected that effective and stimulating drugs of angiogenesis can improve the characteristics of endometrial receptivity and prevent implantation failure in ART. It is hoped that with recent advances in the field of molecular medicine, improvement of angiogenesis in human endometrium and prevention of the implantation failure be achieved. Here, we summarized various factors could affect on endometrial receptivity and the role of them on angiogenesis. J. Cell. Biochem. 118: 4141-4151, 2017. © 2017 Wiley Periodicals, Inc.

Erythropoietin improves spatial learning and memory in streptozotocin model of dementia.

Alzheimer's disease is associated to impairments of learning and memory. Because studies demonstrated that erythropoietin has positive effects on central nervous system, the aim of this study was to evaluate the effect of erythropoietin on spatial learning and memory in a well defined model for Alzheimer's disease. Rat model of Alzheimer's was created by injecting streptozotocin in lateral ventricles of the brain. Two weeks later, the rats were assessed through passive avoidance learning test to confirm the induction of Alzheimer's. After that, they received erythropoietin (5000IU/kg) every other day, for two weeks and then spatial learning and memory were assessed by a 5-day protocol of Morris water maze test in them. The results showed that streptozotocin severely damaged learning and memory in rats. Erythropoietin had no significant effect in the control rats; however, it significantly improved learning and memory in rats with Alzheimer's disease, as the task performance of the rats treated with erythropoietin was like the control group. The results suggest that erythropoietin can be considered as an effective treatment for neurodegenerative damages.

Ghrelin does not modulate angiogenesis in matrigel plug in normal and diet-induced obese mice.

BACKGROUND: The reciprocal interaction between adipocytes and angiogenesis is considered as an essential component in the development and expansion of adipose tissue. The aim of this study was to evaluate the effect of ghrelin on angiogenic response using in vivo angiogenesis assay of matrigel plug and its correlation with serum leptin levels in normal and diet-induced obese mice. MATERIALS AND METHODS: This experimental study has been done on 24 male C57BL/6 mice which were randomly divided into four groups: Normal diet (ND) or control, ND + ghrelin, high-fat-diet (HFD) or obese and HFD + ghrelin (n = 6/group). Obese and control groups received HFD or standard diet for 14 weeks. Then, growth factor reduced matrigel plug (500 µl) containing bFGF (basic fibroblast growth factor; 100 ng) with or without ghrelin (100 µg/kg) was injected subcutaneously in the mid-ventral abdominal region of each mice. After 10 days, blood samples were taken and matrigel plugs were removed under anesthesia and angiogenic response was assessed by immunohisochemical staining. RESULTS: HFD significantly increased angiogenesis in matrigel plug as expressed as the number of CD31-positive cells than standard diet (43 ± 5 vs. 13 ± 2.5 CD31(+) cells/field). Ghrelin did not alter angiogenesis in matrigel plug in both obese and control groups. There was a strong positive correlation between the number of CD31-positive cells and serum leptin concentration (r = 0.91). CONCLUSION: Leptin as an angiogenic factor has a positive correlation with angiogenesis in matrigel plug model of angiogenesis and ghrelin could not alter angiogenesis.

The preventive effect of Zingiber officinale essential oil on demyelination of corpus callosum in a cuprizone rat model of multiple sclerosis.

Objective: Multiple sclerosis (MS) is the most prevalent neurological disability among young adults. Anti-inflammatory drugs have shown to be effective in MS. The anti-inflammatory and antioxidative properties of Zingiber officinale (ginger) have been shown and proven in many phytotherapy studies. This study aimed to evaluate effects of ginger essential oil on preventing myelin degradation in a rat model of MS. Materials and Methods: In this study, we divided 49 rats into 7 groups; 4 control and 3 experimental groups that received 3 different dose of ginger essential oil (50, 100, and 150 mg/kg/day) for treatment of cuprizone-induced demyelinated rats. Basket test and transmission electron microscopy were performed in this study. Olig2 and Mbp genes and proteins were respectively evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Results: Histologically, cuprizone created demyelination in the corpus callosum fibers. Remyelination of fibers was seen in the group treated with the medium dose of ginger essence, by toluidine blue staining. transmission electron microscopy (TEM) revealed increased thickness of the myelin of fibers in all 3 treated groups (p<0.05). Feeding by the medium dose of ginger essence significantly increased the levels of Mbp and Olig2 genes (p<0.05). ELISA test showed that 100 mg/kg/day of ginger caused a significant difference between experimental and the cuprizone-induced groups (p<0.05). Conclusion: Our findings suggested that administration of ginger essential oil prevented demyelination and improved remyelination of rats` corpus callusom and can be used as an effective substance in the prevention of MS.

Effect of Vitamin E on Apoptosis of the Endothelial Cells of the Carotid Arteries in Hypercholesterolemic Male Rabbits.

INTRODUCTION: Cardiovascular disease is the principal cause of mortality and morbidity in developed countries, leading to the formation of atherosclerosis plaques and thrombosis. Apoptosis of endothelial cells is one of the primary factors in vascular thrombosis. Lipids, when oxidized by endothelial cells, result in an increased thickness of the arterial wall. Iron is also recognized as an atherogenic element that induces atherosclerosis. There remains uncertainty about the antioxidative role of vitamin E in the formation of atherosclerosis. In this study, the authors evaluated the effect of iron and vitamin E on the apoptosis of endothelial cells in the carotid arteries of hypercholesterolemic male rabbits. METHOD: Thirty white male rabbits were randomly divided into five groups and fed the following diet for six weeks: Group 1: control, Group 2: cholesterol (1%), Group 3: cholesterol (1%) + vitamin E (50 mg/kg), Group 4: cholesterol (1%) + Iron (50 mg/kg), and Group 5: cholesterol (1%) + vitamin E (50 mg/kg) + Iron (50 mg/kg). Serum cholesterol, TG, HDL, and LDL levels were assessed after six weeks. Finally, the animals were sacrificed with ketamine, and carotid arteries were removed. The samples were fixed in 10% formalin, and TUNEL staining was used after the tissue processing. Cell counts were carried out under a light microscope. RESULTS: Vitamin E decreased Serum cholesterol and apoptotic endothelial cells in the hypercholesterolemic + vitamin E diet (P< 0.05). However, they increased significantly in the interference groups compared to the control group (P< 0.05). CONCLUSION: According to our findings, vitamin E showed to have a beneficial effect on preventing cardiovascular diseases and may play a positive role in the prevention of atherosclerosis.

Protective effect of soy protein on collagen-induced arthritis in rat.

To evaluate preventive and therapeutic effects of soy protein on collagen-induced arthritis rats. Sprague-Dawley rats immunized with bovine type II collagen emulsified in adjuvant and treated with soy protein (7 g/kg), dexamethasone (1 mg/kg), and casein (in control groups) by daily gavages feedings for 30 days. Score of arthritis recorded every day for each paws of animal. Tumor necrosis factor-alpha, interleukin6, leptin, and adiponectin were measured in serums. Treatment with soy protein resulted in significant delay in time to onset of arthritis as well as significantly decreased arthritis incidence, clinical arthritis severity score, histopathological arthritis severity score, and in vivo cell-mediated immunity to collagen (P < 0.05). Administration of soy protein significantly suppressed the progression of collagen II-induced arthritis and inhibited the production of tumor necrosis factor-alpha, interleukin6, leptin, and adiponectin. Soy protein appeared to be a potent immunomodulatory inhibitor of collagen II-induced arthritis in rats. It could delay onset of RA and reduced cartilage erosion and synovitis inflammation. Therefore, it may be a useful protein in the prevention and treatment of rheumatoid arthritis patient.

Role of fenofibrate in restoring angiogenesis in diabetic and control hind limb ischemic rats.

In this study, we examined the effect of fenofibrate, an agonist of peroxisome proliferator-activated receptor α (PPARα), on angiogenesis and serum nitric oxide (NO), vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) in diabetic and control hind limb ischemic rats. Male Wistar rats underwent left hind limb ischemia. The experimental groups consisted of rats: control, diabetic, control receiving fenofibrate (100 mg/kg/day, by gavage) and diabetic receiving fenofibrate. After 21 days, blood samples were taken and capillary density and capillary/fiber ratio of the ischemic hind limb muscle was evaluated by immunohistochemistry. Activation of PPARα by fenofibrate restored neovascularization in diabetic and control hind limb ischemic rats (p < 0.05). Fenofibrate administration significantly increased serum nitrite concentration, the main metabolite of NO, without significant changes in serum VEGF and VEGFR-2 concentrations. It seems that fenofibrate enhances angiogenesis in hind limb ischemia possibly through increasing of NO bioavailability and can be considered for treatment of diabetic peripheral vascular diseases in future human studies.

The effect of Zingiber Officinale Extract on Preventing Demyelination of Corpus Callosum in a Rat Model of Multiple Sclerosis

Background: Multiple sclerosis (MS) is the most prevalent neurological disability of young adults. Anti-inflammatory drugs have relative effects on MS. The anti-inflammatory and antioxidative effects of Zingiber officinale (ginger) have been proven in some experimental and clinical investigations. The aim of this study was to evaluate the effects of ginger extract on preventing myelin degradation in a rat model of MS. Methods: Forty nine male Wistar rats were used in this study and divided into four control groups: the normal group, cuprizone-induced group, sham group (cuprizone [CPZ] + sodium carboxymethyl cellulose [NaCMC]), standard control group (fingolimod + cuprizone), including three experimental groups of CPZ, each receiving three different doses of ginger extract: 150, 300, and 600mg/kg /kg/day. Results: Ginger extract of 600 mg/kg prevented corpus callosum from demyelination; however, a significant difference was observed in the fingolimod group (p < 0.05). Difference in the CPZ group was quite significant (p < 0.05). Conclusion: Treatment with ginger inhibited demyelination and alleviated remyelination of corpus callosum in rats. Therefore, it could serve as a therapeutic agent in the MS.

Cytokines and microRNAs in SARS-CoV-2: What do we know?

The coronavirus disease 2019 (COVID-19) pandemic constitutes a global health emergency. Currently, there are no completely effective therapeutic medications for the management of this outbreak. The cytokine storm is a hyperinflammatory medical condition due to excessive and uncontrolled release of pro-inflammatory cytokines in patients suffering from severe COVID-19, leading to the development of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS) and even mortality. Understanding the pathophysiology of COVID-19 can be helpful for the treatment of patients. Evidence suggests that the levels of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1 and IL-6 are dramatically different between mild and severe patients, so they may be important contributors to the cytokine storm. Several serum markers can be predictors for the cytokine storm. This review discusses the cytokines involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, focusing on interferons (IFNs) and ILs, and whether they can be used in COVID-19 treatment. Moreover, we highlight several microRNAs that are involved in these cytokines and their role in the cytokine storm caused by COVID-19.

Evaluating the effect of ovarian stimulation and exogenous progesterone on CD31-positive cell density, VEGF protein, and miR-17-5p expression of endometrium immediately before implantation.

BACKGROUND: MicroRNAs (miRNAs) form a special class of RNAs regulating endometrial functions like cell proliferation, differentiation, angiogenesis, and blastocyst implantation. In addition to providing suitable conditions for embryo development, angiogenesis is a prerequisite to natural pregnancy. The family of vascular endothelial growth factor (VEGF) and its receptors are the main physiological and pathological angiogenesis regulators in the endometrium. In the past, research has demonstrated alteration of angiogenesis and subsequent endometrial receptivity in the stimulated and luteal phase support cycles, when compared with natural cycles. OBJECTIVE: The objective of this study is to investigate the effect of ovarian stimulation and exogenous progesterone on the density of CD31-positive cell (Endothelial cell), VEGF protein, and miR-17-5p expression in the mouse endometrium immediately before implantation. METHODS: We employed ovarian stimulated and luteal phase support mice models induced by HMG/HCG and progesterone. The endometrial CD31-positive cell density was determined by immunohistochemistry (IHC) staining, the level of VEGF protein by IHC and western blot analysis, and finally the miR-17-5p expression was determined by the real-time PCR method. RESULTS: The density of endothelial cell, VEGF protein, and miR-17-5p expression increased in all of the experimental mice when compared to the control group, with the maximum increase having been seen in the group that had received progesterone after ovarian stimulation. CONCLUSION: This research indicates that ovarian stimulation and exogenous progesterone lead to an increase in the number of endothelial cells by upregulating the VEGF protein. Moreover, except for miR-17-5p, other microRNAs and molecules are presumably involved in angiogenic pathways, thereby requiring more studies.