It is widely accepted that diabetes mellitus impairs placental development, but the mechanism by which the disease operates to impair development remains controversial. In this study, we demonstrated that pregestational diabetes mellitus (PGDM)-induced defects in placental development in mice are mainly characterized by the changes of morphological structure of placenta. The alteration of differentiation-related gene expressions in trophoblast cells rather than cell proliferation/apoptosis is responsible for the phenotypes found in mouse placenta. Meanwhile, excess reactive oxygen species (ROS) production and activated nuclear factor erythroid2-related factor 2 (Nrf2) signalling were observed in the placenta of mice suffering from PGDM. Using BeWo cells, we also demonstrated that excess ROS was produced and Nrf2 signalling molecules were activated in settings characterized by a high concentration of glucose. More interestingly, differentiation-related gene expressions in trophoblast cells were altered when endogenous Nrf2 expression is manipulated by transfecting Nrf2-wt or Nrf2-shRNA. In addition, PGDM interferes with autophagy in both mouse placenta and BeWo cells, implying that autophagy is also involved, directly or indirectly, in PGDM-induced placental phenotypes. Therefore, we revealed that dysfunctional oxidative stress-activated Nrf2 signalling and autophagy are probably responsible for PGDM-induced defects in the placental development of mice. The mechanism was through the interference with differentiation-related gene expression in trophoblast cells.
Subclinical hypothyroidism (SHT) is a common disorder that may represent early thyroid dysfunction and is related to adverse cardiovascular events. However, myocardial injuries induced by SHT are difficult to detect. Our previous study demonstrated that the cardiac magnetic resonance (CMR) myocardial longitudinal relaxation time (T1) mapping technique is a useful tool for assessing diffuse myocardial injuries in overt hypothyroidism patients. This study was designed to detect whether diffuse myocardial injuries were present in SHT by using the T1 mapping technique. We found that SHT participants had significantly increased native T1 values within four segments of the left ventricle (all p < 0.01), especially patients with thyroid-stimulating hormone (TSH) levels ≥10 µIU/mL, compared with those in the controls. In addition, the native T1 values were negatively correlated with free thyroxine (FT4) (r = −0.476, p = 0.003) and were positively correlated with TSH (r = 0.489, p = 0.002). Furthermore, left ventricular diastolic function estimated by the peak filling rate (PFR) was significantly lower in patients with TSH levels ≥10 µIU/mL than that in the controls (p < 0.05). In conclusion, diffuse myocardial injuries were present in SHT, and T1 mapping may be a useful tool for evaluating mild myocardial injuries in SHT at an early stage. Our study is the first to confirm myocardial injuries in SHT patients using T1 mapping.
Purpose: Preeclampsia (PE) is a severe disease that endangers the safety of mothers and fetuses worldwide. In the absence of specific treatments, more studies on novel predictive and diagnostic biomarkers for PE are required.Experimental design: Data-independent acquisition proteomics, with five biological replicates, was used to investigate the protein expression profiles of placental tissues from patients with PE and normal pregnant women.Results: In total, 52 differentially expressed proteins (DEPs) were identified, 34 of them were upregulated and 18 downregulated. Bioinformatics analyses revealed that PE was associated with multiple GO terms and KEGG pathways. Arginase-1 (ARG1), ferritin light chain (FTL), and RNA cytidine acetyltransferase (NAT10) were identified as hub proteins, which were further validated in placental tissues and maternal plasma by western blot and ELISA.Conclusions and clinical relevance: FTL expression was significantly lower in the placental tissues and early and late pregnancy plasma of patients with PE compared to that in normal pregnant women. This study is the first to propose that FTL may be a potential predictive and diagnostic biomarker for PE; it provides a proteomics insight for understanding the pathological mechanism of this disease.
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