scholarly journals Molecular Predictors of Effective Implantation and Live Birth in IVF Programs

2021 ◽  
Vol 11 (4) ◽  
pp. 532-537
Author(s):  
Elena Chukhnina ◽  
Evgeny Kazachkov ◽  
Ekaterina Voropaeva ◽  
Ella Kazachkova ◽  
Miroslava Polina ◽  
...  
Keyword(s):  
Live Birth ◽  
Stromal Cells ◽  
Reproductive Age ◽  
Prognostic Models ◽  
Immunohistochemical Method ◽  
Morphological Examination ◽  
Endometrial Stromal Cells ◽  
Art Programs ◽  
Vitamin D Receptors ◽  
Blastocyst Implantation

The aim of the study was to improve the possibilities of predicting blastocyst implantation and live birth of ART programs in women of late reproductive age with tubal-peritoneal infertility based on immunohistochemical markers of the endometrium. Methods and Results: The results of IVF and IVF/ICSI programs were analyzed in 68 patients of late reproductive age (36-44 years of age) with tubal-peritoneal factor of infertility. Morphological examination of the endometrium was performed on Day 7 after confirmed ovulation in the cycle preceding ART. The expression of vitamin D receptors (VDR) and HOXA11 in endometrial stromal cells was assessed by immunohistochemical method. The effectiveness of using the endometrial markers VDR and HOXA11 as potential predictors of ART programs efficiency was confirmed by prognostic models. The levels of the stromal expression of VDR<8.7% and HOXA11<6.1% (probability >0.27) were determined to be favorable for successful blastocyst implantation. The expression levels of VDR<8.3% and HOXA11<6.1% in endometrial stromal cells are prognostically favorable for live birth (probability >0.19) in women of late reproductive age with tubal-peritoneal infertility who undergoing ART treatment with their own oocytes.

scholarly journals Lipidomic Alterations and PPARα Activation Induced by Resveratrol Lead to Reduction in Lesion Size in Endometriosis Models

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Zhengyun Chen ◽  
Chunyan Wang ◽  
Cuicui Lin ◽  
Lifeng Zhang ◽  
Huimei Zheng ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Therapeutic Potential ◽  
Lesion Size ◽  
Chronic Inflammatory Disease ◽  
Reproductive Age ◽  
Valuable Insight ◽  
Endometrial Stromal Cells ◽  
Proliferation Capacity ◽  
Significant Efficacy ◽  
Insight Into

Endometriosis is an estrogen-dependent chronic inflammatory disease that affects approximately 10% of women of reproductive age and up to 50% of women with infertility. The heterogeneity of the disease makes accurate diagnosis and treatment a clinical challenge. In this study, we generated two models of endometriosis: the first in rats and the second using human ectopic endometrial stromal cells (HEcESCs) derived from the lesion tissues of endometriosis patients. We then applied resveratrol to assess its therapeutic potential. Resveratrol intervention had significant efficacy to attenuate lesion size and to rectify aberrant lipid profiles of model rats. Lipidomic analysis revealed significant lipidomic alterations, including notable increases of sphingolipids and decreases of both glycerolipids and most phospholipids. Upon resveratrol application, both proliferation capacity and invasiveness parameters decreased, and the early apoptosis proportion increased for HEcESCs. The activation of PPARα was also noted as a factor potentially contributing to recovery from endometriosis in both models. Our study provides valuable insight into the mechanisms of resveratrol in endometriosis and therefore strengthens the potential for optimizing resveratrol treatment for this disease.

Effectiveness of programs of auxiliary reproductive technologies in patients of late reproductive age

GYNECOLOGY ◽  
2018 ◽  
Vol 20 (1) ◽  
pp. 109-112 ◽  
Author(s):  
E P Beik ◽  
A G Syrkasheva ◽  
N V Dolgushina
Keyword(s):  
Live Birth ◽  
Assisted Reproductive Technologies ◽  
Laboratory Data ◽  
Age Groups ◽  
Reproductive Technologies ◽  
Reproductive Age ◽  
Art Programs ◽  
Group 2 ◽  
Twofold Decrease ◽  
Group 1

The aim of the study was to study the effectiveness of assisted reproductive technologies (ART) programs in patients of different age groups, taking into account clinical and laboratory data. Materials and methods. A prospective cohort study included 188 patients with infertility of various genesis who were stratified according to age: group 1 (n=87) - patients of late reproductive age - LRA (>35 years), group 2 (n=101) - patients of early reproductive age (≤35 years). Results. In patients with ART compared with patients with LRA, the chances of pregnancy were reduced by 2.2 times (odds ratio - OR 2.2, 95% confidence interval - CI 1.1-4.3), the chances of live birth were 2 times (OR 2.0; 95% CI 1.0-3.9). The only factor affecting the onset of pregnancy in addition to age was the number of embryos received. The threshold age at which and above which the chances of pregnancy and live birth decreased as much as possible were the age of 37 years: the OR of pregnancy 2.6 (95% CI 1.4-5.1, AUC 61.3%), OR live birth 2.6 (95% CI 1.3-5.1, AUC 60.8%). Conclusions. In patients of LRA there is a twofold decrease in the effectiveness of ART programs due to a significant decrease in the number of oocytes obtained, mature oocytes, and, accordingly, embryos.

scholarly journals Dehydroepiandrosterone Inhibits Glucose Flux Through the Pentose Phosphate Pathway in Human and Mouse Endometrial Stromal Cells, Preventing Decidualization and Implantation

2011 ◽  
Vol 25 (8) ◽  
pp. 1444-1455 ◽  
Author(s):  
Antonina I. Frolova ◽  
Kathleen O'Neill ◽  
Kelle H. Moley
Keyword(s):  
Stromal Cells ◽  
Pentose Phosphate Pathway ◽  
Glucose Transporter ◽  
Polycystic Ovary ◽  
Pentose Phosphate ◽  
Reproductive Age ◽  
Endometrial Stromal Cells ◽  
Glucose Transporter 1 ◽  
Decidual Cells

Endometrial stromal cells (ESC) must undergo a hormone-driven differentiation to form decidual cells as a requirement of proper embryo implantation. Recent studies from our laboratory have demonstrated that decidualizing cells require glucose transporter 1 expression and an increase in glucose use to complete this step. The present study focuses on the glucose-dependent molecular and metabolic pathways, which are required by ESC for decidualization. Inhibition of glycolysis had no effect on decidualization. However, blockade of the pentose phosphate pathway (PPP) with pharmacologic inhibitors 6-aminonicotinamide or dehydroepiandrosterone (DHEA), and short hairpin RNA-mediated knockdown of glucose-6-phosphate dehydrogenase, the rate-limiting step in the PPP, both led to strong decreases in decidual marker expression in vitro and decreased decidualization in vivo. Additionally, the studies demonstrate that inhibition is due, at least in part, to ribose-5-phosphate depletion, because exogenous nucleoside administration restored decidualization in these cells. The finding that PPP inhibition prevents decidualization of ESC is novel and clinically important, because DHEA is an endogenous hormone produced by the adrenal glands and elevated in a high proportion of women who have polycystic ovary syndrome, the most common endocrinopathy in reproductive age women. Together, this data suggest a mechanistic link between increased DHEA levels, use of glucose via the PPP, and pregnancy loss.

Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for Ovarian Endometriosis

2021 ◽  
Author(s):  
Mayuko Murakami ◽  
Satoko Osuka ◽  
Ayako Muraoka ◽  
Shotaro Hayashi ◽  
Bayasula Bayasula ◽  
...  
Keyword(s):  
Murine Model ◽  
Stromal Cells ◽  
Ovarian Function ◽  
Interleukin 1 ◽  
Hormonal Treatment ◽  
Reproductive Age ◽  
Ovarian Endometriosis ◽  
Endometrial Stromal Cells ◽  
Nlrp3 Gene ◽  
Gene And Protein Expression

Abstract Background Endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects 10% of women of reproductive age. Ovarian endometriosis (OE) is the most common lesion in endometriosis and may cause infertility in addition to dysmenorrhea. Hormonal treatments for endometriosis suppress ovulation; hence, they are not compatible with fertility. The inflammasome is a complex that includes Nod-like receptor (NLR) family proteins that sense pathogen-/danger‐associated molecular patterns and homeostasis-altering molecular processes. It has been reported that the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing (NLRP) 3 inflammasome, which contributes to the activation of interleukin-1 beta (IL-1β), might be related to the progression of endometriosis. Therefore, the aim of the present study was to evaluate non-hormonal therapies for OE, such as the inhibitors of the NLRP3 inflammasome. Methods The expression of NLRP3 was measured in the eutopic endometrium (EM) of patients with/without endometriosis and OE and stromal cells derived from the endometrium of patients with endometriosis and OE (endometrial stromal cells [ESCs] and cyst-derived stromal cells [CSCs]). The effect of an NLRP3 inhibitor (MCC950) on ESC and CSC survival and IL-1β production was evaluated. We then administered MCC950 to a murine model of OE to evaluate its effects on OE lesions and ovarian function. Results NLRP3 gene and protein expression levels were higher in OE and CSCs than in EM and ESCs, respectively. MCC950 treatment significantly reduced the survival of CSCs but not that of ESCs. Moreover, MCC950 treatment reduced the co-localization of NLRP3 and IL-1β in CSCs and IL-1β concentrations in CSC supernatants. In the murine model, MCC950 treatment reduced OE lesion size compared to phosphate-buffered saline treatment (89 ± 15 vs. 49 ± 9.3 mm3 per ovary; P < 0.05). In addition, IL-1β and Ki67 levels in the OE-associated epithelia and oxidative stress markers of granulosa cells were reduced in the MCC950-treated group. Conclusions These results indicate that NLRP3/IL-1β is involved in the pathogenesis of endometriosis and that NLRP3 inhibitors may be useful for suppressing OE and improving the function of ovaries with endometriosis.

scholarly journals Down-Regulating Hexokinase 2 Inhibits Proliferation of Endometrial Stromal Cells Through a Noncanonical Pathway Involving Phosphorylated-STAT1 in Endometriosis

2021 ◽  
Author(s):  
Shuhui Hou ◽  
Shating Lei ◽  
Haiyan Peng ◽  
Lichun Weng ◽  
Siji Lv ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Cell Function ◽  
Malignant Tumors ◽  
Reproductive Age ◽  
Endometrial Stromal Cells ◽  
Hexokinase 2 ◽  
Proliferation Capacity ◽  
Glycolysis Pathway ◽  
Elevated Expression

Abstract Background: Endometriosis is a benign gynecologic disease that causes chronic pelvic pain, dysmenorrhea and infertility and shares several characteristics with malignant tumors, afflicting women of reproductive age. Hexokinase 2 (HK2) plays a pivotal role as the first rate-limiting enzyme in the metabolic glycolysis pathway, and its abnormal elevation in tumors is associated with tumor genesis and metastasis. However, the expression and role of HK2 in endometriosis remain unclear.Methods: We sequenced the primary endometrial stromal cells from patients with endometrioma and adopted immunohistochemistry, quantitative real-time PCR and western blot to determine the expression of HK2. Then wound healing assays, cell invasion assays, cell proliferation assays were performed to explore the functions of HK2 in endometrial stromal cells. Furthermore, mice models of endometriosis were recruited to observe the effects of HK2 inhibitors in vivo. Lastly, glycolysis metabolism detection and transcriptome sequencing were carried out in HK2-knockdown endometrial stromal cells to analyze the mechanism of HK2 affecting cell function.Results: Endometriotic stromal cells displayed active glycolysis metabolism and elevated expression of HK2. Downregulating HK2 reduced the migration, invasion and proliferation capacity of endometrial stromal cells. Knockdown of HK2 induced upregulation of signal transducer and activator of transcription 1 (STAT1) and their phosphorylation to attenuate the proliferation of endometrial stromal cells.Conclusions: HK2 was associated with the migration, invasion and proliferation of endometrial stromal cells, which might provide new insights into the pathogenesis and treatment of endometriosis.

scholarly journals Peculiarities of intrauterine pathological processes in women of the postmenopauseal period

2021 ◽  
pp. 16-23
Author(s):  
Tetiana Polishchuk ◽  
Serhii Vdovichenko ◽  
Oleksandra Lubkovska ◽  
Dmytro Ledin
Keyword(s):  
Postmenopausal Women ◽  
Stromal Cells ◽  
Endometrial Adenocarcinoma ◽  
Progesterone Receptors ◽  
Uterine Cavity ◽  
Reproductive Age ◽  
Immunohistochemical Method ◽  
Women Of Reproductive Age ◽  
Endometrial Polyps ◽  
Increased Risk

Aim of the research is studying the pecularities of the endometrium pathological processes in postmenopausal women on the basis of the hysteroscopy data evaluation, as well as conduction of histopathological and immunochemical studies. Materials and methods. To study the pecularities of intrauterine pathological processes, 100 postmenopausal women were selected and studied. All women underwent hysteroscopy with separate diagnostic scraping of the uterine cavity. Also, 10 samples of glandular-fibrous endometrial polyps (GFEP) in women of reproductive age and 9 samples of such pathology in the postmenopausal period were studied by immunohistochemical method, using 6 primary specific monoclonal antibodies. Results. The results showed that in 64 (64 %) postmenopausal women pathological changes of the endometrium were presented with GFEP, and in 2 patients (2 %) endometrial adenocarcinoma was found. It was also determined that the nuclei of epithelial and stromal cells of GFEP in postmenopausal women are characterized by lower expression of estrogen and progesterone receptors, compared with women with such formations in the reproductive age. In addition, it was found that in postmenopausal women the expression of the apoptosis inhibitor bcl-2 and aromatase P450 in the epithelial and stromal cells of GFEP was more expressed, and the expression of the Bах antigen, on the contrary, was significantly lower than in women of reproductive age. Conclusions. Fundamental molecular-biological differences of GFEP in postmenopausal women compared with women of reproductive age were revealed. It was found that in postmenopausal women there is a significantly lower dependence of such polyps on the effects of estrogen and progesterone. In addition, the data indicate an increased risk of neoplastic transformation in such women.

Pyrvinium pamoate induces in-vitro suppression of IL-6 and IL-8 produced by human endometriotic stromal cells

2020 ◽  
pp. 096032712096454
Author(s):  
Amin Karamian ◽  
Shahrokh Paktinat ◽  
Sahar Esfandyari ◽  
Hamid Nazarian ◽  
Seyed Ali Ziai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stromal Cells ◽  
Chronic Inflammatory Disease ◽  
Reproductive Age ◽  
Endometrial Stromal Cells ◽  
Mrna Gene ◽  
And Control ◽  
Mrna Gene Expression ◽  
Pyrvinium Pamoate

Endometriosis, a chronic inflammatory disease, is identified by the presence of endometrial tissue outside the uterus. The prevalence of this disease among reproductive-age women is almost 10–15%. High levels of IL-6 and IL-8 have been found in the peritoneal fluid (PF) of women with endometriosis and are involved in its pathogenesis. Isolated stromal cells from 12 ectopic and eutopic endometrial biopsies of women with ovarian endometrioma and also 12 endometrial biopsies of nonendometriotic controls were treated with 1.1 µM pyrvinium pamoate, a Wnt/β-catenin signaling pathway inhibitor, for 72 hrs. Before treatment, mRNA gene expression and secretion of IL-6 and IL-8 were significantly higher in ectopic (EESCs) than eutopic (EuESCs) and control (CESCs) endometrial stromal cells. After treatment, mRNA gene expression and also secretion of IL-6 and IL-8 were significantly reduced. Our Findings showed that pyrvinium pamoate suppresses the mRNA gene expression and secretion of IL-6 and IL-8 in human endometriotic stromal cells. Additional investigations on this compound are required before clinical application.

scholarly journals Downregulation of Circ_0000673 Promotes Cell Proliferation and Migration in Endometriosis Via Suppressing PTEN

2021 ◽  
Author(s):  
Yongwen Yang ◽  
Deying Ban ◽  
Chun Zhang ◽  
Licong Shen
Keyword(s):  
Cell Proliferation ◽  
Western Blotting ◽  
Stromal Cells ◽  
Bioinformatic Analysis ◽  
Reproductive Age ◽  
Luciferase Assay ◽  
Endometrial Stromal Cells ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Endometriosis is a prevalent gynecologic disease, affecting up to 10% of women at reproductive age and approximately 50% of women with infertility. The function of circRNAs in various diseases has been highlighted. Dysregulated expression of circRNAs in endometriosis has been reported and circ_0000673 was significantly deregulated. However, its explicit role in pathogenesis of endometriosis is yet to be identified. Methods: circ_0000673 expression was detected in paried ectopic and eutopic endometrium using qPCR and fluorescent in situ hybridization. Knockdown of circ_0000673 in eutopic and normal endometrial stromal cells were done by transfection with lentivirus vectors. The proliferation activity of endometrial stromal cells was evaluated by CCK-8 assay and colony formation assay, while the migration capacity was valued by wound healing assay. PTEN, PI3K and p-AKT were detected by qPCR and western blotting. Dual luciferase assay was performed to assess the bonding between circ_0000673, PTEN and miR-616-3p.Results: The expression of circ_0000673 was reduced in ectopic endometrium. Knockdown of circ_0000673 significantly induced eutopic and normal endometrial cell proliferation and migration. Bioinformatic analysis predicted that circ_0000673 might sponge miR-616-3p. The effect of circ_0000673 knockdown could be recovered by miR-616-3p inhibitor and enhanced by miR-616-3p mimics. Meanwhile, qPCR and western blotting showed that circ_0000673 knockdown inhibited the expression of PTEN, and subsequently activated PI3K and p-Akt. Furthermore, PTEN was confirmed to be a target of miR-616-3p. Conclusion: The results demonstrated that deregulated expression of circ_0000673 could promote endometriosis progression via sponging miR-616-3p and further regulating PTEN.

scholarly journals Long Non-Coding RNA ADAMTS9-AS1 Represses Ferroptosis of Endometrial Stromal Cells Through Regulating miR-6516-5p/GPX4 Axis in Endometriosis

2021 ◽  
Author(s):  
Yiting Wan ◽  
Cancan Gu ◽  
Jueying Kong ◽  
Jin Sui ◽  
Ling Zuo ◽  
...  
Keyword(s):  
Cell Viability ◽  
Stromal Cells ◽  
Underlying Mechanism ◽  
Current Data ◽  
Reproductive Age ◽  
Endometrial Stromal Cells ◽  
Aberrant Expression ◽  
Non Coding Rna ◽  
And Migration ◽  
Proliferation And Migration

Abstract Endometriosis (EMs) is one of the most frequent diseases in reproductive age women, characterized by the growth of endometrial tissues beyond the uterus. Enhanced proliferative and migratory potential of endometrial stromal cells (ESCs) is the major cause of EMs. Mounting studies have demonstrated that long non-coding RNAs (lncRNAs) exert an important role in regulating the development and progression of EMs. Given the aberrant expression of lncRNA ADAMTS9-AS1 in ectopic endometrium (ecEM), here we investigated the biological effect of ADAMTS9-AS1 on ESCs proliferation and migration and explored the underlying mechanism. The current data showed that the ADAMTS9-AS1 expression was significantly up-regulated in ecEM compared with eutopic endometrium (euEM) in patients with EMs and in a murine model of EMs. Functionally, ADAMTS9-AS1 knockdown in ectopic ESCs (EESCs) decreased cell viability and migration, whereas ADAMTS9-AS1 overexpression in normal ESCs (NESCs) enhanced cell viability and migration. More important, the effect of ADAMTS9-AS1 inhibition on decreasing ESCs viability was significantly blocked by Ferrostatin-1 (Fer-1, a ferroptosis inhibitor), and ADAMTS9-AS1 overexpression repressed Erastin (a ferroptosis activator)-induced cell death. Furthermore, the regulatory role of ADAMTS9-AS1 in ferroptosis was defined and evidenced by increased reactive oxygen species (ROS) level and malonyl dialdehyde (MDA) content, and decreased expression of glutathione peroxidase 4 (GPX4) after ADAMTS9-AS1 inhibition. Mechanistically, ADAMTS9-AS1 functioned as a competing endogenous RNA (ceRNA) via sponging miR-6516-5p to de-repress the expression of GPX4, the critical repressor of ferroptosis. Taken together, these results demonstrate that up-regulated ADAMTS9-AS1 accelerates ESCs proliferation and migration through regulating miR-6516-5p/GPX4-dependent ferroptosis, and may be a potential target for the treatment of EMs.

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