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Numerous studies have suggested the possibility of explaining the etiology of metabolic syndrome through DNA methylation. DNA methyltransferase 3B (DNMT3B) plays an important role in de novo DNA methylation. There was an alteration in maternal (F0) endometrial function, which might lead to growth and developmental disorder in offspring (F1). In this study, we investigated the effect of maternal endometrial DNMT3B deficiency on the metabolism in offspring. We constructed endometrial DNMT3B conditional knockout female mice (cKO) which were mated with normal C57BL/6 male mice to obtain the F1 generation. Further, to study the development of these offspring, we observed them at three different life stages which included the 6-week-old juvenile, 9-week-old sub-adult and 12-week-old adult. Follow the detection of a range of metabolism-related indicators, we found that in the cKO F1 generation, liver triglyceride level was significantly elevated in 9-week-old female mice, lipid droplet deposition was significantly increased in 9-week-old and 12-week-old mice, and the expression of lipid metabolism key factors in the liver was markedly decreased except of 6-week-old male mice. These results indicate that maternal endometrial DNMT3B conditional knockout leads to imbalance in hepatic metabolism in F1 generation, the mechanism of which requires further discussion.

AimRecurrent miscarriage (RM) is associated with numerous clinical factors. However, some RM occurred without specific factors. It has been revealed that some molecules such as hormones, miRNAs, and transcription factors are involved in RM by regulating proliferation, apoptosis, etc. However, the mechanism of RM has yet to be identified clearly. Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs that often act as sponges for miRNAs or binds to proteins involved in biological processes. However, the functional role of circRNAs in the uterine decidua of patients with early RM is still unclear. In this study, we aimed to investigate the mechanisms of circ-CYP24A1 in RM.MethodsThe Dual-Luciferase Activity Assay was designed to analyze the bonding between circ-CYP24A1 and miR-224, and miR-224 and prolactin receptor (PRLR) mRNA 3′UTR. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to observe the expression of circ-CYP24A1 and PRLR in the decidua. Rescue experiments were performed to investigate the regulating effects of circ-CYP24A1, miR-224, and PRLR. Western blotting was conducted to test the expression level of PRLR. The proliferation and apoptosis-related markers in Ishikawa cells were analyzed using CCK8, immunofluorescence staining, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay.ResultsIn this study, based on the microarray analysis data, we identified a high level of circ-CYP24A1 and PRLR in the decidua of patients with early RM. Based on the bioinformatics prediction, the binding relationship between circ-CYP24A1 and miR-224, as well as miR-224 and PRLR, were verified. Functional experiments demonstrated that circ-CYP24A1 regulated proliferation and apoptosis by binding to and inhibiting miR-224, resulting in increased PRLR expression. Taken together, this study provides new insights into the mechanism of RM.ConclusionIn this study, we found that circ-CYP24A1 plays a role in RM by impairing the balance of cell proliferation and apoptosis by sponging miR-224, thereby regulating PRLR.