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1.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33808965

RESUMO

Polycystic ovary syndrome (PCOS) is a major anovulatory infertility affecting a great proportion of women of childbearing age and is associated with obesity, insulin resistance and chronic inflammation. Poor endometrial receptivity and recurrent implantation failure are major hurdles to the establishment of pregnancy in women with PCOS. The accumulating body of evidence obtained from experimental and clinical studies suggests a link between inherent adaptive and innate immune irregularities and aberrant endometrial features in PCOS. The use of conventional therapeutic interventions such as lifestyle modification, metformin and ovarian stimulation has achieved limited clinical success in restoring ovulation and endometrial receptivity in women with PCOS. Unlike other immunosuppressive drugs prescribed in the clinical management of autoimmune and inflammatory disorders that may have deleterious effects on fertility and fetal development, preclinical studies in mice and in women without PCOS but with repeated implantation failure revealed potential therapeutic benefits for the use of low-dose tacrolimus in treating female infertility. Improved systemic and ovarian immune functions, endometrial progesterone receptor and coreceptor expressions and uterine vascular adaptation to pregnancy were among features of enhanced progesterone-receptor sensitivity in the low-dose tacrolimus-treated mouse model of the disease. In this review, we have compiled available experimental and clinical data in literature on endometrial progesterone resistance and current therapeutic options, as well as mechanisms of actions and reported outcomes relevant to the potential therapeutic benefits for the use of low-dose tacrolimus in treating PCOS-associated female infertility.


Assuntos
Endométrio/efeitos dos fármacos , Infertilidade Feminina/tratamento farmacológico , Síndrome do Ovário Policístico/tratamento farmacológico , Tacrolimo/uso terapêutico , Relação Dose-Resposta a Droga , Endométrio/anormalidades , Endométrio/patologia , Feminino , Humanos , Infertilidade Feminina/genética , Infertilidade Feminina/patologia , Resistência à Insulina/genética , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/patologia , Gravidez , Doenças Uterinas/genética
2.
Nanoscale ; 13(15): 7334-7347, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33889891

RESUMO

We previously reported that transplantation of menstrual blood-derived stromal cells (MenSCs) significantly improved fertility restoration in intrauterine adhesion (IUA). However, it is difficult to obtain menstrual blood samples in some severe IUA patients who have amenorrhea or oligomenorrhea. Thus, a safe and effective stem cell replacement therapy is necessary to promote endometrial regeneration. Recent studies demonstrated that the effects of MenSCs are partly mediated in a paracrine manner via small extracellular vesicles (sEVs). To explore this possibility, we performed a pre-clinical study to investigate whether concentrated MenSC-derived sEVs (MenSCs-sEVs) are sufficient to repair IUA and the mechanisms underlying their action. Rat IUA models were established by mechanical injury, followed by the administration of MenSCs or MenSCs-sEVs through intrauterine transplantation. Consistent with the efficacy of MenSCs, MenSCs-sEVs effectively recovered the morphology, promoted regeneration of the glands and angiogenesis, and reversed endometrial fibrosis in the IUA uterus. The endometrial receptivity and pregnancy outcome significantly improved after repeated MenSCs-sEVs transplantations. In addition, all rats in the MenSCs-sEVs group had no hematological or biochemical abnormalities. Three-dimensional fluorescence imaging suggested that MenSCs tended to migrate through the bloodstream, whereas MenSCs-sEVs had a better localized therapeutic effect. Moreover, MenSCs and MenSCs-sEVs inhibited the TGFß1/SMAD3 pathway in the IUA endometrium, while promoting the phosphorylation of SMAD1/5/8 and ERK 1/2 and upregulating the expression of BMP7. Thus, MenSCs-sEVs safely and effectively enhanced endometrial restoration, suggesting a promising non-cellular therapy for endometrial regeneration and a key role in MenSC-mediated IUA treatment.


Assuntos
Vesículas Extracelulares , Doenças Uterinas , Animais , Endométrio/patologia , Feminino , Humanos , Ratos , Células Estromais , Aderências Teciduais/patologia , Aderências Teciduais/terapia , Doenças Uterinas/patologia
3.
J Transl Med ; 19(1): 176, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910562

RESUMO

BACKGROUND: Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). An accurate prediction tool for endometrial receptivity (ER) is extraordinarily needed to precisely guide successful embryo implantation. We aimed to establish an RNA-Seq-based endometrial receptivity test (rsERT) tool using transcriptomic biomarkers and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with RIF. METHODS: This was a two-phase strategy comprising tool establishment with retrospective data and benefit evaluation with a prospective, nonrandomized controlled trial. In the first phase, rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 IVF patients with normal WOI timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n = 56; control group, n = 86). pET guided by rsERT was performed in the experimental group and conventional ET in the control group. RESULTS: The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using tenfold cross-validation. The intrauterine pregnancy rate (IPR) of the experimental group (50.0%) was significantly improved compared to that (23.7%) of the control group (RR, 2.107; 95% CI 1.159 to 3.830; P = 0.017) when transferring day-3 embryos. Although not significantly different, the IPR of the experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of the control group (RR, 1.562; 95% CI 0.898 to 2.718; P = 0.111) when transferring blastocysts. CONCLUSIONS: The rsERT was developed to accurately predict the WOI period and significantly improve the pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET. Trial registration Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx.


Assuntos
Implantação do Embrião , Transcriptoma , Biomarcadores , Transferência Embrionária , Endométrio , Feminino , Humanos , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Transcriptoma/genética
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 235-240, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33829697

RESUMO

Objective: To explore the influence for combination of Dingkun Dan with estradiol valerateon in treating rats with thin endometrium with Kidney-Yang deficiency based on Wnt/ß-catenin signaling pathway. Methods: The estrous period 40 rats were randomly divided into the normal control group, the model group, the Dingkun Dan group, the estradiol valerateon group and the combination group, with 8 rats in each group. In addition to the normal control group, the rat model of thin endometrium with Kidney-Yang deficiency was established in other groups. The control group used free diet, the model group was given distilled water, the estradiol valerateon group was treated with progynova by gavage at 0.3 mg/(kg·d) , Dingkun Dan group was treated with Dingkun Dan by gavage at 2.26 g/(kg·d), and the combined group was given Dingkun Dan at 2.26 g/(kg·d) on the basis of progynova at 0.3 mg/(kg·d). After 3 estrous cycles, the rats were killed and harvested. HE staining was used to observe histopathologic changes in endometrium. The expression of VEGF in rats endometrium were detected by immunohistochemistry. The expression of ß-catenin, E-cadherin and MMP-9 protein in rat endometrium was detected by Western blot. Results: Compared with the control group, the uterine cavity was narrowed or enlarged, the endometrium glands and blood vessels were sparse, and the endometrium was thinner significantly in the model group ( P<0.01); the levels of VEGF was decreased significantly ( P<0.01), while ß-catenin, E-cadherin and MMP-9 were increased significantly ( P<0.01). Compared with the model group, more endometrial glands, rich intimal vessels, the endometrium were thickened significantly in the 3 treatment groups ( P<0.01 or P<0.05); the levels of VEGF was increased differently. The protein levels of ß-catenin and E-cadherin were significantly decreased in each treatment group ( P<0.01), and MMP-9 were significantly decreased in the Dingkun Dan group and in the combination group ( P<0.01). Compared with the estradiol valerateon group, the level of ß-catenin in Dingkun Dan group was higher, and MMP-9 was lower ( P<0.05 or P<0.01). The levels of ß-catenin and MMP-9 in the combination group were significantly decreased ( P<0.01). Compared with the combination group, the levels of ß-catenin was increased significantly, while decreased signicantly in Dingkun Dan group ( P<0.01 or P<0.05). Conclusion: Dingkun Dan combined with estradiol valerateon can increase the thicken of the endometrium by up-regulation of VEGF, while down-regulate of ß-catenin, E-cadherin and MMP-9 in rats with Shen-Yang deficiency and thin endometrium.


Assuntos
Estradiol , Via de Sinalização Wnt , Animais , Endométrio/metabolismo , Feminino , Rim , Ratos , Deficiência da Energia Yang , beta Catenina/genética , beta Catenina/metabolismo
5.
Medicine (Baltimore) ; 100(15): e25416, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847639

RESUMO

ABSTRACT: To study the efficacy of using amniotic membrane, balloon and intrauterine device (IUD) as barrier therapy to prevent re-adhesion after hysteroscopic adhesiolysis.A total of 45 patients diagnosed with intrauterine adhesions in Changzhou Maternal and Child Health Hospital from June 2014 to December 2017 were included in this retrospective case control study. According to different postoperative isolation barrier methods, the patients were divided into group A (Foley balloon + fresh amniotic membrane Day1 + IUD Day7) (22 cases) and group B (Foley balloon Day1 + IUD Day7) (23 cases). Three months after the surgery, the second hysteroscopy was performed to observe the condition of the uterine cavity and the improvement of menstruation, and to monitor the thickness of the endometrium.The efficacy of hysteroscopic procedure in group A was significantly higher than that of group B (P < .05). After 3 months of treatment, the improvement rate of menstruation was significantly higher in group A than in group B (P < .05). Endometrial thickness in both group A and B was significantly increased compared with that before the surgery (P < .05). The postoperative endometrium of group A was significantly thicker than that of group B (P < .05).Amniotic membrane-mediated sequential double-barrier method is clinically feasible for preventing recurrent intrauterine adhesions.


Assuntos
Âmnio , Histeroscopia/métodos , Dispositivos Intrauterinos , Cateterismo Urinário/métodos , Doenças Uterinas/cirurgia , Adulto , Estudos de Casos e Controles , Endométrio/fisiopatologia , Feminino , Humanos , Histeroscopia/efeitos adversos , Período Pós-Operatório , Recidiva , Estudos Retrospectivos , Aderências Teciduais
6.
Wiad Lek ; 74(3 cz 1): 388-394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33813438

RESUMO

OBJECTIVE: The aim: To conduct a morphological study of endometrial tissue to identify changes characteristic of viral lesions to develop improved antirelapse treatment of HPE in women of reproductive age. PATIENTS AND METHODS: Materials and methods: We surveyed 90 patients of the gynecological department who sought medical for hyperplastic processes of the endometrium in reproductive age. All women underwent hysteroscopy, the resulting material was subjected to morphological examination. RESULTS: Results: It became known that the virus is involved in the pathogenesis of endometrial hyperplasia. It is likely that it exists in epitheliocytes not only as a "passenger", but also as an etiological factor. It became known that it was in complex hyperplasia with atypia that the percentage reached the highest level, which is a precancerous condition. CONCLUSION: Conclusions: Typical morphological change of the endometrium - multinucleation, multinuclearity and koilocytotic atypia in women of childbearing age with HPE - was revealed. The presence of infectious pathogens in the endometrium of patients with HPE can be regarded as one of the possible triggers for the development of hyperplastic processes.


Assuntos
Hiperplasia Endometrial , Lesões Pré-Cancerosas , Hiperplasia Endometrial/patologia , Endométrio/patologia , Feminino , Humanos , Hiperplasia/patologia , Histeroscopia , Lesões Pré-Cancerosas/patologia , Gravidez
7.
Pan Afr Med J ; 38: 148, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33912318

RESUMO

Introduction: endometrial cancer is the most common type of cancer in the female genital tract. Most patients are diagnosed during postmenopausal periods. This study aimed to investigate the demographic characteristics as well as cutoff value of endometrial thickness and ultrasound characteristics of endometrial cancer in postmenopausal patients. Methods: we retrospectively analyzed 244 postmenopausal women who underwent endometrial sampling from February 2016 to December 2019. Information of patients was obtained through medical records. The patients were divided into two groups according to histopathological results. Group A included patients with endometrial cancer and group B included patients with non-malignant lesions. Data were summarized based on demographic and ultrasound characteristics. Results: hypertension and history of endometrial hyperplasia were associated with the incidence of endometrial cancer in this study. Endometrial cancer was diagnosed in all ranges when the endometrial thickness was ≥5 mm. Endometrial fluid collection, with increased endometrial thickness, was a risk factor associated with endometrial cancer. Conclusion: regardless of symptoms and risk factors, endometrial histological confirmation in postmenopausal women should be conducted immediately if endometrial abnormalities such as an endometrial thickness ≥5 mm or endometrial fluid collection are detected by transvaginal ultrasound.


Assuntos
Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Endométrio/patologia , Pós-Menopausa , Idoso , Hiperplasia Endometrial/diagnóstico por imagem , Neoplasias do Endométrio/diagnóstico por imagem , Endométrio/diagnóstico por imagem , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Ultrassonografia
9.
J Int Med Res ; 49(3): 300060521997718, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33752504

RESUMO

OBJECTIVE: C-X-C motif chemokine ligand 5 (CXCL5), a member of the chemokine family, is associated with remodeling of connective tissues. However, its role in formation of intrauterine adhesions (IUA) remains unclear. We aimed to investigate the expression and mechanism underlying the role of CXCL5 in IUA. METHODS: Expression of CXCL5 in IUA was detected by immunohistochemistry in a rat model of IUA and by real-time PCR and western blotting in patients with IUA. The protein levels of matrix metalloproteinase 9 (MMP9) and transcription factor p65 in human endometrial cells were assessed by western blotting after CXCL5 overexpression. RESULTS: Protein expression of CXCL5 was significantly decreased in the endometria of IUA rats compared with that of control and sham-operated rats. Real-time PCR and western blotting in patients with IUA showed similar results to those from the rat model. After overexpression, CXCL5 significantly upregulated expression of MMP9 and slightly upregulated expression of p65 in human endometrial cells. CONCLUSIONS: CXCL5 plays an important role in IUA formation after endometrial injury. We propose a molecular mechanism to explain formation of IUA, including downregulation of MMP9 by low CXCL5 expression. These findings provide valuable information for the prevention and targeted therapy of IUA.


Assuntos
Doenças Uterinas , Animais , Quimiocina CXCL5/genética , Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Metaloproteinase 9 da Matriz/genética , Ratos , Aderências Teciduais/patologia , Doenças Uterinas/patologia
10.
Eur J Obstet Gynecol Reprod Biol ; 260: 110-113, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33765478

RESUMO

OBJECTIVES: More than 60,000 hysteroscopies are performed every year in the UK for common reasons such as heavy menstrual bleeding (HMB) or postmenopausal bleeding. A significant number of women requiring hysteroscopy receive oral anticoagulants and there is often a reluctance to perform these procedures due to bleeding concerns. STUDY DESIGN: We are presenting the first proof of concept cohort of patients undergoing minor hysteroscopic procedures while on anticoagulant or antiplatelet medication. A variety of minor procedures such as cervical dilatation, targeted endometrial biopsies, Pipelle endometrial biopsies and insertion or removal of intrauterine contraceptive devices were performed alongside hysteroscopy. RESULTS: Completion of planned procedures was feasible in all women due to minimal bleeding despite the ongoing anticoagulation or anti-platelet treatment. CONCLUSION: More research is needed to establish the safety of performing diagnostic and operative hysteroscopies without bridging or interrupting anticoagulation or antiplatelet treatment.


Assuntos
Histeroscopia , Menorragia , Anticoagulantes/efeitos adversos , Endométrio , Estudos de Viabilidade , Feminino , Humanos , Histeroscopia/efeitos adversos , Gravidez , Hemorragia Uterina/induzido quimicamente
11.
J Pak Med Assoc ; 71(Suppl 2)(2): S112-S115, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33785954

RESUMO

OBJECTIVE: Endometriosis is a multifactorial disease that affects 10% of women of childbearing age. Its development is known to be related to the MMP-2 gene. Specifically, the expression of MMP-2 is increase in endometriosis. The aim of this study was to evaluate the correlation between mRNA expression and DNA methylation levels of the MMP-2 gene in peritoneal endometriosis. Methods: This study used a cross-sectional design. The samples included peritoneal endometriosis tissue from women with endometriosis and normal endometrial tissue from women without endometriosis. Twenty samples of each type were taken, and the women were 20-45 years of age. Peritoneal endometriosis tissue was acquired using the laparoscopic technique, while normal endometrial tissue was taken with the microcuretase technique. The mRNA expression of the MMP-2 gene was analysed with qRT-PCR, and the level of DNA methylation of the MMP-2 gene was analysed with a methylation-specific PCR method. RESULTS: The mRNA expression of MMP-2 gene in peritoneal endometriosis tissue was increased, and there were significant differences between peritoneal endometriosis tissue and normal endometrial tissue. The MMP-2 gene was hypermethylated, but there was no significant difference (p = 0.596) between peritoneal endometriosis tissue and endometrial tissue in terms of methylation. This study did not show a significant correlation between mRNA expression and DNA methylation levels of the MMP-2 gene (p = 0.769, r = 0.070). CONCLUSIONS: The increase in MMP-2 gene expression in peritoneal endometriosis tissue is likely not only due to hypermethylation; there are other factors that might play a role.


Assuntos
Endometriose , Metaloproteinase 2 da Matriz , Estudos Transversais , Metilação de DNA , Endometriose/genética , Endométrio , Feminino , Humanos , Metaloproteinase 2 da Matriz/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
12.
Medicine (Baltimore) ; 100(13): e25330, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787629

RESUMO

BACKGROUD: Previous studies have reported that the levels of L1 cell adhesion molecule (L1CAM) indicate poor prognosis of patients with various solid tumors. However, the prognostic significance of L1CAM in endometrial cancer has remained controversial. Herein, we conducted a systematic review and meta-analysis to evaluate the prognostic value of L1CAM in endometrial cancer. METHODS: All studies related to the association between L1CAM expression and clinical characteristics of endometrial cancer were identified by searching the PubMed, MEDLINE, EMBASE, and Web of Science databases. Primary outcomes of the meta-analysis were the hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS). Secondary outcomes were odds ratios (ORs) for clinicopathological characteristics. Publication bias and sensitivity analysis were conducted to ensure reliability of the results. RESULTS: Overall, 17 studies encompassing 7146 patients were eligible for the meta-analysis. Results showed L1CAM overexpression to be significantly associated with decreased overall survival (HR = 2.87, 95% CI; 1.81-4.55, P < .001) and disease-free survival (HR = 3.32, 95% CI; 1.99-5.55, P < .001) in patients with endometrial cancer. High L1CAM expression was also related to adverse clinicopathological characteristics. CONCLUSION: This systematic review demonstrated that high L1CAM expression is correlated with poor survival outcomes and adverse clinicopathological parameters in patients with endometrial cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Endométrio/mortalidade , Endométrio/patologia , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Intervalo Livre de Doença , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco
13.
Maturitas ; 146: 9-10, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33722366

RESUMO

Tuberculosis (TB) is an infectious disease defined by the World Health Organization as a global priority. Extrapulmonary forms include lymph nodal, pleural and urogenital disease (FGTB), which generally affect patients between 20 and 40 years of age, and is rare in postmenopausal women. Its presentation can mimic carcinomatosis due to advanced ovarian and/or endometrial cancer. Non-diagnosis can lead to inappropriate treatment, notably surgical procedures, instead of the standard medical anti-TB chemotherapy.


Assuntos
Tuberculose dos Genitais Femininos/diagnóstico , Doenças Uterinas/diagnóstico , Diagnóstico Diferencial , Endométrio/diagnóstico por imagem , Endométrio/patologia , Feminino , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Tuberculose dos Genitais Femininos/patologia , Doenças Uterinas/patologia
14.
Life Sci ; 275: 119351, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33737084

RESUMO

AIM: Endometrial exosomes carry bioactive agents to uterine epithelial cells and trophectoderm to promote implantation. On the other hand, intrauterine administration of human chorionic gonadotropin (hCG) could improve endometrial receptivity. Therefore, we investigated the delivery of hCG to the endometrial cells by uterine exosomes to increase endometrial receptivity. MAIN METHODS: Exosomes were isolated from uterine fluid and characterized by dynamic light scattering, transmission electron microscopy, and western blotting. The freeze-thaw cycle and sonication methods were used to load hCG into the exosomes. The drug release pattern and uptake of exosomes into the endometrial cells were evaluated. Finally, the influence of hCG loaded-exosomes on the expression of several endometrial receptivity markers was evaluated. KEY FINDINGS: The isolated uterine fluid exosomes had a cup-shaped or spherical morphology with a mean size of 91.8 nm and zeta potential of -9.75 mV. The average loading capacity of exosomes for hCG was 710.05 ± 73.74 and 245.06 ± 95.66 IU/mg using the sonication and freeze-thaw cycle methods, respectively. The effect of hCG loaded-exosomes on the endometrial receptivity was greater than the hCG or exosomes alone. We found that hCG upregulated LIF and Trophinin and downregulated Muc-16 and IGFBP1 genes. Interestingly, the effect of hCG on the expression of LIF and Muc-16 was significantly intensified when used in the form of hCG loaded-exosomes. SIGNIFICANCE: These findings strengthen our hope in using uterine fluid-derived exosome as an effective carrier for proteins or other therapeutic agents to effective delivery into endometrial cells.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Endométrio/metabolismo , Exossomos/metabolismo , Útero/metabolismo , Western Blotting , Células Cultivadas , Implantação do Embrião , Exossomos/ultraestrutura , Feminino , Humanos , Microscopia Eletrônica de Transmissão , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma
15.
Cochrane Database Syst Rev ; 3: CD011424, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33734431

RESUMO

BACKGROUND: Intentional endometrial injury is being proposed as a technique to improve the probability of pregnancy in women undergoing assisted reproductive technologies (ART) such as in vitro fertilisation (IVF). Endometrial injury is often performed by pipelle biopsy and is a common gynaecological procedure with established safety. However, it causes a moderate degree of discomfort/pain and requires an additional pelvic examination. The effectiveness of this procedure outside of ART, in women or couples attempting to conceive via sexual intercourse or with intrauterine insemination (IUI), remains unclear. OBJECTIVES: To assess the effectiveness and safety of intentional endometrial injury performed in infertile women or couples attempting to conceive through sexual intercourse or intrauterine insemination (IUI). SEARCH METHODS: The Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, ISI Web of Knowledge, and clinical trial registries were searched from inception to 21 May 2020, as were conference abstracts and reference lists of relevant reviews and included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated any kind of intentional endometrial injury in women planning to undergo IUI or attempting to conceive spontaneously (with or without ovarian stimulation (OS)) compared to no intervention, a mock intervention, or intentional endometrial injury performed at a different time or to a higher/lower degree. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Primary outcomes were live birth/ongoing pregnancy and pain experienced during the procedure. Due to high risk of bias associated with many of the studies, primary analyses of all review outcomes were restricted to studies at low risk of bias. Sensitivity analysis including all studies was then performed. MAIN RESULTS: We included 23 RCTs (4035 women). Most of these studies included women with unexplained infertility. Intentional endometrial injury versus either no intervention or a sham procedure The primary analysis was restricted to studies at low risk of bias, which left only one study included. We are uncertain whether endometrial injury has an effect on the probability of live birth, as only one study is included in the analysis and the confidence interval is wide (risk ratio (RR) 1.11, 95% confidence interval (CI) 0.78 to 1.59; 1 RCT, 210 participants). Evidence suggests that if the chance of live birth with no intervention/a sham procedure is assumed to be 34%, then the chance with endometrial injury would be 27% to 55%. When all studies were included in the sensitivity analysis, we were uncertain whether endometrial injury improves live birth/ongoing pregnancy, as the evidence was of very low quality (RR 1.71, 95% CI 1.32 to 2.21; 8 RCTs, 1522 participants; I² = 16%). Evidence suggests that if the chance of live birth/ongoing pregnancy with no intervention/a sham procedure is assumed to be 13%, then the chance with endometrial injury would be 17% to 28%. A narrative synthesis conducted for the other primary outcome of pain during the procedure included studies measuring pain on a zero-to-ten visual analogue scale (VAS) or grading pain as mild/moderate/severe, and showed that most often mild to moderate pain was reported (6 RCTs, 911 participants; very low-quality evidence). Higher versus lower degree of intentional endometrial injury Evidence was insufficient to show whether there is a difference in ongoing pregnancy rates (RR 1.29, 95% CI 0.71 to 2.35; 1 RCT, 332 participants; low-quality evidence) between hysteroscopy with endometrial injury and hysteroscopy alone. Evidence suggests that if the chance of ongoing pregnancy with hysteroscopy alone is 10%, then the chance with hysteroscopy with endometrial injury would be 7% to 24%. This study did not report the primary outcomes of live birth and pain during the procedure. Timing of intentional endometrial injury Four trials compared endometrial injury performed in the cycle before IUI to that performed in the same cycle as IUI. None of these studies reported the primary outcomes of live birth/ongoing pregnancy and pain during the procedure. One study compared endometrial injury in the early follicular phase (EFP; Day 2 to 4) to endometrial injury in the late follicular phase (LFP; Day 7 to 9), both in the same cycle as IUI. The primary outcome live birth/ongoing pregnancy was not reported, but the study did report the other primary outcome of pain during the procedure assessed by a zero-to-ten VAS. The average pain score was 3.67 (standard deviation (SD) 0.7) when endometrial injury was performed in the EFP and 3.84 (SD 0.96) when endometrial injury was performed in the LFP. The mean difference was -0.17, suggesting that on average, women undergoing endometrial injury in the EFP scored 0.17 points lower on the VAS as compared to women undergoing endometrial injury in the LFP (95% CI -0.48 to 0.14; 1 RCT, 110 participants; very low-quality evidence). AUTHORS' CONCLUSIONS: Evidence is insufficient to show whether there is a difference in live birth/ongoing pregnancy between endometrial injury and no intervention/a sham procedure in women undergoing IUI or attempting to conceive via sexual intercourse. The pooled results should be interpreted with caution, as the evidence was of low to very low quality due to high risk of bias present in most included studies and an overall low level of precision. Furthermore, studies investigating the effect of timing of endometrial injury did not report the outcome live birth/ongoing pregnancy; therefore no conclusions could be drawn for this outcome. Further well-conducted RCTs that recruit large numbers of participants and minimise bias are required to confirm or refute these findings. Current evidence is insufficient to support routine use of endometrial injury in women undergoing IUI or attempting to conceive via sexual intercourse.


Assuntos
Coito , Endométrio/lesões , Fertilização In Vitro , Infertilidade/terapia , Nascimento Vivo/epidemiologia , Taxa de Gravidez , Aborto Espontâneo/epidemiologia , Adulto , Viés , Feminino , Humanos , Dor/diagnóstico , Dor/etiologia , Dor Processual/diagnóstico , Dor Processual/etiologia , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Técnicas de Reprodução Assistida
16.
Life Sci ; 274: 119332, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33711384

RESUMO

AIMS: Blastocyst implantation is mainly depended on the adhesion between cells and cell matrix. Endometrial adhesion plays an important role in establishing embryo implantation, but the underlying mechanisms are remains unclear. Talin1 is a local adhesion complex protein that is necessary for cell adhesion and movement. However, the role and mechanisms of Talin1 in embryo implantation are still unclear. MAIN METHODS: The expression of Talin1 and Integrin αvß3 was measured in the receptive endometrium from the RIF (Recurrent implantation failure) cohort and NC (normal fertile control group) cohort. A JEG-3 trophoblast and endometrial epithelial cell adhesion model and pregnant mouse model were established. The molecular mechanism of Talin1-mediated cell adhesion was explored by RNA sequencing, RT-qPCR, as well as western blotting assays. KEY FINDINGS: Talin1 enhances endometrial cell adhesion by regulating the Ras signaling pathway, and ultimately facilitates embryo implantation. SIGNIFICANCE: This study revealed the molecular mechanisms of regarding the pathogenesis of RIF caused by endometrial receptivity insufficiency. Further pharmacological research on the Ras signaling pathway would be valuable and might provide new therapeutic targets for RIF patients.


Assuntos
Aborto Habitual/patologia , Adesão Celular , Implantação do Embrião , Endométrio/patologia , Talina/metabolismo , Talina/fisiologia , Proteínas ras/metabolismo , Aborto Habitual/genética , Aborto Habitual/metabolismo , Animais , Apoptose , Proliferação de Células , Células Cultivadas , Endométrio/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Camundongos Knockout , Gravidez , Prognóstico , Talina/genética , Proteínas ras/genética
17.
Mol Med Rep ; 23(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33760149

RESUMO

Endometriosis (EM) is a multifactorial and debilitating chronic benign gynecological disease, but the pathogenesis of the disease is not completely understood. Dysregulated expression of microRNAs (miRNA/miR) is associated with the etiology of EM due to their role in regulating endometrial stromal cell proliferation and invasion. The present study aimed to identify the functions and mechanisms underlying miR­143­3p in EM. To explore the role of miR­143­3p in EM, functional miRNAs were analyzed via bioinformatics analysis. miR­143­3p expression levels in endometriotic stromal cells (ESCs) and normal endometrial stromal cells (NESCs) were measured via reverse transcription­quantitative PCR. The role of miR­143­3p in regulating ESC proliferation and invasion was assessed by performing Cell Counting Kit­8 and Transwell assays, respectively. miR­143­3p expression was significantly upregulated in ESCs compared with NESCs. Functionally, miR­143­3p overexpression inhibited ESC proliferation and invasion, whereas miR­143­3p knockdown promoted ESC proliferation and invasion. Moreover, miR­143­3p inhibited autophagy activation in ESCs, as indicated by decreased green puncta, which represented autophagic vacuoles, decreased microtubule associated protein 1 light chain 3α expression and increased p62 expression in the miR­143­4p mimic group compared with the control group. Moreover, compared with the control group, miR­143­3p overexpression significantly decreased the expression levels of autophagy­related 2B (ATG2B), a newly identified target gene of miR­143­3p, in ESCs. ATG2B overexpression reversed miR­143­3p overexpression­mediated inhibition of ESC proliferation and invasion. Collectively, the results of the present study suggested that miR­143­3p inhibited EM progression, thus providing a novel target for the development of therapeutic agents against EM.


Assuntos
Proteínas Relacionadas à Autofagia/genética , Autofagia/genética , Endometriose/genética , MicroRNAs/genética , Proteínas de Transporte Vesicular/genética , Adulto , Movimento Celular/genética , Proliferação de Células/genética , Endometriose/patologia , Endométrio/metabolismo , Endométrio/patologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Regulação da Expressão Gênica/genética , Humanos , Pessoa de Meia-Idade , Células Estromais/metabolismo , Células Estromais/patologia
18.
Klin Lab Diagn ; 66(2): 87-94, 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33734641

RESUMO

A cytological examination of uterine cavity material has proven to be the effective method of detecting and clarifying the diagnosis of cancer and non-tumor endometrial diseases. However, sometimes there are difficulties in interpreting the results in a traditional (classical) cytological examination, due to high level of inadequate samples: the presence of mucus, a large number of blood elements, structures of poorly visible cells in the wrong preparation of the smear. At present, the method of liquid cytology, based on the technology of preparation of standard thin-layer cytological preparations from liquid cell suspension, is increasingly developed and widespread. These slides, if necessary, can be used for morphometry, cytochemical, immunocytochemical studies etc. It is also possible to prepare cell blocks from this material, and to obtain information about the histological structure if small pieces of tissue are presented in cytological material, moreover, to use these blocks for immunohistochemical reactions. Material from the uterine cavity may contain tumor cells from ovarian, tubal or other non- endometrial carcinoma, and it is necessary to obtain information about their origin, to verify the morphological diagnosis and to determine the management and treatment of patients, as a lot of problems concerning ovarian and endometrial cancer remains unclear. Examination of aspirates and scrapes from the uterine cavity using advanced molecular techniques, together with existing examination methods, can help to form risk groups for uterine, tubal, ovarian and even peritoneal tumors. The review of literature contains comparative characteristics of different methods and their combinations, which allow improving diagnostics of non-tumor lesions and endometrial tumors.


Assuntos
Neoplasias do Endométrio , Endométrio , Citodiagnóstico , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Feminino , Humanos
19.
Adv Exp Med Biol ; 1285: 1-15, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33770399

RESUMO

The pregnancy recognition signal from the conceptus (embryo/fetus and associated membranes) to the mother is interferon tau (IFNT) in ruminants and estradiol, possibly in concert with interferons gamma and delta in pigs. Those pregnancy recognition signals silence expression of interferon stimulated genes (ISG) in uterine luminal (LE) and superficial glandular (sGE) epithelia while inducing expression of genes for transport of nutrients, including glucose and amino acids, into the uterine lumen to support growth and development of the conceptus. In sheep and pigs, glucose not utilized immediately by the conceptus is converted to fructose. Glucose, fructose, serine and glycine in uterine histotroph can contribute to one carbon (1C) metabolism that provides one-carbon groups for the synthesis of purines and thymidylate, as well as S-adenosylmethionine for epigenetic methylation reactions. Serine and glycine are transported into the mitochondria of cells and metabolized to formate that is transported into the cytoplasm for the synthesis of purines, thymidine and S-adenosylmethionine. The unique aspects of one-carbon metabolism are discussed in the context of the hypoxic uterine environment, aerobic glycolysis, and similarities in metabolism between cancer cells and cells of the rapidly developing fetal-placental tissues during pregnancy. Further, the evolution of anatomical and functional aspects of the placentae of sheep and pigs versus primates is discussed in the context of mechanisms to efficiently obtain, store and utilize nutrients required for rapid fetal growth in the last one-half of gestation.


Assuntos
Embrião de Mamíferos , Interferon Tipo I , Animais , Carbono , Endométrio , Feminino , Desenvolvimento Fetal , Placenta , Gravidez , Ovinos , Suínos , Útero
20.
Adv Exp Med Biol ; 1285: 17-28, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33770400

RESUMO

During the peri-implantation period, conceptuses [embryo and placental membranes, particularly the trophectoderm (Tr)] of farm animals (e.g., sheep and pigs) rapidly elongate from spherical to tubular to filamentous forms. In concert with Tr outgrowth during conceptus elongation, the Tr of sheep and pig conceptuses attaches to the endometrial luminal epithelium (LE) to initiate placentation. In sheep, binucleate cells (BNCs) begin to differentiate from the mononuclear trophectoderm cells and migrate to the endometrial LE to form syncytial plaques. These events require Tr cells to expend significant amounts of energy to undergo timely and extensive proliferation, migration and fusion. It is likely essential that conceptuses optimally utilize multiple biosynthetic pathways to convert molecules such as glucose, fructose, and glutamine (components of histotroph transport by sheep and pig endometria into the uterine lumen), into ATP, amino acids, ribose, hexosamines and nucleotides required to support early conceptus development and survival. Elongating and proliferating conceptus Tr cells potentially act, in a manner similar to cancer cells, to direct carbon generated from glucose and fructose away from the TCA cycle for utilization in branching pathways of glycolysis, including the pentose phosphate pathway, one-carbon metabolism, and hexosamine biosynthesis. The result is a limited availability of pyruvate for maintaining the TCA cycle within mitochondria, and Tr cells replenish TCA cycle metabolites via a process known as anaplerosis, primarily through glutaminolysis to convert glutamine into TCA cycle intermediates. Here we describe the cell-specific expression of enzymes required for serine biosynthesis, one-carbon metabolism and glutaminolysis at the uterine-placental interface of sheep and pigs, and propose that these biosynthetic pathways are essential to support early placental development including Tr elongation, cell migration, cell fusion and implantation by ovine and porcine conceptuses.


Assuntos
Animais Domésticos , Serina , Animais , Implantação do Embrião , Embrião de Mamíferos , Endométrio , Feminino , Gravidez , Ovinos , Suínos , Útero
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