Background: This study aimed to evaluate the application value of sperm acrosome integrity rate in male fertility assessment, its impact on in vitro fertilization (IVF) outcomes, and its predictive value for low IVF fertilization rates. Methods: (1) Semen analysis and sperm acrosome integrity rate testing were performed on 82 male outpatients from the andrology department of our hospital. Correlations between acrosome integrity rate and semen parameters were statistically analyzed. (2) Semen samples from 51 couples undergoing IVF were processed and assessed for both semen parameters and sperm acrosome integrity rate. Correlations between acrosome integrity rate and IVF fertilization outcomes were examined. Results: (1) The sperm acrosome integrity rate was negatively correlated with abstinence duration (p < 0.05) and positively correlated with sperm concentration, progressive motility, and vitality (p < 0.05). (2) The sperm acrosome integrity rate showed a significant positive correlation with IVF fertilization rate (p < 0.05). (3) Logistic regression analysis demonstrated that sperm acrosome integrity rate had a positive effect on IVF fertilization rate. (4) Receiver operating characteristic (ROC) curve analysis indicated that the optimal threshold of sperm acrosome integrity rate for predicting low IVF fertilization rate (<50%) was 95.75%. Conclusions: (1) Sperm acrosome integrity rate is not an independent index but is correlated with semen parameters. (2) It is positively correlated with IVF fertilization rate and can be used as a predictive indicator for low fertilization outcomes in IVF.

BACKGROUND: Ovarian tissue cryopreservation for fertility preservation carries a risk of malignant cell re-seeding. Artificial ovary is a promising method to solve such a problem. However, ovary decellularization protocols are limited. Hence, further studies are necessary to get better ovarian decellularization techniques for the construction of artificial ovary scaffolds. OBJECTIVE: To establish an innovative decellularization technique for whole porcine ovaries by integrating liquid nitrogen with chemical agents to reduce the contact time between the scaffolds and chemical reagents. MATERIALS AND METHODS: Porcine ovaries were randomly assigned to three groups: novel decellularized group, conventional decellularized group and fresh group. The ovaries in the novel decellularized group underwent three cycles of freezing by liquid nitrogen and thawing at temperatures around 37??C before decellularization. The efficiency of the decellularization procedure was assessed through histological staining and DNA content analysis. The maintenance of ovarian decellularized extracellular matrix(ODECM) constituents was determined by analyzing the content of matrix proteins. Additionally, we evaluated the biocompatibility of the decellularized extracellular matrix(dECM) by observing the growth of granulosa cells on the ODECM scaffold in vitro.RESULTS: Hematoxylin and eosin staining, DAPI staining and DNA quantification techniques collectively confirm the success of the novel decellularization methods in removing cellular and nuclear components from ovarian tissue. Moreover, quantitative assessments of ODECM contents revealed that the novel decellularization technique preserved more collagen and glycosaminoglycan compared to the conventional decellularized group (P<0.05). Additionally, the novel decellularized scaffold exhibited a significantly higher number of granulosa cells than the conventional scaffold during in vitro co-culture (P<0.05). CONCLUSION: The novel decellularized method demonstrated high efficacy in eliminating DNA and cellular structures while effectively preserving the extracellular matrix. As a result, the novel decellularized method holds significant promise as a viable technique for ovarian decellularization in forthcoming studies.

OBJECTIVE:To investigate the prognostic significance of molecular classification on treatment outcomes of fertility-sparing treatment (FST) in early-stage endometrial cancer (EC), and its potential in optimizing fertility-sparing management. METHODS:Patients with early-stage EC who received FST with ProMisE classification were investigated. Oncological and reproductive outcomes were compared across four molecular subtypes. Factors influencing complete response (CR) were analyzed. RESULTS:Among 116 molecularly classified patients, 80 were evaluated for therapeutic effects, including 64 (80.0 %) p53wt, 7 (8.7 %) MMR-D, 5 (6.3 %) POLE EDM, and 4 (5.0 %) p53abn. Overall CR rates were comparable across four molecular subtypes, with 92.2 % of p53wt, 71.4 % of MMR-D, 100.0 % of POLE EDM, and 75.0 % of p53abn (P = 0.145). MMR-D patients needed the longest median treatment time to achieve CR (7.9 months, range 3.5-15.9), while POLE EDM required the shortest (3.0 months, range 2.8-6.4), followed by p53abn (3.5 months, range 3.0-3.7) and p53wt (3.7 months, range 2.2-22.8) (P = 0.049). Among 14 p53wt patients with superficial myometrial invasion (MI) or G2 histology, 13 (92.9 %) achieved CR, and of 8 who attempted to conceive,4 delivered. Multivariable analysis identified MMR-D, superficial MI and insulin resistance negatively predicted CR, while POLE EDM was a positive factor. CONCLUSIONS:Molecular classification of EC may serve as a tool for predicting response to FST and assist in identifying candidates for FST. POLE EDM patients tended to obtain promising outcomes. MMR-D cases should be cautiously administrated for FST with close surveillance. Patients with p53wt demonstrated favorable outcomes, including those with superficial MI or G2 EC. Patients with endometrium-confined p53abn tumors may benefit from FST. However, given the small sample sizes of certain subtypes, further investigation is necessary to validate these findings.

This study aimed to determine changes in uterine artery Doppler parameters in unexplained recurrent pregnancy loss (URPL) and to explore serum markers possibly associated with them. This retrospective case–control study included 107 URPL women and 107 control women. The mean pulsatility index (PI), resistive index (RI), and systolic-to-diastolic values for uterine arteries in URPL women were significantly higher than those in the controls (P < 0.05). The cutoff values of PI and RI differentiating the women with URPL from the controls were confirmed by ROC and Youden’s index. Given a PI cutoff value of 2.6, the prevalence of URPL was significantly elevated in the high-PI group (74.58

Recurrent spontaneous abortion (RSA) is typically defined as two or more consecutive spontaneous miscarriage with global incidence of 1%-5%. Among them, about 50% cases were with unknown causes, namely unexplained recurrent spontaneous abortion (URSA). Studies showed that URSA may be related to the maternal-fetal immune imbalance while the exact etiology and pathogenesis underlying URSA remains unclear. At present, it is still lack of recognized effective treatments for URSA. Various treatments such as lymphocyte immunotherapy (LIT), intravenous immunoglobulin (IVIG), immunosuppressant, immunomodulator, progesterone and anticoagulant therapy have been tried in URSA women although efficacy and safety of certain treatments are controversial. Here we summarize current status and advances in research on diagnosis and treatments of URSA, especially treatments such as LIT, IVIG, immunosuppressant, granulocyte colony-stimulating factor (G-CSF), intralipid, progesterone, anticoagulant, vitamin D, herbal medicine and preimplantation genetic testing for aneuploidies (PGT-A), aiming to provide a reference for doctors on choosing strategies for URSA patients.

PURPOSE:This study aims to assess whether antibiotic therapy for chronic endometritis (CE) could improve subsequent IVF outcomes in patients with recurrent implantation failure (RIF). METHODS:Studies that explore CE treatment in patients with RIF were retrieved from PubMed, EMBASE, Wanfang, and Google Scholar up to Jan 31, 2022. All retrieved studies were selected according to the inclusion and exclusion criteria. The main outcome measures include implantation rate (IR), clinical pregnancy rate (CPR), ongoing pregnancy rate/live birth rate (OPR/LBR), and miscarriage rate (MR). Odds ratios (ORs) were analyzed for pregnancy outcomes with a 95% confidence interval (CI). RESULTS:Nine articles were enrolled in this study. Patients receiving oral antibiotic administration (OAA) did not show any advantage over patients without CE with regard to IR, OPR/LBR, and MR, but they showed a higher CPR. Patients with cured CE after OAA therapy had significantly higher CPR, IR, and OPR/LBR compared with patients without CE. Patients with persistent CE after OAA therapy had significantly lower IR, CPR, and OPR/LBR compared with patients without CE. Patients with cured CE had significantly higher IR, CPR, and OPR/LBR compared with persistent CE patients. CONCLUSIONS:Antibiotic treatment may improve the pregnancy outcomes of RIF patients in subsequent IVF cycles only if the condition of CE is confirmed cured in a control biopsy afterwards. Otherwise, no sufficient evidence has shown improvements in clinical outcomes in RIF patients with persistent CE.

Objective: Several studies evaluated the relationship between estrogen receptor (ER) polymorphisms and the outcomes of controlled ovulation hyperstimulation (COH). However, the results remained obscure. The objective of this study was to perform a meta-analysis to investigate the links between ER polymorphisms and COH outcomes.Methods: Eligible studies were identified from the following electronic databases: PubMed, Embase and the Chinese CNKI till Nov. 2021. The odds ratio (OR) and 95% confidence intervals (CIs) for dichotomous data and the weighted mean difference (WMD) with 95% confidence intervals (CIs) for continuous variables were used to calculate correlations between ER polymorphisms and COH outcomes. Based on the inclusion and exclusion criteria, a total of thirteen papers were eventually enrolled in the current meta-analysis.Results: The following were the key findings of this meta-analysis: (1) PvuII polymorphism had a significant relationship with IVF pregnancy outcome in all models, except the recessive model(CC VS TT: OR, 5.51, 95% CI, 1.13,26.84; CC + CT VS TT: OR, 3.73, 95% CI, 1.21,11.57; CT VS TT: OR, 3.19, 95% CI, 1.11,9.16;C VS T: OR, 2.19, 95% CI, 1.15, 4.19), with large or extreme heterogeneity; (2) XbaI polymorphism had a significant association with IVF risk in heterozygous and dominant models(AG VS GG: OR, 0.27, 95% CI, 0.12,0.61; AAAG VS GG: OR, 0.27, 95% CI, 0.12,0.59), with no heterogeneity; (3) (TA)n polymorphism was linked with IVF risk in the homozygous and recessive models(LL VS SS:OR = 3.74, 95%CI = 1.53,9.12;LL VS LS + SS:OR = 2.75, 95%CI = 1.18, 6.38), with no heterogeneity; (4) for Alul polymorphism and its association with POR risk, significant relationship was observed in the recessive model(AA VS AG + GG:OR = 2.27, 95%CI = 1.46, 3.54), with no heterogeneity;(5) PvuII T/C mutation did not predict the follicle number, oocyte number, ratio of follicles to oocytes and the risk of IVF;(6) for XbaI polymorphism and pregnancy outcome of IVF, no significant association was observed under all models; and (7) RsaI polymorphism does not increase the risk of POR under all models.Conclusion: In summary, our meta-analysis found evidence supporting that PvuII polymorphism may serve as a marker in predicting pregnancy rate in IVF-ET, XbaI and (TA)n polymorphisms may be related with infertility, and Alul polymorphism may predict the poor ovarian response to COH. More well-designed investigations are warranted to corroborate these findings.

Developing female human germ cells undergo genome-wide epigenetic reprogramming, but de novo DNA methylation dynamics and their interplay with chromatin states and transcriptional activation in developing oocytes is poorly understood. Here, we developed a single-cell multi-omics sequencing method, scChaRM-seq, that enables simultaneous profiling of the DNA methylome, transcriptome, and chromatin accessibility in single human oocytes and ovarian somatic cells. We observed a global increase in DNA methylation during human oocyte growth that correlates with chromatin accessibility, whereas increases of DNA methylation at specific features were associated with active transcription. Integrated analyses of multi-omics data from humans and mice revealed species-specific gene expression, and promoter accessibility contributes to gene body methylation programs. Alu elements retained low DNA methylation levels and high accessibility in early growing oocytes and were located near developmental genes in humans and mice. Together, these findings show how scChaRM-seq can provide insight into DNA methylation pattern establishment.

Objective:To investigate the effects of pelvic floor neuromuscular electrical stimulation (PFNES) on endometrial thickness (ET), blood perfusion and pregnancy in patients with TE.Methods:A total of 96 outpatients with TE in the Department of Reproductive Medicine and Department of Reproductive Endocrinology, West China Second University Hospital, Sichuan University and had fertility needs from May 2016 to May 2018 were selected as research subjects. According to whether patients received PFNES therapy or not, they were divided into study group (n=51, received estrogen and PFNES therapy) and control group (n=45, only received estrogen therapy). ET, uterine artery pulsation index (PI), resistance index (RI), ratio of systolic to diastolic duration (S/D) before and after treatment in two groups were compared between groups and within groups by independent-samples t test and pairwise t test. Comparisons of spontaneous pregnancy rate and abortion rate between two groups were performed by chi-square test. All patients signed clinical research informed consents. This study was approved by the Ethics Committee of West China Second University Hospital, Sichuan University (Approved No.2015026). There were no statistical differences between two groups in age, years of infertility, basic estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH) levels, and ET, uterine artery PI, RI, S/D before treatment and other general clinical data (P>0.05).Results:①After treatment, ET of TE patients in study group was (9.2±1.1) mm, which was significantly higher than that before treatment (5.4±0.8) mm, and also significantly higher than that of control group (7.9±0.7) mm, and differences were statistically significant (t=6.327, 4.352, P all<0.001). ②After treatment, uterine artery PI, RI and S/D of TE patients in study group were (0.52±0.16), (0.23±0.06), and (2.05±0.29), respectively, which were significantly lower than those before treatment (0.89±0.23), (0.79±0.22), and (4.86±1.02), and also significantly lower than those of control group of (0.78±0.12), (0.67±0.14) and (3.92±1.02), and all differences were statistically significant (t=4.178, 6.743, 7.246, 6.583, 5.235, 5.932; P all<0.001). ③One year after treatment in two groups, spontaneous pregnancy rate of study group was 43.1% (22/51), which was significantly higher than that of control group 13.3% (6/45), and the difference was statistically significant (χ2=10.279, P=0.001); while there was no statistically significant difference in abortion rate between two groups (P>0.05).Conclusions:The treatment of PFNES can increase ET of TE patients, improve endometrial blood perfusion and receptivity, thus improving spontaneous pregnancy rate of patients.

Background: This study aims to compare the effect of tamoxifen (TMX) vs. other regimens on endometrial thickness (EMT), clinical pregnancy, implantation, miscarriage, and live birth rates in women with thin endometrium undergoing frozen-thawed embryo transfer (FET). Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and CINAHL from inception to November 2020 and cross-checked the references of relevant articles. We included randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs) to compare TMX with other regimens for endometrium preparation in women with thin endometrium undergoing FET. We pooled weighted mean differences (WMD) with 95% confidence intervals (CI) for continuous variables (EMT) and odds ratios (OR) with 95% CI for binary variables (i.e., clinical pregnancy rate, implantation rate, and first trimester miscarriage rate). Results: An RCT and three controlled trials (2 before-after and 1 retrospective controlled trials) were included in the final review. One study including 154 women and comparing TMX-FET with natural cycle (NC)—FET showed a significant increase in EMT in the TMX cycle (7.87 ± 1.48 mm vs. 6.11 ± 0.98 mm, P < 0.05). Three studies compared the EMT in the TMX and the hormone replacement treatment (HRT) cycles. The pooled analysis showed beneficial effect of TMX on EMT (WMD = 2.06, 95% CI = 1.86–2.27, P < 0.00001). An RCT and a retrospective controlled trial compared TMX and ovulation induction (OI) with Letrozole/human menopause gonadotropin (hMG) for endometrium preparation in women with thin endometrium undergoing FET. No significant difference in clinical pregnancy rates (OR = 1.03, 95% CI = 0.71–1.51), implantation rate (OR = 1.03, 95% CI = 0.76–1.38), or miscarriage rate (OR = 0.91, 95% CI = 0.40–2.06) was observed. No significant difference in EMT was found between TMX and OI with Letrozole/hMG in the included studies. Conclusions: In women with thin endometrium undergoing FET, the use of TMX may result in improved EMT than other regimens. At present, evidence supporting the preferred use of TMX over other regimens as clinical pregnancy rate, implantation rate, or the first trimester miscarriage rate is insufficient.

体外受精-胚胎移植(in vitro fertilization & embryo transfer,IVF-ET)技术作为帮助不孕不育夫妇获得后代的重要治疗手段,已经广泛应用于临床中.近十年,随着临床个体化控制性卵巢刺激(individual controlled ovarian stimulation,iCOS)方案等临床技术的改进、胚胎实验室培养体系的精准提高,使得在新鲜周期中可利用胚胎率提高,因此胚胎冷冻保存技术作为IVF衍生技术,已成为胚胎实验室不可或缺的基本技术.传统意义上,胚胎冻存技术的意义在于恰当保存一个周期内获得的多枚胚胎,通过冻融解冻移植,以提高一次取卵后患者的累积妊娠率,避免多次促排卵和取卵给患者带来的高额经济负担和身心伤害;同时也能通过全胚冷冻避免新鲜周期移植后部分高风险患者发生中重度卵巢过度刺激综合征(ovarian hyperstimulation syndrome,OHSS),提高临床技术的安全性.但随着冷冻-解冻的实验室技术的进步,特别是玻璃化冷冻(vitrification)代替了既往传统的程序化冷冻(慢速冷冻,slow freezing),使胚胎的复苏率提高,冷冻胚胎质量和解冻后发育、植入潜能的大幅提高,目前在国内外全胚冷冻周期率越来越高,产生了不同于传统的冷冻目的和意义的治疗方案.本文就全胚冷冻策略和胚胎解冻内膜准备方案某些新的观念做一介绍.

Background Unexplained recurrent spontaneous abortion (URSA) is defined as two or more consecutive pregnancy losses, generally of unknown cause; it is related to a failure of fetal–maternal immunological tolerance. Regulatory T cells (Tregs) exert immunosuppressive effects, which are essential to maintain fetal–maternal immunological tolerance and regulate immune balance. In this study, we used the specific cell-surface phenotype of CD4 + CD25 high CD127 low/− Tregs to investigate the number and suppressive function of Tregs isolated from the peripheral blood of patients with URSA with the aim of expanding our understanding of their role in URSA. Methods We isolated a relatively pure population of peripheral CD4 + CD25 high CD127 low/− Tregs and CD4 + CD25 − responder T cells (Tresps) from the patients with URSA and normal fertile nonpregnant control women via fluorescence-activated cell sorting. We compared the frequency, suppressive capacity, and forkhead box transcription factor P3 (FOXP3) expression of Tregs in the peripheral blood between patients with URSA and normal controls. Results The frequency of CD4 + CD25 high CD127 low/− Tregs in the peripheral blood was lower in URSA patients than in the controls ( P < 0.05). The mean fluorescence intensity of FOXP3 and FOXP3 mRNA expression in Tregs was also significantly lower in the URSA patients ( P < 0.01). Tregs suppressed the activity of autologous Tresps stimulated with anti-CD3/CD28 beads in a concentration-dependent manner, with the strongest suppression occurring in cocultures with a 1:1 Treg:Tresp ratio in both groups; however, patient-derived Tregs exhibited a poorer capacity to suppress the proliferation of autologous Tresps than the Tregs from normal controls ( P < 0.01). Moreover, Tregs isolated from URSA patients inhibited the proliferation of Tresps from normal controls less potently than the Tregs from normal controls ( P < 0.01), and Tresps from URSA patients were less effectively suppressed by autologous Tregs than by those from normal controls ( P < 0.01). Tresp activity were intact in both groups. Conclusions We observed a lower frequency of peripheral CD4 + CD25 high CD127 low/− Tregs with lower FOXP3 expression in the peripheral blood of URSA patients. In addition, highly purified Tregs from patients with URSA exhibited impaired suppressive effects. The defect in immune regulation in URSA patients appears to be primarily related to impaired Tregs, and not to increased resistance of Tresps to suppression. Our findings reveal a potential novel therapeutic target for URSA.

[目的]探讨白细胞介素 17 (IL-17 )在复发性流产(RSA)患者中的表达及其与抗心磷脂抗体(ACA)表达的相关性.[方法]选择 2016 年 12 月至2017 年 3 月在本院生殖门诊诊治的 35 岁以下RSA患者46 例,其中 ACA阳性患者 20 例(ACA阳性组),ACA阴性患者 26 例(对照组).采用 ELISA法检测患者血清中 IL-17 和 ACA的表达水平,并分析两者的相关性.[结果]ACA 阳性组患者血清 IL-17 水平为(41.9 ± 5.5)pg/mL,显著高于对照组的(32.1±4.3)pg/mL,其差异有统计学意义(P ＜0.05).Pearson相关性分析显示:RSA患者血清 IL-17 水平与 ACA表达呈正相关.[结论]外周血 IL-17 升高是 ACA阳性的 RSA患者的免疫异常之一,其可能参与了ACA导致流产的免疫机制.

BACKGROUND:Slow freezing has been widely applied to preserve human ovarian tissue. OBJECTIVE:The aim of this study is to determine whether human ovarian cortex pretreated with hyaluronidase can improve the protective effect of cryopreservation. MATERIALS AND METHODS:Human ovarian biopsies from seven patients were cryopreserved using slow freezing. The samples in the experimental group were incubated in culture medium with hyaluronidase for a short time before cryopreservation. The histology of the thawed ovarian tissue was investigated; the levels of steroid hormone in the culture media were then used to evaluate the development and function of thawed ovarian tissue. RESULTS:The result showed that the percentage of morphologically abnormal primordial follicles was higher in the freezing control than in the experimental group (P<0.05). 17β-estradiol (E2) and progesterone (P4) concentrations were significantly higher in the experimental group than in the freezing control group (P<0.05). CONCLUSION:Our study showed that human ovarian cortex pretreatment with hyaluronidase can improve the protective effect of cryopreservation by improving the penetration of cryoprotectant.

目的:研究人类白细胞抗原E(HLA-E)是否参与孕激素对JEG-3细胞VEGF基因表达的调节作用.方法:JEG-3细胞分为5组,接受不同处理:空白对照(组1)、孕激素处理(组2)、转染HLA-EsiRNA慢病毒后孕激素处理(组3),HLA-E siRNA慢病毒转染(组4)以及慢病毒阴性对照转染(组5).48小时后收集细胞,分别采用Real-time PCR和Western blot方法检测JEG-3细胞血管内皮生长因子(VEGF) mRNA及蛋白表达水平.结果:组2 JEG-3细胞的VEGF mRNA和蛋白表达较组1增高,差异有统计学意义(P＜0.05);沉默HLA-E基因(组4)导致VEGF mRNA和蛋白表达降低,与组1比较,差异有统计学意义(P＜0.05).组3 JEG-3细胞经HLA-E siRNA慢病毒转染、沉默HLA-E表达后再接受孕激素处理,VEGF mRNA及蛋白表达水平与组1比较差异无统计学意义(P＞0.05).组5与组1比较,VEGF mRNA及蛋白水平比较,差异无统计学意义(P＞0.05).结论:HLA-E介导孕激素对JEG-3滋养细胞VEGF表达的上调,孕激素对JEG-3细胞VEGF的上调作用被HLA-E基因的沉默消除.

Objectives: Focal Segmental Glomerulosclerosis (FSGS) is a progressive glomerular disease.The pathogenesis of this disease, however, remains unclear.Here, we attempted to identify key candidate genes in FSGS through stringent bioinformatic analysis. Methods:We systematically searched the Gene Expression Omnibus database for gene expression microarrays derived from human glomeruli tissues with FSGS.First, we identified differentially expressed genes (DEGs) by using the Limma package in R.Then, we subjected these DEGs to Gene Ontology (GO) analysis for further analysis.Finally, we constructed Protein-Protein Interaction networks (PPI) through four different methods and performed intersection analysis to further refine our results.Results: A total of 627 DEGs were identified between the FSGS and control groups, among which 534 were up-regulated and 93 were down-regulated.GO analysis revealed that the DEGs were enriched in mRNA processing, cell adhesion molecule binding, and cadherin binding.Furthermore, via PPI, 7 DEGs overlapped in the four groups constructed through different analytical approaches.We also validated the overlapped 7 hub genes in in vitro experiments, including RBM5 and HNRNPF, with potentially important roles in the development of FSGS. Conclusion:Our study provides a valuable resource for novel biomarkers and therapeutic targets for FSGS.

目的:检测复发性流产(RSA)患者血清维生素D(维生素D)水平并探讨其与D-二聚体(D-DI)表达的相关性.方法:回顾性分析179例(包括对照组49例、RSA组65例及不孕组65例)患者血浆总维生素D水平和D-DI水平.结果:RSA组和不孕组患者血浆维生素D水平低于对照组,差异有统计学意义(P＜0.05),但RSA组和不孕组两组患者间维生素D水平无显著性差异.RSA组血浆D-DI水平显著高于不孕组及对照组(P＜0.05);RSA组维生素D水平与D-DI呈负相关,但无统计学意义.结论:RSA患者及不孕患者中维生素D不足的比例较高;RSA组维生素D水平不足及其与之相关的血浆D-DI增高倾向,可能参与早期复发性流产的发生.

The human leucocyte antigen-G (HLA-G) 14-bp insertion/deletion polymorphism was implicated in recurrent implantation failure (RIF), but individual published studies showed inconclusive results. Thus, a meta-analysis was performed to clarify the effect of HLA-G 14-bp polymorphism on RIF risk.

Transforming growth factor (TGF)-beta 1 is involved invasion of human trophoblasts. However, the underlying mechanisms remain unclear. In this study, we performed Transwell assay and found that TGF-beta 1 promoted the invasion of trophoblast cell line JEG-3. Treatment with TGF-beta 1 up-regulated the expression of receptor-regulated Smad transcription factors Smad2 and Smad3, and two invasive-associated genes, namely, matrix metallopeptidase (MMP)-9 and MMP-2, in JEG-3 cells. Over-expressing activin receptor-like kinase (ALK) 5, the TGF-a type I receptor (T beta RI) enhanced the up-regulation of Smad2, Smad3, MMP-9, and MMP-2 induced by TGF-beta 1, whereas application of T beta RI inhibitor SB431542 diminished the stimulatory effects of TGF-beta 1 on these genes. Furthermore, transfection of Smad3 and ALK-5 seperately or in combination into JEG-3 cells before TGF-beta 1 treatment significantly increased the expression of MMP-9 and MMP-2. By contrast, silencing Smad3 and Smad2 by siRNAs significantly decreased the expression of MMP-9 and MMP-2, with Smad3 silence having a more potent inhibitory effect. Inhibiting TaRI with SB431542 or knockdown of Smad3, but not Smad2, abolished the stimulatory effect of TGF-beta 1 on the invasion of JEG-3 cells. Taken together, the results indicate that TGF-beta 1 activates the Smads signaling pathway in JEG-3 trophoblast cells and Smad3 play a key role in TGF-beta 1-induced invasion of JEG3 and up-regulation of MMP-9 and MMP-2 expression.