Recurrent spontaneous abortion (RSA) presents a significant reproductive hurdle, impacting 2–5
Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies, largely due to its poorly understood pathogenesis, which limits the development of effective early detection and targeted therapy. This study was designed to explore the potential role of the long non-coding RNA CDIPTOSP in OC progression. We observed high expression of CDIPTOSP in OC tissues and cell lines. Knockdown of CDIPTOSP impeded the proliferation and migration of OC cells. Using the RNA pull-down-Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) approach, we found that CDIPTOSP bound staufen double-stranded RNA binding protein 1 (STAU1). In turn, CDIPTOSP-STAU1 interactions were essential for KLF transcription factor 17 (KLF17) mRNA destabilization. Notably, depletion of KLF17 could rescue the tumor-suppressive effects caused by CDIPTOSP knockdown, whereas overexpression of KLF17 abolished the tumor-promoting effects induced by overexpressing CDIPTOSP. In conclusion, our study provided the first evidence of the CDIPTOSP/STAU1/KLF17 axis in the regulation of OC progression.
Following the publication of the above article, an interested reader drew to the authors' attention that Figs. 3B and 4B contained western blot data (specifically, the MMP‑9 and Vimentin western blots in Figs. 3B and 4B, respectively) that were more similar than expected. Moreover, further strikingly similar data were also identified examining the western blot data within Fig. 4B and 4D, and also comparing the western blots in Figs. 1D, 3B, 4B and 4D with data featured in an article in the journal Oncotarget that was published subsequently to the above article, but which featured the first author (Pei Zhang) as an author in common. The authors were able to re‑examine their original data (which were also presented to the Editorial Office), and confirmed that the Vimentin data in Fig. 4B and the ZEB1 data in Fig. 4D were the same western bands as those featured for the MMP‑9 data in Fig. 3B and the Fibronectin data in Fig. 4B, respectively. These errors were made during the assembly of Fig. 4 (the data for MMP‑9 and Fibronectin were inadvertently duplicated in the figure). The corrected version of Fig. 4, now displaying the accurate experimental data for the Vimentin (Fig. 4B) and ZEB1 (Fig. 4D) blots in the CNE2Z and CNE2Z/DDP groups, is shown on the next page. Furthermore, regarding the issue of image duplication comparing between the above article published in 2014 and the one published in Oncotarget in 2015, the authors will contact the Oncotarget journal to handle the necessary corrections. The authors can confirm that the errors associated with this figure did not have any significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 33: 151‑159, 2014; DOI: 10.3892/ijmm.2013.1538].
This study investigates the role of phosphatidylethanolamine cytidylyltransferase 2 (PCYT2) in ovarian epithelial cancer, specifically examining its effects on cell migration and membrane fluidity. To achieve this, we will examine how the AMPK and FOXO1 pathways regulate these processes. Our analysis revealed a significant upregulation of PCYT2 expression in metastatic ovarian cancer tissues compared to primary cancer sites, which correlates with altered membrane fluidity. Our data indicate that PCYT2 is essential for modulating the invasive characteristics of ovarian cancer cells. It does this by regulating the expression levels of AMPK and FOXO1, suggesting its role as an upstream regulator in this signaling pathway. Experiments that either inhibit or enhance PCYT2 activity suggest that it may influence cancer cell infiltration by changing membrane fluidity. These findings provide valuable insights into the molecular mechanisms of ovarian cancer metastasis and highlight PCYT2 as a promising therapeutic target. Future research should validate these findings in larger cohort studies, and also explore the therapeutic potential of targeting PCYT2 in ovarian cancer treatment. In conclusion, although there have been substantial advancements in ovarian cancer therapies, the intricate nature of its metastatic behavior remains a major challenge. Our research clearly demonstrates the critical role of PCYT2, urging the scientific community to deepen their understanding of its involvement in cancer progression and to develop innovative treatment strategies.
BACKGROUND:Gasdermin D (GSDMD)-mediated pyroptosis drives inflammatory cytokine release in response to environmental triggers. Disulfiram (DSF), an FDA-approved anti-alcoholism drug, has been demonstrated to inhibit GSDMD pore formation. Although airway epithelial barrier dysfunction contributes to chronic obstructive pulmonary disease (COPD) progression, the role of GSDMD-dependent pyroptosis in ozone-induced pathogenesis, and the potential of DSF to inhibit this process, remain unexplored. METHODS:We analyzed the expression levels of pyroptosis-related molecules in airway epithelial cells from COPD patients' samples obtained from the Gene Expression Omnibus (GEO) database and evaluated the potential therapeutic effects of DSF in a mouse model of COPD induced by chronic ozone exposure. RESULTS:GSDMD was significantly upregulated in the airway epithelial cells of COPD patients. Chronic ozone exposure in mice elevated the cleaved form of GSDMD and reduced the expression of epithelial junctional proteins. DSF treatment effectively inhibited GSDMD-mediated pyroptosis and attenuated epithelial barrier disruption, leading to significant improvements in airway inflammation and lung function in both large and small airways. Furthermore, Gsdmd expression was negatively correlated with the tight junction protein Occludin and pulmonary function indices, including the ratio of FEV25 to FVC and MMEF. CONCLUSION:Collectively, these findings revealed the role of GSDMD-mediated pyroptosis in epithelial barrier disruption of COPD and the potential application of DSF in the treatment of COPD.
To review how DNA methylation affects ovarian steroidogenesis in polycystic ovary syndrome (PCOS), with evidence from human and animal studies. Women with PCOS show global DNA hypomethylation and altered methylation of ovarian steroidogenic genes, contributing to hyperandrogenism. Animal models of PCOS mirror these epigenetic changes and support a causal role, highlighting DNA methylation signatures as diagnostic biomarkers and therapeutic targets.
OBJECTIVE:To investigate the relationship between the trajectories of serum potassium changes after intensive care unit (ICU) admission and 30-day death risk in patients with sepsis. METHODS:A retrospective cohort study was conducted, including adult patients with sepsis admitted to the comprehensive ICU, medical intensive care unit (MICU) and emergency intensive care unit (EICU) of Guizhou Medical University Affiliated Hospital from January 2020 to January 2024. The patients who had a minimum of 5 days' hospitalisation in the ICU and who had at least 7 consecutive days of the serum potassium measurements were classified into five trajectories groups according to group-based trajectory modelling (GBTM) using SAS software. This was based on tendency changes in serum potassium levels in patients after admission to the ICU, which was categorized as follows: slowly increased from a low level group, slowly increased from a medium level of normal range group, slowly decreased from a medium level of normal range group, slowly decreased from a high level group, and slowly increased from a high level of normal range group. The patient's gender, age, medical history, and white blood cell count (WBC), platelet count (PLT), procalcitonin (PCT), activated partial thromboplastin time (APTT), prothrombin time (PT), blood sodium, and serum creatinine (SCr) at the time of admission to the ICU were collected. At the same time, the patient's worst sequential organ failure assessment (SOFA) score within 24 hours of admission to the ICU, length of ICU stay, and 30-day outcome were record. The differences in clinical data among different groups of patients were compared. The 30-day cumulative survival rates of the various serum potassium trajectories were plotted using Kaplan-Meier survival curves, the groups were then compared using the Log-Rank test. A multivariate Cox proportional risk regression analysis was developed to evaluate the independent effect of serum potassium trajectory on 30-day death risk. RESULTS:Finally, 342 ICU sepsis patients were enrolled, of which 42 patients in the slowly increased from a low level group (12.28%), 127 patients in the slowly increased from a medium level of normal range group (37.14%), 118 patients in the slowly decreased from a medium level of normal range group (34.50%), 28 patients in the slowly decreased from a high level group (8.19%), and 27 patients in the slowly increased from a high level of normal range group (7.89%). Except for age and APTT differences, there were no statistically significant differences in other clinical characteristics among the patients in the different serum potassium trajectories groups. Kaplan-Meier survival curves showed that there was statistically significant difference in the 30-day cumulative survival rate among the patients in the different serum potassium trajectories groups (Log-Rank test: χ2 = 14.696, P = 0.005), with the lowest in the slowly increased from a high level of normal range group (39.3%). Multivariate Cox proportional risk regression analysis showed that the patients with the serum potassium trajectory of slowly increased from a high level of normal range had the highest 30-day death risk [hazard ratio (HR) = 2.341, 95% confidence interval (95%CI) was 1.049-5.226, P = 0.038]. This association persisted after adjustment for variables such as gender, age, medical history, SOFA score, WBC, PLT, PCT, APTT, PT, blood sodium, and SCr (HR = 3.058, 95%CI was 1.249-7.488, P = 0.014). CONCLUSION:Compared with the patients whose serum potassium fluctuated within the normal range, the sepsis patients in the ICU with a serum potassium trajectory that slowly increased from a high level of normal range had a significantly higher 30-day death risk.
OBJECTIVE:To investigate the regulatory effect of glycyrrhizin (GL) on the release of neutrophil extracellular traps (NETs) from neutrophils in sepsis. METHODS:HL-60 cells were induced to differentiate into neutrophil-like dHL-60 cells to establish a neutrophil-like sepsis model. Expression levels of high-mobility group box 1 (HMGB1), citrullinated histone H3 (Cit-H3), and Toll-like receptor 9 (TLR9) were assessed by Western blotting. Free DNA, a component of NETs, was quantified using a fluorescence microplate reader. Cellular immunofluorescence analysis was used to detect the expression of the key NETs protein, Cit-H3. RESULTS:dHL-60 cells stimulated with 200 ng/ml LPS exhibited the highest expression of Cit-H3. The neutrophil-like sepsis model showed significantly increased levels of Cit-H3 and HMGB1. GL intervention significantly reduced the expression levels of HMGB1 and Cit-H3 and decreased the free DNA level. These findings suggest that GL decreases HMGB1 expression and NET release in the neutrophil-like sepsis model. TLR9 expression was significantly elevated in the sepsis model. Exogenous recombinant human HMGB1 protein further increased TLR9 expression, while GL inhibited this increase. CONCLUSION:GL may inhibit NET release in sepsis through the HMGB1/TLR9 pathway.
Background: F-box and leucine-rich repeat protein 18 (FBXL18) is an F-box protein that functions as an E3-ubiquitin ligase, and it plays pivotal roles in multiple disease processes. However, its role and underlying mechanism in ovarian cancer (OC) are still unknown. We investigated the impact and mechanism of FBXL18 in OC cell growth and tumorigenesis. Methods: Silent interfering RNAs and overexpression plasmids were employed to knock down and overexpress FBXL18 in OC cells (A2780 and OVCAR3). CCK-8, colony formation, cell migration, and nude mouse xenograft assays were used to assess the effect of FBXL18 on OC cell proliferation and migration. Western blotting and co-immunoprecipitation followed by ubiquitination assays were performed to detect the mechanism of the FBXL18/AKT axis in OC. Results: FBXL18 knockdown inhibited OC cell proliferation and migration, whereas FBXL18 overexpression showed the opposite results. Phosphorylated-AKT (S473) protein expression was increased by FBXL18 overexpression and markedly decreased after phosphorylated-AKT inhibitor (MK-2206) treatment. Coimmunoprecipitation assays demonstrated that FBXL18 strongly interacted with AKT in OC cells. Ubiquitination assays revealed that FBXL18 promoted K63-linked AKT ubiquitination to activate AKT. MK-2206 treatment reversed the increase in proliferation and migration of OC cells induced by FBXL18 overexpression. Conclusions: FBXL18 promoted OC cell proliferation and migration and facilitated OC tumorigenesis. Mechanically, FBXL18 interacted with AKT and promoted K63-linked ubiquitination of AKT to activate AKT in OC cells. Our study revealed that the FBXL18/AKT axis plays a crucial role in the OC process, indicating that FBXL18 may be a valuable target for OC diagnosis and treatment.
OBJECTIVE:To investigate the effects of different drug treatments on uterine artery blood flow parameters, serum placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and sFlt-1/PLGF in patients with recurrent spontaneous abortion and to explore the predictive value of uterine artery blood flow parameters, serum PLGF, sFlt-1, and sFlt-1/PLGF for pregnancy outcomes. METHODS:This retrospective cohort study included 173 patients who experienced recurrent spontaneous abortion and 100 control patients. Patients with recurrent spontaneous abortion were divided into an aspirin group (75 patients), aspirin combined with low molecular weight heparin (LMWH) group (68 patients), and non-drug group (30 patients) based on different drug treatments. Uterine artery blood flow parameters at gestational weeks 30-31+6 were monitored for the four groups, and serum samples were collected at gestational weeks 30-31+6 to measure the levels of serum PLGF and sFlt-1 and calculate the sFlt-1/PLGF ratio. RESULTS:1. Uterine artery blood flow parameters at gestational weeks 30-31+6 were significantly greater in the non-drug group than in the aspirin group, combined drug group, and control group (p<0.05). 2. Serum PLGF levels and the sFlt-1/PLGF ratio at gestational weeks 30-31+6 were significantly lower in the non-drug group than in the aspirin group, combined drug group, and control group, while serum sFlt-1 levels were significantly greater in the non-drug group than in the aspirin group, combined drug group, and control group (p<0.05). 3. Serum PLGF, sFlt-1, and sFlt-1/PLGF had lower diagnostic efficiency for predicting hypertensive disorders during pregnancy than the combined diagnostic efficiency of serum PLGF, sFlt-1, and sFlt-1/PLGF with uterine artery blood flow parameters at gestational weeks 30-31+6. CONCLUSION:Aspirin and aspirin combined with LMWH can upregulate serum PLGF and decrease serum sFlt-1 levels in patients with recurrent spontaneous abortion, reduce the miscarriage rate, and significantly improve pregnancy outcomes. The combination of serum PLGF, sFlt-1, sFlt-1/PLGF, and uterine artery blood flow parameters can effectively predict hypertensive disorders during pregnancy.
Abstract Objective to analyze the uterine artery and spiral artery blood flow parameters in patients with unexplained recurrent spontaneous abortion (URSA) with different pregnancy outcomes, to compare the predictive value of uterine artery and spiral artery blood flow parameters in pregnancy outcome, and to explore the possible mechanism of URSA and the effect of different drug regimens on pregnancy outcome in URSA patients. Methods a retrospective cohort study was conducted to analyze the clinical data of 174 pregnant women with unexplained recurrent abortion and 144 pregnant women without adverse pregnancy history. According to the pregnancy outcome, the pregnant women with unexplained recurrent abortion were divided into normal pregnancy outcome group (URSA-N,n = 138) and adverse pregnancy outcome group (URSA-A,n = 36). The pregnant women in the control group were divided into normal pregnancy outcome group (CON-N,n = 129) and adverse pregnancy outcome group (CON-A,n = 15). The blood flow parameters of uterine artery and spiral artery in mid-luteal phase, 11–13 weeks of gestation, 15–17 weeks of gestation and 19–21 weeks of gestation were compared, and the predictive value of uterine artery blood flow parameters and spiral artery blood flow parameters on pregnancy outcome was compared. the effects of aspirin and aspirin combined with low molecular weight heparin on pregnancy outcome in patients with unexplained recurrent abortion were evaluated. Results there was no significant difference in age and body mass index (BMI) between URSA group and CON group. The number of spontaneous abortion and BMI in URSA-N group were less than those in URSA-A group. There was no significant difference in age and BMI between CON groups. The spiral artery blood flow parameters of URSA-N group and CON-N group were lower than those of URSA-A group and CON-A group at mid-luteal phase, 11–13 weeks, 15–17 weeks and 19–21 weeks of gestation, respectively. The uterine artery blood flow parameters (mRI, mPI, mS/D) in the middle luteal period, uterine artery pulse index (mPI) at 11–13 weeks of gestation, peak systolic flow rate/diastolic (mS/D) flow rate at 15–17 weeks of gestation in URSA-N group were lower than those in URSA-A group, and the uterine artery blood flow parameters (mRI, mPI, mS/D) of the CON-N group were lower than those of the CON-A group at the middle luteal stage and weeks 11–13 of gestation. The area under the ROC curve of spiral artery blood flow parameters (mRI,mPI,mS/D) was larger than that of uterine artery. There were significant differences in the efficacy of different drugs between the URSA-N group and the URSA-A group, and aspirin combined with low molecular weight heparin could improve the pregnancy outcome.The area under the ROC curve of spiral artery blood flow parameters (mRI,mPI,mS/D) was larger than that of uterine artery. There were significant differences in pregnancy outcomes among different treatment schemes, and aspirin combined with low molecular weight heparin could improve the pregnancy outcome. The area under the ROC curve of spiral artery blood flow parameters (mRI,mPI,mS/D) was larger than that of uterine artery. There were significant differences in the efficacy of different drugs between the URSA-N group and the URSA-A group, and aspirin combined with low molecular weight heparin could improve the pregnancy outcome. Conclusion the blood flow parameters (mRI,mPI,mS/D) of uterine artery and spiral artery in adverse pregnancy outcome group are higher than those in normal pregnancy outcome group. Abnormal blood flow parameters of uterine artery and spiral artery may be one of the causes of URSA and adverse pregnancy outcome. Spiral artery blood flow parameters are more valuable than uterine artery blood flow parameters in predicting pregnancy outcome. Aspirin combined with low molecular weight heparin can improve the pregnancy outcome of URSA patients more than aspirin alone.
Overexpressed long noncoding RNA FTX is associated with low survival rate of epithelial ovarian cancer (EOC) patients, and enhances tumor infiltration. Thus, we aim to illuminate the undefined underlying mechanisms. Real-time quantitative polymerase chain reaction was applied to detect the expressions of FTX, miR-7515, miR-342-3p, miR-940, miR-150-5p, miR-205-5p and tumor protein D52 (TPD52). Cell counting kit-8 and transwell assays were utilized to explore the cell viability, migration or invasion of EOC cells. Western blot was conducted to measure the expressions of E-cadherin, N-cadherin, Met, phosphorylated (p)-Met, Akt, p-Akt, mTOR and p-mTOR. LncBase and TargetScan predicted the binding of miR-7515 with FTX, and the binding of TPD52 with miR-7515, respectively. The two bindings were further validated by dual luciferase reporter assay. As a result, FTX sponged miR-7515 and miR-7515 targeted to TPD52. FTX was overexpressed in four EOC cell lines. Overexpressed FTX enhanced the cell viability, migration or invasion of EOC cells, elevated N-cadherin and TPD52 expressions, phosphorylated Met/Akt/mTOR, and inhibited E-cadherin expression. All these influences were subsequently reversed by miR-7515 mimic. Collectively, FTX regulates miR-7515/TPD52 to facilitate the migration, invasion or epithelial-mesenchymal transition of EOC through activating Met/Akt/mTOR signaling pathway.
Objective: To explore the efficacy and feasibility of self-made negative pressure reflux system combined with rigid ureteroscopy in the treatment of upper ureteral calculi. Methods The clinical data of 379 Exercise-minded patients with upper ureteral calculi treated in our hospital from January 2018 to August 2022 were analyzed retrospectively. F8.0/9.8STORZ ureteroscope was used to explore the ureteral opening on the affected side, and then the 200 mu m wavelength holmium laser fiber and F4 ureteral catheter were inserted into the stone incarceration site through the rigid ureteroscope, and the residual stone fragments which were clinically meaningless (the maximum diameter of the stone < 2mm) were completely sucked out by negative pressure reflux system. Results A total of 379 Exercise- minded patients were included in this study, with a one-time success rate of 97.1% (368/379), aged 26 to 76 years, with an average of (47.5) years. Most of the Exercise-minded patients (63.2%) had low back pain and hematuria before operation. The average diameter of stone was 0.8cm similar to 2.8cm, the mean diameter of the stone was 1.8 +/- 1.0 cm.The operation time ranged from 18min to 52min, with an average of (37.86 +/- 25.64)min.The average length of hospital stay was (2.7 +/- 1.7) days (range, 1-8 days). On the first day after operation, the stone clearance rate was 84.43% (320/379), and the stone clearance rate was 90.77% (344/379) 3 months after operation. Among them, 4 Exercise-minded patients developed fever and 6 Exercise-minded patients had mild urinary fistula or renal pelvis perforation. Stone composition analysis was mainly ammonium phosphate stones and calcium oxalate stones. Conclusion The treatment of upper ureteral calculi with self-made negative pressure reflux system combined with hard ureteroscope has the advantages of high stone clearance rate, low complications and greatly reducing the utilization rate of soft lens,and had high clinical promotion value.
To analyze the uterine artery blood flow parameters of patients with recurrent spontaneous abortion (RSA) at different gestational ages and to investigate the effects of aspirin and low molecular weight heparin (LMWH) on uterine artery blood flow parameters and pregnancy outcomes.
Gonadotropin releasing hormone antagonist(Gn RH-A) directly inhibits gonadotropin(Gn) secretion by binding to gonadotropin releasing hormone(Gn RH) receptor competitively. Antagonists can be administered once or many times.Many clinical applications have been explored. Antagonists can combine with clomiphene, aromatase inhibitor or human menopausal gonadotropin and so on. Antagonist has been widely used because of its advantages such as reducing the occurrence of ovarian hyperstimulation syndrome, reducing the dosage of gonadotropin, and being suitable for a wide population. However it may lead to a low pregnancy rate in fresh cycle transplantation. This article aims to review the application and research progress of antagonists in assisted reproduction.
目的 比较三种不同子宫输卵管造影术后的临床妊娠率、妊娠间隔时间,探讨三种不同造影方法的适宜人群及使用节点.方法 根据纳入和排除标准,选取行三种子宫输卵管造影患者各200 例,其中双侧输卵管通畅患者共326 例(碘水HSG患者113 例,碘油HSG患者94 例,TVSRT-3DHyCoSy患者119 例).比较分析三种子宫输卵管造影术后6 个月内的临床妊娠率、早期流产率、异位妊娠率、多胎妊娠率及造影与妊娠时间间隔等指标.结果 三组患者年龄、不孕类型、平均月经间隔、不孕年限及盆腔手术史基本资料比较,差异均无统计学意义(P>0.05).碘水HSG组、碘油HSG组和TVSRT-3DHyCoSy组临床妊娠率分别为32.4%(35/108)、37.4%(34/91)、33.6%(38/113).碘油HSG组略高于TVSRT-3DHyCoSy 组,但三组间差异无统计学意义(P>0.05).三组早期流产率、异位妊娠率、双胎妊娠率差异无统计学意义(P>0.05).碘水HSG组平均妊娠时间间隔为3.99 个月,碘油HSG组为4.1 个月,TVSRT-3DHyCoSy组为2.89 个月,三组间差异有统计学意义,TVSRT-3DHyCoSy组术后平均妊娠时间最小(P<0.05).结论 三种子宫输卵管造影术后临床妊娠率、早期流产率、异位妊娠率和双胎妊娠率差异无统计学意义,但TVSRT-3DHyCoSy术可缩短手术与妊娠的时间间隔.
目的 探讨血清抑制素B(INHB)在促性腺激素释放激素拮抗剂(GnRH-A)方案中的动态变化及对体外受精-胚胎移植(IVF-ET)结局预测价值.方法 回顾性分析2018年10月-2020年9月于苏州大学附属第一医院生殖中心首次接受GnRH-A方案的81例患者临床资料,收集月经第2或3天(Db)、Gn第5或6天(DGn)、使用GnRH-A 2 d后(DGnRH-A)、HCG日(DHCG)的血清INHB水平.将38例行新鲜周期胚胎移植的患者分为ET妊娠组(n=17)和ET未妊娠组(n=21);将71例进行胚胎移植(新鲜周期和/或冷冻周期)的患者分为总妊娠组(n=40)和总未妊娠组(n=31).10例患者未行胚胎移植,其中4例患者无可移植胚胎,6例患者在观察期内因个人原因未行胚胎移植.观察INHB的动态变化及与IVF-ET结局参数的相关性,比较各妊娠分组中血清INHB水平.结果 Db、DGn、DGnRH-A、DHCG的血清INHB水平呈现先上升后下降的趋势,INHB与Gn用量存在明显负相关(P<0.05);与大中卵泡数(直径≥14 mm)、成熟卵泡数(直径≥18 mm)、DHCG-E2、获卵数、2PN受精卵数、2PN卵裂数及胚胎数存在正相关(P<0.05);均与优质胚胎数无明确相关性.ET妊娠组中DGnRH-A-INHB水平低于ET未妊娠组,总妊娠组和总未妊娠组INHB水平比较,差异无统计学意义(P>0.05).结论 在GnRH-A方案促排卵过程中,血清INHB水平呈现先上升后下降的动态变化,血清INHB水平对卵巢功能、卵母细胞及胚胎数量存在一定的预测价值,其中加入GnRH-A后的血清INHB水平对新鲜周期胚胎移植妊娠结局可能存在预测价值.
Prenatal hypoxia (PH) is a common feature of a suboptimal intrauterine environment affecting the development of fetuses. Whether PH leads to abnormal ovary development is not yet clear. This study investigated ovarian function in offspring exposed to PH and the potential underlying molecular mechanisms. SD female rats (n = 12 per group) at 9 weeks of age were housed in individual cages (21% O2). After the pregnant rats were exposed to hypoxia (10.5% oxygen) from embryonic day (E) 5 to E21, PH offspring were generated. All animals maintained normoxia during lactation. The number of follicles was counted in female offspring at 3 months under an optical microscope. The expression of Nobox, Gdf9, and Tets was detected by quantitative real-time polymerase chain reaction (PCR) and Western blot. Global DNA hydroxymethylation was measured by dot blot. The hydroxymethylation level of the Nobox gene was evaluated with an NGS-based multiple targeted CpG hydroxymethylation analysis method. Body weight and ovary weight were significantly decreased in the PH group compared with the control group. PH offspring have abnormal estrous cycle, decreased serum anti-Mullerian hormone (AMH), and increased serum follicle-stimulating hormone (FSH), and follicular atresia, which are consistent with the clinical manifestations in patients with ovarian dysfunction. In terms of mechanism, the expression of Nobox was significantly decreased in the PH group. Subsequent high-throughput sequencing results showed that the level of hydroxymethylation in the candidate region of the Nobox gene was reduced. Cultured cells treated with hypoxia exhibited lower levels of both 5hmC and Nobox, while vitamin C, a coactivator of Tets, rescued hypo-hydroxymethylation and increased the expression level of Nobox. This study indicated that PH could cause hypo-hydroxymethylation of Nobox through epigenetic regulation and may consequently contribute to ovarian dysfunction in adult rat offspring.
Several studies demonstrate that para-phenylenediamine (PPD) is often added to permanent oxidative hair dyes. Sub-chronic topical exposure to PPD in male rats damages their testicular function; however, little is known about the effects of PPD exposure on the female reproductive system, especially on oocyte quality. In this study, we found that PPD can affect the meiotic capacity of oocytes and their fertilization potential. In particular, PPD can damage the spindle/chromosome structure and prevent oocytes from developing and maturing normally. Furthermore, PPD exposure compromised the dynamics of cortical granules and their component, ovastacin. In addition to the protein level of Juno, the sperm receptors on the egg membrane, were substantially impaired in PPD-administered oocytes, thus leading to fertilization failure. Finally, we found that PPD exposure resulted in abnormal mitochondrial function, which led to oocyte degeneration, apoptosis, and increased ROS levels. Altogether, our study illustrates that mitochondrial dysfunction and redox perturbation are the major causes of the poor quality of oocytes exposed to PPD.
PROBLEM:To investigate how asymptomatic bacterial imbalance affects the clinical pregnancy rate after artificial insemination with the husband's semen (AIH).METHODS:This study included married heterosexual couples who underwent AIH. According to the follow-up results, participants were divided into the pregnancy and non-pregnancy groups. Based on the first 10 pair participants in each group with vaginal flora bacterial 16S rRNA sequencing results, six semen samples received bacterial-sperm mixed test. Moreover, 34 cytokines were detected in the peripheral blood sera of the first three pairs by high-throughput Luminex, which were verified in vaginal secretions, cervical mucus, and blood sera from the first 200 pairs by ELISA.RESULTS:The results of the 16S sequencing of vaginal secretions showed that compared with the pregnant group, the non-pregnant group had a significantly increased bacterial species diversity, which was mainly manifested by a decrease in Lactobacillus crispatus and an increase in Prevotella bivia. When Prevotella bivia or Lactobacillus crispatus were mixed with sperms, the sperm motility was decreased (p < .05). The vaginal posterior fornix secretions, cervical mucus, and peripheral blood sera of the non-pregnant group showed decreased levels of MIP-1α and increased levels of IL-17A (p < .05).CONCLUSION:The imbalance of vaginal flora leading to the increase of Prevotella bivia and the decrease of Lactobacillus crispatus may cause an imbalance of immune regulation. Low expression of MIP-1α and high expression of IL-17A were associated with reduced clinical pregnancy rate in AIH.