Reproductive disorders, including intrauterine adhesion (IUA), premature ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS), are great threats to female reproduction. Recently, mesenchymal stem cells derived–extracellular vesicles (MSC-EVs) have presented their potentials to cure these diseases, not only for the propensity ability they stemmed from the parent cells, but also for the higher biology stability and lower immunogenicity, compared to MSCs. EVs are lipid bilayer complexes, functional as mediators by transferring multiple molecules to recipient cells, such as proteins, microRNAs, lipids, and cytokines. EVs appeared to have a therapeutic effect on the female reproductive disorder, such as repairing injured endometrium, suppressing fibrosis of endometrium, regulating immunity and anti-inflammatory, and repressing apoptosis of granulosa cells (GCs) in ovaries. Although the underlying mechanisms of MSC-EVs have reached a consensus, several theories have been proposed, including promoting angiogenesis, regulating immunity, and reducing oxidate stress levels. In the current study, we summarized the current knowledge of functions of MSC-EVs on IUA, POI, and PCOS. Given the great potentials of MSC-EVs on reproductive health, the critical issues discussed will guide new insights in this rapidly expanding field.

The endometrium thickness increases by which endometrial angiogenesis occurs in parallel with the rapid growth of endometrium during the proliferative phase, which is orchestrated by complex cell–cell interactions and cytokine networks. However, the intercellular communication has not been fully delineated. In the present work, we studied the cell–cell interactome among cells of human proliferative phase endometrium using single-cell transcriptomics. The transcriptomes of 33,240 primary endometrial cells were profiled at single-cell resolution. CellChat was used to infer the cell–cell interactome by assessing the gene expression of receptor–ligand pairs across cell types. In total, nine cell types and 88 functionally related signaling pathways were found. Among them, growth factors and angiogenic factor signaling pathways, including EGF, FGF, IGF, PDGF, TGFb, VEGF, ANGPT, and ANGPTL that are highly associated with endometrial growth, were further analyzed and verified. The results showed that stromal cells and proliferating stromal cells represented cell–cell interaction hubs with a large number of EGF, PDGF incoming signals, and FGF outgoing signals. Endothelial cells exhibited cell–cell interaction hubs with a plenty of VEGF, TGFb incoming signals, and ANGPT outgoing signals. Unciliated epithelial cells, ciliated epithelial cells, and macrophages exhibited cell–cell interaction hubs with substantial EGF outgoing signals. Ciliated epithelial cells represented cell–cell interaction hubs with a large number of IGF and TGFb incoming signals. Smooth muscle cells represented lots of PDGF incoming signals and ANGPT and ANGPTL outgoing signals. This study deconvoluted complex intercellular communications at the single-cell level and predicted meaningful biological discoveries, which deepened the understanding of communications among endometrial cells.

BackgroundThin endometrium on ovulation triggering day is associated with impaired pregnancy outcomes in women after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), but the role of thick endometrium on pregnancy outcomes remains controversial. Moreover, there has been insufficient evidence currently to analyze the influence of endometrial thickness (EMT) on obstetric complications and perinatal outcomes. Thus, we performed this meta-analysis to evaluate the effect of EMT on pregnancy, maternal, and perinatal outcomes in an enlarged sample size.MethodsThe databases Pubmed, Embase, Cochrane Libraries, and Web of Science were searched for English articles evaluating the correlation between EMT and pregnancy, maternal, or perinatal outcomes in women who underwent IVF/ICSI. We included studies that depicted a clear definition of outcomes and EMT grouping on ovulation triggering day. The EMT effect was analyzed in fresh cycle. Qualities of studies were assessed by the Newcastle-Ottawa Scale (NOS). Odds ratios (ORs) and weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated for analyzing dichotomous and continuous outcomes respectively, under a fixed or random effect model.ResultsA total of 22 pieces of literature were included for the final meta-analysis. A decreased trend towards pregnancy outcomes was observed, such as live birth rate (LBR), clinical pregnancy rate (CPR), and implantation rate (IR) in the thin endometrium groups (EMT <7 mm). In contrast, thick endometrium (EMT >14 mm) had no effect on pregnancy outcomes compared to medium EMT groups (EMT 7–14 mm). Moreover, thin endometrium (EMT <7.5 mm) enhanced the incidence of hypertensive disorders of pregnancy (HDP) and small-for-gestational-age (SGA) infants, and decreased the birthweight (BW) of babies.ConclusionsOur studies indicated that thin endometrium not only had detrimental effect on pregnancy outcomes, but also increased the risk of HDP in women and SGA of babies, or decreased BW of babies. The thick endometrium does not have an adverse effect on IVF outcomes. Therefore, patients need to be informed on possible obstetric complications and perinatal outcomes caused by thin endometrium and are encouraged to actively cooperate with perinatal care.Systematic Review Registration(https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=242637), identifier CRD42021242637.