Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves embryo implantation in mice by regulating local Treg/Th17 cell balance.

Immune imbalance of Treg/Th17 cells may contribute to recurrent implantation failure (RIF) during in vitro fertilization and embryo transfer (IVF-ET). In this study, we sought to determine the effect of intrauterine administration of mouse PBMCs prior to embryo implantation on endometrial receptivity and embryo implantation, and examine the underlying mechanism of Treg/Th17 cell balance following intrauterine administration of PBMCs. Pregnant mice were randomly divided into three groups: control group, embryo implantation dysfunction (EID) group, and EID with PBMCs group, and the number of embryo implantation sites was recorded during early pregnancy (Pd7.5). The balance of Treg/Th17 cells in the peripheral blood, spleen, and local implantation sites was detected during the peri-implantation period (Pd4.0) and early pregnancy (Pd7.5). The EID group demonstrated a significant decrease in the number of embryo implantation sites, while the EID with PBMCs group demonstrated higher number of embryo implantation sites compared to the EID group. The balance of Treg/Th17 cells in the peripheral blood and spleen tissues was not significantly different between the aforementioned groups. However, the local uterine ratio of the Treg/Th17 cells increased in the EID with PBMCs group compared to that in the EID group. Collectively, we found that intrauterine administration of PBMCs prior to embryo implantation effectively promotes embryo implantation rates. This may be attributed to the improvement in the local immune balance of Treg and Th17 cells compared with the overall immune balance.

Stromal-Cell-Derived Factor (SDF) 1-Alpha Overexpression Promotes Bone Regeneration by Osteogenesis and Angiogenesis in Osteonecrosis of the Femoral Head.

BACKGROUND/AIMS: Osteonecrosis of the femoral head (ONFH) is a devastating orthopedic disease. Previous studies suggested that stromal-cell-derived factor (SDF)-1 was involved in osteogenesis and angiogenesis. However, whether SDF-1 potentiates the angiogenesis and osteogenesis of bone marrow-derived stromal stem cells (BMSCs) in ONFH is not clear. METHODS: BMSCs were transfected with green fluorescent protein (GFP) or the fusion gene encoding GFP and SDF-1α, and transgenic efficacy was monitored by immunofluorescence. The expression of SDF-1α, runt-related transcription factor 2 (Runx2, osteocalcin (OCN), and alkaline phosphatase (ALP) at the mRNA level was measured by real-time polymerase chain reactions (RT-PCR). The expression of SDF-1α, Runx2, OCN, and p-Smad1/5 were measured at the protein level by Western blot. Transwell migration assay and tube formation assay were utilized to detect the angiogenesis in vitro, whereas the in vivo angiogenesis was monitored by angiography. Immunohistological staining and micro-CT scanning were conducted to assess the histological changes in morphology. RESULTS: In vitro, SDF-1α overexpression in BMSCs promoted osteogenic differentiation and upregulated the expression of osteogenic-related proteins, such as ALP, Runx2, OCN, and p-Smadl/5. In the methylprednisolone induced ONFH rat model used in our investigation, the overexpression of SDF-1α in BMSCs promoted significantly more bone regeneration and the expression of OCN and Runx2 as compared with the effect of vehicle overexpression. Moreover, the morphology of ONFH was ameliorated after the transplantation of BMSCs with SDF-1α overexpression. Furthermore, SDF-1α overexpression in BMSCs significantly increased osteoblastic angiogenesis as indicated by the increased tube formation ability, CD31 expression, and vessel volume. CONCLUSION: SDF-1α overexpression in BMSCs promotes bone generation as indicated by osteogenesis and angiogenesis, suggesting SDF-1α may serve as a therapeutic drug target for ONFH treatment.

Integrated analysis of multiple microarray studies to identify novel gene signatures in preeclampsia.

INTRODUCTION: Preeclampsia (PE) is one of the major causes of maternal and fetal morbidity and mortality in pregnancy worldwide. However, the intrinsic molecular mechanisms underlying the pathogenesis of PE have not yet been fully elucidated. METHODS: Robust rank aggregation (RRA), weighted correlation network analysis (WGCNA) and protein-protein interaction (PPI) methods were used to identify robust differentially expressed genes (DEGs) and hub genes in preeclampsia and subgroups based on 10 Gene Expression Omnibus (GEO) datasets. Subsequently, enrichment analysis and correlation analysis were performed to explore the potential function of the robust DEGs and hub genes. The diagnostic role of hub genes was further investigated by GSE12767. The miRNA regulators and the effect of hypoxia on hub genes were explored by using GSE84260 and GSE65271, respectively. RESULTS: Robust DEGs were identified in each subgroup including preeclampsia. Totally, 24 hub genes enriched in inflammatory response, renin-angiotensin system and JAK-STAT pathway, and 24 related miRNA regulators were identified. DISCUSSION: Our integrated analysis identified novel gene signatures in preeclampsia and subgroups and will contribute to the understanding of comprehensive molecular changes in preeclampsia.

Identification of potential crucial genes associated with early-onset preeclampsia via bioinformatic analysis.

INTRODUCTION: Early-onset preeclampsia is a pregnancy complication associated with high maternal and perinatal morbidity, mortality. Intense efforts have been made to elucidate the pathogenesis, but the molecular mechanism is still elusive. This study aimed to identify potential key genes related to early-onset preeclampsia, and to obtain a better understanding of the molecular mechanisms of this disease. METHODS: We performed a multi-step integrative bioinformatics analysis of microarray dataset GSE74341 downloaded from Gene Expression Omnibus (GEO) database including 7 early-onset preeclampsia and 5 gestational age matched normotensive controls. The differentially expressed genes (DEGs) were identified using the "limma" package, and their potential functions were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Furthermore, the protein-protein interaction network (PPI) was obtained from the STRING database and the PPI network was visualized by Cytoscape software. Then, hub modules and hub genes were screened out from the PPI network, and enrichment analysis was performed for them. Also, validation of hub genes expression in early-onset PE was down by using microarray dataset GSE44711. RESULTS: A total of 628 DEGs (256 down- and 372 up-regulated) were identified in early-onset PE compared to controls. A total of 4 significant hub modules and 26 significant hub genes were identified. CONCLUSION: In conclusion, the DEGs related to cell-cell or cell-extracellular matrix interaction (ITGA5, SPP1, LUM, VCAN, APP), placenta metabolic or oxidative stress (CCR7, NT5E, CYBB) were predicted to be newly potential crucial genes that may play significant roles in the pathogenesis of early-onset PE.

Predictive role of neutrophil-to-lymphocyte ratio in preeclampsia: A meta-analysis including 3982 patients.

OBJECTIVE: The predictive role of neutrophil-to-lymphocyte ratio (NLR) for preeclampsia (PE) has been explored in several studies and current evidence seems to be conflicting. The aim of this study is to compare the NLR values of mild and severe preeclampsia with the normotensive pregnant women, in order to explore the predictive role of NLR for preeclampsia and whether the NLR value has significant difference between severe and mild preeclampsia. DESIGN AND METHODS: We systematically searched Pubmed, Embase, Web of Science and Cochrane database for relative literature up to May 2019. The statistical analysis was performed using Stata 12.0 software. RESULTS: Totally 15 eligible studies consisting of 3982 patients were enrolled in our meta-analysis. The NLR value is higher in preeclampsia when compared to healthy pregnant women (3270 women, MD: 1.44, 95% CI [1.04, 1.83]). Furthermore, NLR value is higher in severe preeclampsia than in mild preeclampsia (1287 women, MD: 1.12, 95% CI [0.69,1.56]). CONCLUSIONS: The findings of our meta-analysis suggest that NLR value is higher in preeclampsia patients especially in severe preeclampsia. The NLR might be a useful laboratory marker for clinical prediction and disease severity evaluation of preeclampsia. However, given that the available evidence is mainly drawn from case-control studies, future cohorts are needed in this field to accurately determine optimal timing and cut-off values that may be used in the clinical setting.

Clinical manifestations and maternal and perinatal outcomes with COVID-19.

Coronavirus disease 2019 (COVID-19) is a novel type of highly contagious pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the COVID-19 outbreak unfolds, more and more pregnant women are infected with SARS-CoV-2, concerns have been raised about its clinical manifestations in pregnancy and the potential risk of vertical transmission from mother to fetus in pregnant women. Hence, in this review, we summarize the latest research progress related to COVID-19 epidemiology and the reported data of pregnant women with COVID-19 and discuss the clinical manifestations, treatments, maternal and perinatal outcomes, and intrauterine vertical transmission potential of such virus. Reported data suggest that symptoms in pregnant women are similar to those in other populations and that there is no evidence of vertical transmission from mother to child. In the meantime, considering the good prognosis of most of the infected mothers and infants and absence of serious obstetric complications in pregnant women with COVID-19, it is not recommended to give birth as soon as possible, and it is necessary to extend the gestational period reasonably.

Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study.

BACKGROUND: In December, 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. The number of affected pregnant women is increasing, but scarce information is available about the clinical features of COVID-19 in pregnancy. This study aimed to clarify the clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19. METHODS: In this retrospective, single-centre study, we included all pregnant women with COVID-19 who were admitted to Tongji Hospital in Wuhan, China. Clinical features, treatments, and maternal and fetal outcomes were assessed. FINDINGS: Seven patients, admitted to Tongji Hospital from Jan 1, to Feb 8, 2020, were included in our study. The mean age of the patients was 32 years (range 29-34 years) and the mean gestational age was 39 weeks plus 1 day (range 37 weeks to 41 weeks plus 2 days). Clinical manifestations were fever (six [86%] patients), cough (one [14%] patient), shortness of breath (one [14%] patient), and diarrhoea (one [14%] patient). All the patients had caesarean section within 3 days of clinical presentation with an average gestational age of 39 weeks plus 2 days. The final date of follow-up was Feb 12, 2020. The outcomes of the pregnant women and neonates were good. Three neonates were tested for SARS-CoV-2 and one neonate was infected with SARS-CoV-2 36 h after birth. INTERPRETATION: The maternal, fetal, and neonatal outcomes of patients who were infected in late pregnancy appeared very good, and these outcomes were achieved with intensive, active management that might be the best practice in the absence of more robust data. The clinical characteristics of these patients with COVID-19 during pregnancy were similar to those of non-pregnant adults with COVID-19 that have been reported in the literature. FUNDING: National Natural Science Foundation of China, Hubei Provincial Natural Science Foundation of China.

Risk Factors and Pregnancy Outcomes: Complete versus Incomplete Placenta Previa in Mid-pregnancy.

This prospective study was conducted to compare risk factors and pregnancy outcomes between women with complete placenta previa and those with incomplete placenta previa diagnosed in mid-pregnancy. The study was carried out from April 2014 to December 2015, during which 70 patients with complete previa and 113 with incomplete previa between 20+0 weeks and 25+6 weeks of gestation were included. Maternal demographics and pregnancy outcomes were compared between the two groups. Comparisons between categorical variables were tested by chi-squared test and those between continuous variables by Student t test. Resolution of previa occurred in 87.43% of the studied women. The mean gestational age at resolution was 32.1±4.4 weeks. Incidence of maternal age ≥35 years and incidence of prior uterine operation ≥3 were high in women with complete previa (28.6% vs 8.8%, P=0.003; 28.6% vs. 8.8%, P=0.003). Resolution of previa occurred less often in complete previa group (74.3% vs. 95.6%, P=0.001). Women with complete previa admitted earlier (37.3±2.0 weeks 38.1±1.4 weeks, P=0.011) and delivered earlier (37.7±1.2 weeks vs. 38.3±1.4 weeks, P=0.025). Maternal age ≥35 years and prior uterine operation ≥3 increase the risk of complete previa in mid-pregnancy. Placenta previa is more likely to persist in women with complete previa than those with incomplete previa diagnosed in midpregnancy. What is more, women with complete previa in mid-pregnancy delivers earlier.