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Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in women of childbearing age. Recent studies suggest important roles for lncRNAs in PCOS development. Based on the hypothesis that lncRNAs are able to regulate mRNA functions by competitive binding to shared miRNAs, the present work sought to construct a PCOS-related lncRNA-mRNA network (PCLMN) to identify key lncRNAs with dysregulated expression and potential prognostic and therapeutic relevance. A global background network was constructed after retrieving lncRNA-miRNA and miRNA-mRNA pairs from the lncRNASNP2, miRTarBase and StarBase databases. Based on gene expression profiles from ovarian granulosa cells from PCOS patients and controls in the GEO’s GSE95728 dataset, the PCLMN was then constructed by applying hypergeometric testing. Using topological analysis, we identified 3 lncRNAs (LINC00667, AC073172.1 and H19) ranking within the top-ten gene lists for all three centrality measures. We then explored their subcellular localization, performed functional module analyses, and identified 4 sex hormone-related transcription factors as potential regulators of their expression. Significant associations with inflammation, oxidative stress, and apoptosis-related processes and pathways were revealed for the key lncRNAs in our PCMLN. Further studies verifying the mRNA/lncRNA relationships identified herein are needed to clarify their clinical significance.

BackgroundSubchorionic hematoma (SCH) is common in early pregnancy achieved by in vitro fertilization-embryo transfer/frozen embryo transfer (IVF-ET/FET), and is associated with adverse obstetric outcomes. However, there are no methods known to accurately predict the occurrence of SCH.ObjectiveTo establish a nomogram prediction model for predicting the risk of SCH in early pregnancy with IVF-ET/FET and to analyze pregnancy outcomes of patients with SCH.MethodsPatients who underwent IVF-ET/FET treatment and were diagnosed with clinical pregnancy were enrolled in our study. A total of 256 patients with SCH were enrolled in the SCH group, and 526 patients without SCH in the control group. Logistic regression was used to screen risk factors for SCH, and the nomogram was developed according to the regression coefficient of relevant variables. Discrimination, effect, calibration, and the predictive model’s clinical usefulness were assessed using the C-index, the area under the receiver operating characteristic standard curve, calibration plot, and decision curve analysis. Internal validation was assessed using bootstrapping validation. The effects of SCH on pregnancy outcomes were analyzed.ResultsA multivariate logistic regression analysis showed that fresh embryo transfer, polycystic ovary syndrome, hydrosalpinx, and thin endometrium were risk factors affecting the occurrence of SCH. Based on the above factors, a predictive model for the risk of SCH was created. The model displayed good discrimination, with a C-index of 0.783 (95% confidence interval: 0.750–0.816), area under the receiver operating characteristic standard curve of 0.783, and good calibration. A high C-index value of 0.765 could still be reached in the interval validation. Decision curve analysis showed that the nomogram was clinically useful when the intervention was decided at the SCH possibility threshold of 4%–87%. For patients with successful deliveries, the occurrence of SCH did not influence the gestational weeks of delivery, mode of delivery, preterm birth, height, and weight of the newborn.ConclusionWe screened the risk factors for SCH in patients who underwent IVF-ET/FET treatment. Successful establishment of a nomogram can effectively predict the occurrence of SCH. Furthermore, the incidence of miscarriage is higher in patients with SCH.

Background Studies have shown that abnormalities in the decidualization process were closely related to recurrent implantation failure (RIF). Prokineticin 2 (PK2) is a secreted protein with angiogenic and tissue remodeling functions but its role in the endometrium is unknown. Methods PK2 levels and its receptor PKR1 mRNA and protein levels in mid-secretory endometrium from normal and RIF women were examined by real-time PCR and western blotting, respectively. The effects of PK2 were evaluated by overexpressed PK2 in immortalized endometrial T-HESC cells using lentivirus vector and found different expression of Matrix metalloproteinase 9(MMP9) and lncRNA LUCAT1 by RNA-sequencing. The ability of PK2 to regulate LUCAT1 and MMP9 was verified in endometrial cells by real-time PCR and western blotting. Results Using endometrial biopsies from normal and RIF patients, we found increased expression of PK2, together with its receptor PKR1 in RIF patients. We then overexpressed PK2 in immortalized endometrial T-HESC cells using lentivirus vector and found decreased expression of Matrix metalloproteinase 9(MMP9), and increased expression of lncRNA LUCAT1. We verified the ability of PK2 to stimulate LUCAT1 and decrease MMP9 in endometrial cells. We further demonstrated that increased expression of a long noncoding RNA LUCAT1 and decreased expression of MMP9 in endometrial biopsies of patients with RIF. Thus, we highlighted the important role of PK2 and its receptor PKR1 in decidualization and RIF. Conclusion Prokineticin 2 and its receptor are important in endometrium decidualization. PK2 may affect endometrial decidualization through the LUCAT1- MMP9 pathway, thereby affecting embryo implantation.