scholarly journals miR-21 and Pellino-1 Expression Profiling in Autoimmune Premature Ovarian Insufficiency

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xinran Li ◽  
Jiaxin Xie ◽  
Qingru Wang ◽  
Huihua Cai ◽  
Chuhai Xie ◽  
...  
Keyword(s):  
Mouse Models ◽  
Clinical Characteristics ◽  
Endocrine Function ◽  
Premature Ovarian Insufficiency ◽  
Inflammatory Factors ◽  
Control Group ◽  
Mrna Levels ◽  
Ovarian Insufficiency ◽  
Immune Parameters ◽  
Putative Target

Background. Premature ovarian insufficiency (POI) represents the hypergonadotropic hypoestrogenic symptoms that result in the loss of ovarian follicles. 5-30% POI cases are suggested to be involved in autoimmune etiology. MicroRNA-21 (miR-21) plays a vital role in ovarian folliculogenesis via regulating and interacting with multiple target genes. Here, we conduct the target prediction of miR-21, identify the expression and correlation of miR-21 and its putative target Pellino-1 (Peli1), and confirm their relationship with clinical characteristics in autoimmune POI. Methods. Bioinformatic analysis was conducted to screen the miR-21 putative target gene. Autoimmune POI mouse models were established by ZP3 immunization. Serum miR-21, Peli1 mRNA of peripheral blood mononuclear cells (PBMCs) and regulatory T cells (Tregs), general status, spleen Tregs ratio, inflammatory factors, ovarian endocrine function, and ovarian structure were evaluated. For autoimmune POI patients, serum miR-21, PBMCs Peli1 mRNA levels, general data, immune parameters, hormone levels, and ultrasound examinations were obtained. The correlations of miR-21 with Peli1 and clinical characteristics in patients were analyzed. Results. Peli1 was selected based on four microRNA prediction databases and literature retrieval. In mouse models, serum miR-21 level, PBMCs and Tregs Peli1 mRNA, and spleen Tregs ratio were 0.61±0.09, 0.12±0.12, 0.27±0.23 and 4.82±0.58, respectively, lower than those in the control group. In patients, miR-21 level (0.60±0.14) and Peli1 mRNA (0.30±0.14) were lower than those in the control group (1.01±0.07 and 1.63±0.54); miR-21 was positively related with Peli1, AMH, E2, the size of the uterus, and ovarian volume and negatively related with FSH, LH, and the number of positive immune parameters (AOAb, EMAb, ACL, ANA, ds-DNA, ACA, IgG, IgA, IgM, IgE, C3, and C4). Conclusions. Low expressions of miR-21 and Peli1 were detected in autoimmune POI mice and patients. Positive correlation between miR-21 and Peli1 was observed in autoimmune POI patients, suggesting that miR-21 and Peli1 might be associated with the pathogenesis of autoimmune POI.

Platelet-Rich Plasma Suppresses Inflammation Reaction of Rat Articular Chondrocytes via Wingless-Related Integration Site/β-Catenin Axis

2021 ◽  
Vol 11 (7) ◽  
pp. 1372-1376
Author(s):  
Wei Wang ◽  
Weiwei Ma ◽  
Xu Li ◽  
Yihui Huang ◽  
Xinyu Cao
Keyword(s):  
Second Generation ◽  
Articular Chondrocytes ◽  
Glycogen Synthase ◽  
Integration Site ◽  
Platelet Rich Plasma ◽  
Inflammatory Factors ◽  
Blue Staining ◽  
Saline Control ◽  
Control Group ◽  
Mrna Levels

Our study aims to elucidate the role of platelet-rich plasma (PRP) in rats chondrocytes inflammation and mechanism. PRP was obtained from 8 weeks old rats. Then, the knee joint of bilateral hind limbs was dissected and articular chondrocytes were obtained in super-clean table after dislocation and identified at the second generation during culture and passage. Chondrocytes were divided into control group 1 (addition of saline), control group 2 (IWP-2, Wnt/β-catenin axis inhibitor) and experimental group (PRP) followed by analysis of mRNA levels of glycogen synthase kinase-3 (GSK-3β), low-density lipoprotein receptor-associated protein 5 (LRP5), Wnt1 and β-catenin by RT-PCR, IL-1 and TNF-α after 1 week by ELISA. The second generation articular chondrocytes presented polygonal or triangular cell morphology, positive for collagen II and toluidine blue staining. PRP addition significantly reduced GSK-3β and LRP5 mRNA level, and increased β-catenin and Wnt1 mRNA levels in chondrocytes. Meanwhile, it suppressed IL-1 and TNF-α secretion and Wnt protein production inhibitor 2. PRP might suppresses inflammatory factors production of rat articular chondrocytes through inhibiting Wnt/β-catenin axis.

Clinical characteristics and genetic analysis in women with premature ovarian insufficiency

Maturitas ◽  
2013 ◽  
Vol 74 (1) ◽  
pp. 61-67 ◽  
Author(s):  
Eleonora Ferrarini ◽  
Laura Russo ◽  
Franca Fruzzetti ◽  
Patrizia Agretti ◽  
Giuseppina De Marco ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Clinical Characteristics ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Insufficiency

scholarly journals Premature Ovarian Insufficiency: New Perspectives on Genetic Cause and Phenotypic Spectrum

2016 ◽  
Vol 37 (6) ◽  
pp. 609-635 ◽  
Author(s):  
Elena J. Tucker ◽  
Sonia R. Grover ◽  
Anne Bachelot ◽  
Philippe Touraine ◽  
Andrew H. Sinclair
Keyword(s):  
Mouse Models ◽  
Genetic Basis ◽  
Current Knowledge ◽  
Premature Ovarian Insufficiency ◽  
Ovarian Activity ◽  
Substantial Evidence ◽  
Ovarian Insufficiency ◽  
Phenotypic Spectrum ◽  
Disease Mechanisms

Abstract Premature ovarian insufficiency (POI) is one form of female infertility, defined by loss of ovarian activity before the age of 40 and characterized by amenorrhea (primary or secondary) with raised gonadotropins and low estradiol. POI affects up to one in 100 females, including one in 1000 before the age of 30. Substantial evidence suggests a genetic basis for POI; however, the majority of cases remain unexplained, indicating that genes likely to be associated with this condition are yet to be discovered. This review discusses the current knowledge of the genetic basis of POI. We highlight genes typically known to cause syndromic POI that can be responsible for isolated POI. The role of mouse models in understanding POI pathogenesis is discussed, and a thorough list of candidate POI genes is provided. Identifying a genetic basis for POI has multiple advantages, such as enabling the identification of presymptomatic family members who can be offered counseling and cryopreservation of eggs before depletion, enabling personalized treatment based on the cause of an individual's condition, and providing better understanding of disease mechanisms that ultimately aid the development of improved treatments.

scholarly journals Association between Serum Vitamin A Levels and Premature Ovarian Insufficiency Risk

2021 ◽  
Author(s):  
Yang Song ◽  
Peiqiong Chen ◽  
Wenxian Xu ◽  
Yizhou Huang ◽  
Yingxian Jia ◽  
...  
Keyword(s):  
Vitamin A ◽  
Vitamin A Deficiency ◽  
Lipid Level ◽  
Ovarian Tissue ◽  
Serum Vitamin ◽  
Premature Ovarian Insufficiency ◽  
Control Group ◽  
Binary Logistic Regression Analysis ◽  
Ovarian Insufficiency ◽  
Negatively Associated

Abstract Purpose: The aim of the study was to explore the association between serum vitamin A levels and premature ovarian insufficiency (POI). Methods: In this cross-sectional survey, women with POI (n = 47) and normo-ovulatory controls (n = 67) were enrolled from December 2016 to May 2018 in Zhejiang, China. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), vitamin A, and total cholesterol (TC) were measured for each participant. The association of vitamin A levels with POI risk was assessed using binary logistic regression analysis. Results: Serum vitamin A levels seems slightly higher in the POI group than in the control group (728.00 ± 176.00 vs 503.93 ± 145.64 µg/L, p = 0.133). But after adjust with serum lipid level, serum vitamin A/TC ratio was significantly lower in the POI group than in the control group (143.14 ± 35.86 vs 157.56 ± 35.21 µg/mmol, p = 0.035). Further, serum vitamin A/TC ratio was significantly and negatively associated with POI risk [unadjusted odds ratio (OR) = 0.988, 95% confidence interval (CI): 0.977–0.999, p = 0.039]. The same trend was found after adjusting for confounding factors (age, BMI, annual household income, and education) (OR = 0.986, 95% CI: 0.972–0.999, p = 0.040). Conclusion: Serum vitamin A/TC ratio was negatively associated with POI risk, indicating that vitamin A deficiency may be a risk factor for POI development. Serum vitamin A/TC ratio may serve as a predictive factor for POI incidence. Thus, vitamin A may serve a protective role in ovarian tissue.

scholarly journals Serum Anti-Müllerian Hormone Levels and Risk of Premature Ovarian Insufficiency in Female Childhood Cancer Survivors: Systematic Review and Network Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6331
Author(s):  
Marco Torella ◽  
Gaetano Riemma ◽  
Pasquale De Franciscis ◽  
Marco La Verde ◽  
Nicola Colacurci
Keyword(s):  
Systematic Review ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Ovarian Reserve ◽  
Meta Analysis ◽  
Childhood Cancer Survivors ◽  
Premature Ovarian Insufficiency ◽  
Control Group ◽  
Ovarian Insufficiency ◽  
Increased Risk

Background: Female childhood cancer survivors (CCS) might have impaired ovarian reserves, especially after alkylating agents or radiotherapy. The purpose of this systematic review and network meta-analysis is to evaluate the role of serum anti-Müllerian hormone (AMH) for ovarian reserve screening and the risk of premature ovarian insufficiency (POI) according to the subtype of childhood cancer. (2) Methods: PRISMA-NMA guidelines were followed. We carried out a network meta-analysis based on a random effects model for mixed multiple treatment comparisons to rank childhood cancers effects on fertility by surface under the cumulative ranking curve (SUCRA). Studies were selected only if they had an age-matched control group. Quality assessment was performed using Newcastle–Ottawa Scale. The co-primary outcomes were mean AMH levels and the incidence of POI. (3) Results: A total of 8 studies (1303 participants) were included. Women treated for a neuroblastoma during infancy were more likely to be ranked first for impaired AMH levels (SUCRA = 65.4%), followed by mixed CCS (SUCRA = 29.6%). The greatest rates of POI were found in neuroblastoma survivors (SUCRA = 42.5%), followed by acute lymphoid leukemia (SUCRA = 26.3%) or any other neoplasia (SUCR A= 20.5%). (4) Conclusions: AMH represents a trustworthy approach for ovarian reserve screening. Direct and indirect comparisons found no differences in mean AMH levels and POI risk between subtypes of CCS and healthy controls. SUCRA analysis showed that female neuroblastoma survivors were more at risk for reduced serum AMH levels and increased risk of POI.

scholarly journals Whole-exome sequencing in patients with premature ovarian insufficiency: early detection and early intervention

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Hongli Liu ◽  
Xiaoli Wei ◽  
Yanwei Sha ◽  
Wensheng Liu ◽  
Haijie Gao ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Ovarian Function ◽  
In Silico Analysis ◽  
Premature Ovarian Insufficiency ◽  
Control Group ◽  
Genetic Etiology ◽  
Ovarian Insufficiency ◽  
Pathogenic Variants ◽  
Whole Exome

Abstract Background The loss of ovarian function in women, referred to as premature ovarian insufficiency (POI), is associated with a series of concomitant diseases. POI is genetically heterogeneous, and in most cases, the etiology is unknown. Methods Whole-exome sequencing (WES) was performed on DNA samples obtained from patients with POI, and Sanger sequencing was used to validate the detected potentially pathogenic variants. An in silico analysis was carried out to predict the pathogenicity of the variants. Results We recruited 24 patients with POI and identified variants in POI-related genes in 14 patients, including bi-allelic mutations in DNAH6, HFM1, EIF2B2, BNC, and LRPPRC and heterozygous variants in BNC1, EIF2B4, FOXL2, MCM9, FANCA, ATM, EIF2B3, and GHR. No variants in the above genes were detected in the WES data obtained from 29 women in a control group without POI. Determining a clear genetic etiology could significantly increase patient compliance with appropriate intervention strategies. Conclusions Our study confirmed that POI is a genetically heterogeneous condition and that whole-exome sequencing is a powerful tool for determining its genetic etiology. The results of this study will aid researchers and clinicians in genetic counseling and suggests the potential of WES for the detection of POI and thus early interventions for patients with POI.

scholarly journals Encapsulation of ovarian allograft precludes immune rejection and promotes restoration of endocrine function in immune-competent ovariectomized mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
James Ronald Day ◽  
Anu David ◽  
Mayara Garcia de Mattos Barbosa ◽  
Margaret Ann Brunette ◽  
Marilia Cascalho ◽  
...  
Keyword(s):  
Cardiovascular Health ◽  
Ovarian Tissue ◽  
Hormone Replacement ◽  
Feedback Regulation ◽  
Lymphocytic Infiltration ◽  
Endocrine Function ◽  
Control Group ◽  
Immune Rejection ◽  
Ovarian Insufficiency ◽  
Ovariectomized Mice

Abstract Premature ovarian insufficiency (POI) is a significant complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. POI is particularly devastating for young girls reaching puberty, because it irreversibly affects their physical and cognitive development. Changes occurring during puberty determine their height, bone health, insulin responsiveness, lipid metabolism, cardiovascular health and cognition. The only available treatment for POI during puberty is hormone replacement therapy (HRT), which delivers non-physiological levels of estrogen, lacks other ovarian hormones and pulsatility, and is not responsive to feedback regulation. Here we report that ovarian allografts encapsulated in a hydrogel-based capsule and implanted in ovariectomized mice restore ovarian endocrine function in immune competent mice. Ovarian tissue from BALB/c mice was encapsulated in poly(ethylene-glycol) (PEG) hydrogels, with a proteolytically degradable core and a non-degradable shell. The dual capsules were implanted subcutaneously in immune competent ovariectomized C57BL/6 mice for a period of 60 days. As expected, non-encapsulated ovarian allografts implanted in a control group sensitized the recipients as confirmed with donor-specific IgG in the serum, which increased 26-fold in the 3 weeks following transplantation (p = 0.02) and infiltration of the graft with CD8 T cells consistent with allo-immunity. In contrast, encapsulation in the Dual PEG capsules prevented sensitization to the allograft in all the recipients with no evidence of lymphocytic infiltration. In summary, the approach of hydrogel-based immunoisolation presents a minimally invasive and robust cell-therapy to restore hormonal balance in ovarian insufficiency. This report is the first to demonstrate the application of a tunable PEG-based hydrogel as an immunoisolator of allogeneic ovarian tissue to restore endocrine function in ovariectomized mice and prevent cell-mediated immune rejection in immune competent mice.

scholarly journals FTZ Ameliorates Diabetic Cardiomyopathy by Inhibiting Inflammation and Cardiac Fibrosis in the Streptozotocin-Induced Model

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Lexun Wang ◽  
Huijuan Wu ◽  
Yanyue Deng ◽  
Shengxi Zhang ◽  
Quxing Wei ◽  
...  
Keyword(s):  
Body Weight ◽  
Signaling Pathways ◽  
Diabetic Cardiomyopathy ◽  
Functional Enrichment ◽  
Inflammatory Factors ◽  
Interleukin 12 ◽  
Network Pharmacology ◽  
Control Group ◽  
Therapeutic Effects ◽  
Mrna Levels

Background. The pathogenesis and clinical features of diabetic cardiomyopathy (DCM) have been well studied in the past decade; however, effective approaches to prevent and treat this disease are limited. Fufang Zhenzhu Tiaozhi (FTZ) formula, a traditional Chinese prescription, is habitually used to treat dyslipidemia and diabetes. Recently, several studies have reported the therapeutic effects of FTZ on cardiovascular diseases. However, the effects of FTZ on DCM have not yet been fully elucidated. This study investigated the effects of FTZ on DCM and determined the mechanisms underlying its efficacy. Methods. Diabetes was induced in mice by intraperitoneal injection of streptozotocin; the mice were randomly divided into a control group (Con), diabetes group (DCM), and diabetes-treated with FTZ (DCM + FTZ). Myocardial structural alterations, fibrosis biomarkers, and inflammation were observed. Besides, the potential targets and their related signaling pathways were analyzed using network pharmacology and further verified by Western blot. Results. Diabetic mice showed significant body weight loss, hyperglycemia, and excessive collagen content in the cardiac tissue, while serum and myocardial inflammatory factors significantly increased. Nerveless, treatment with FTZ for 1 month significantly improved body weight, attenuated hyperglycemia, and alleviated diabetes-associated myocardial structure and function abnormalities. Furthermore, the serum levels of interleukin 12 (IL-12) and chemokine (C–C motif) ligand 2 (CCL2) as well as the mRNA levels of cardiac IL-12, IL-6, and C–C motif chemokine receptor 2 (Ccr2) reduced after FTZ treatment. Additionally, a total of 67 active compounds and 76 potential targets related to DCM were analyzed. Pathway and functional enrichment analyses showed that FTZ mainly regulates inflammation-related pathways, including MAPK and PI3K-AKT signaling pathways. Further investigation revealed that the activities of STAT3, AKT, and ERK were augmented in diabetic hearts but decreased in FTZ-treated cardiac tissues. Conclusion. Our results suggest that FTZ exhibits therapeutic properties against DCM by ameliorating hyperglycemia-induced inflammation and fibrosis via at least partial inhibition of AKT, ERK, and STAT3 signaling pathways.

scholarly journals Influence of Sexual Function on the Social Relations and Quality of Life of Women with Premature Ovarian Insufficiency

2018 ◽  
Vol 40 (02) ◽  
pp. 066-071 ◽  
Author(s):  
Daniela Yela ◽  
Patricia Soares ◽  
Cristina Benetti-Pinto
Keyword(s):  
Quality Of Life ◽  
Sexual Function ◽  
Assessment Instrument ◽  
Premature Ovarian Insufficiency ◽  
World Health ◽  
Control Group ◽  
Ovarian Insufficiency ◽  
The Social ◽  
The Impact

Objective To evaluate the impact of sexual function (SF) in the quality of life (QoL) of women with premature ovarian insufficiency (POI). Methods Case-control study in which 80 women with POI were evaluated using estrogen plus progestogen therapy, compared with 80 women matched by age (±2 years) and presenting preserved gonadal function. Sexual function was evaluated using the Female Sexual Function Index (FSFI), and the QoL was evaluated using the World Health Organization's (WHO) QoL assessment instrument (WHOQoL-BREF). Results The mean age of the women with POI and of the control group was 38.4 ± 7.3 years and 38.1 ± 7.3 years respectively. The QoL, was worse among the POI group, and there were significant differences in the physical (63.4 ± 17.4 and 72.7 ± 15.2 respectively, p = 0.0004) and psychological (63.2 ± 14.6 and 69.3 ± 13.9 respectively, p = 0.0075) domains among this group when compared with the control group. Women with POI presented significantly lower arousal, lubrication, orgasm and satisfaction, more dyspareunia and a worse FSFI scores when compared with the control group. All aspects of SF correlate directly with the worsening of the QoL regarding social relationships. Conclusion Women with POI showed worse QoL and SF than the control group. The psychological aspects (desire, excitement, orgasm and sexual satisfaction) of SF had greater influence on the parameters of the QoL, while the physical aspects (pain and lubrication) had a low impact on the QoL. The poor SF in women with POI is directly correlated with a worsening across multiple domains of the QoL; however, the negative impact is particularly important in the social domain. These results suggest that the improvement in sexuality can improve the social interactions of women with POI.

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