Untargeted metabolomics analysis reveals the metabolic disturbances and exacerbation of oxidative stress in recurrent spontaneous abortion.

BACKGROUND: Recurrent spontaneous abortion (RSA) is characterized by the occurrence of two or more consecutive spontaneous abortions, with a rising prevalence among pregnant women and significant implications for their physical and mental well-being. The multifaceted etiology of RSA has posed challenges in unraveling the molecular mechanisms underlying that underlie its pathogenesis. Oxidative stress and immune response have been identified as pivotal factors in the development of its condition. METHODS: Eleven serum samples from healthy pregnant women and 17 from RSA were subjected to liquid chromatography/mass spectrometry (LC-MS) analysis. Multivariate statistical analysis was employed to excavate system-level characterization of the serum metabolome. The measurement of seven oxidative stress products, namely superoxide dismutase (SOD), catalase (CAT), malonaldehyde (MDA), glutathione (GPx), glutathione peroxidase (GSH), oxidized glutathione (GSSG), heme oxygenase (HO-1), was carried out using ELISA. RESULTS: Through the monitoring of metabolic and lipid alternations during RSA events, we have identified 816 biomarkers that were implicated in various metabolic pathways, including glutathione metabolism, phosphonate and phosphinate metabolism, nucleotide metabolism, sphingolipid metabolism, lysine degradation and purine metabolism, etc. These pathways have been found to be closely associated with the progression of the disease. Our finding indicated that the levels of MDA and HO-1 were elevated in the RSA group compared to the control group, whereas SOD, CAT and GPx exhibited a contrary pattern. However, no slight difference was observed in GSH and GSSG levels between the RSA group and the control group. CONCLUSION: The manifestation of RSA elicited discernible temporal alternations in the serum metabolome and biochemical markers linked to the metabolic pathways of oxidative stress and immune response. Our investigation furnished a more comprehensive analytical framework encompassing metabolites and enzymes associated with oxidative stress. This inquiry furnished a more nuanced comprehension of the pathogenesis of RSA and established the ground work for prognostication and prophylaxis.

Expression and mechanism of micro-ribonucleic acid-29a in chorionic villi obtained at curettage with recurrent abortion.

Objective: Explored the expression of miR-29a in puerpera with RSA and its influencing mechanism. Method: 52 patients with RSA group were divided into 30 cases representing ≤3 abortions and 22 cases with ≥4 abortions,thirty healthy women who had induced abortion during the same period as the control group. The differences in the expression levels of miR-29a, FKBP52 mRNA, VEGF, MVD, and HIF-lα were compared between the groups by conducting a correlation analysis. Results: The expression levels of miR-29a, VEGF, MVD, and HIF-lα in the chorionic villus were significantly higher among patients in the group with ≥4 abortions than in those in the group with ≤3 abortions (P < 0.05), and the expression levels of FKBP52 mRNA were lower in the former than in the latter (P < 0.05). A Spearman correlation analysis revealed that the expression levels of miR-29a were positively correlated with the levels of VEGF, MVD, and HIF-lα (P < 0.05) and negatively correlated with the expression level of FKBP52 mRNA (P < 0.05). Conclusion: MiR-29a may be involved in the pathogenesis of RSA by inhibiting the protein expressions of FKBP52 and VEGF, promoting the apoptosis of trophoblasts, and impairing neovascularization, resulting in placental vascular dysplasia..

Amniocentesis and Next Generation Sequencing (NGS)-Based Noninvasive Prenatal DNA Testing (NIPT) for Prenatal Diagnosis of Fetal Chromosomal Disorders.

OBJECTIVE: The present study aimed to evaluate and analyze the results of karyotyping by amniocentesis and next generation sequencing (NGS)-based noninvasive prenatal DNA testing (NIPT) for the prenatal diagnosis of fetal chromosomal disorders. METHODS: A total of 2267 high-risk pregnant females with the indications for prenatal diagnosis who met the enrollment criteria between January 2015 and May 2019 at the Affiliated Hospital of Inner Mongolia Medical University were included and underwent NGS-based NIPT in the present study. Amniocentesis, chromosome karyotyping by cell culture, and follow-up of the pregnancy outcomes were also conducted in the NIPT-positive pregnant females to assess the consistency between NIPT and results of karyotyping by amniocentesis. RESULTS: Among the 2267 cases, 29 cases were positive for NIPT, including 10 cases with a high risk of trisomy 21, 2 cases with a high risk of trisomy 18, 2 cases with a high risk of chromosome 13, and 20 cases with sex chromosome abnormalities. All the above NIPT-positive cases underwent amniocentesis, and 20 cases were eventually diagnosed. The sensitivity and specificity of NIPT for the diagnosis of trisomy 21, trisomy 13, and trisomy 18 were 100%, 99.96%, 100%, and 99.96%, 100%, 100%, respectively, and the positive predictive values were 91.67%, 66.67%, and 100%, respectively. CONCLUSION: NGS of the fetal free DNA from the peripheral blood of pregnant females was an important complement to the prenatal diagnosis of chromosomal disorders represented by fetal chromosome aneuploidy with high sensitivity and specificity. In combination with the traditional karyotyping by amniocentesis, it could improve the diagnostic efficacy for fetal chromosomal disorders.