Background/Aims: Paternal exposure to adverse environmental conditions can act on offspring’s phenotype and influence offspring’s later life disease risk. Our study was designed to examine the effect of feeding male rats before mating a high-fat, high-sucrose and high-salt diet (HFSSD) over two generations (F0 and F1) on their offspring’s (F2) liver function and gut microbiome composition. Methods: Male F0 rats and male F1 rats were fed either control diet or HFSSD before mating. Liver function of F2 offspring was investigated, and their gut microbiome composition was analyzed by 16S rRNA gene sequencing in the F2 offspring of rats whose fathers and grandfathers were fed with control diet (CD) (F0CD+F1CD-F2 group) or HFSSD prior to mating (F0HD+F1HD-F2 group). Results: F2 offspring had higher serum aspartate aminotransferase activity (female, p < 0.05 and male, p < 0.01 respectively) compared with control. Shannon indexes of gut microbiota indicated a significantly higher diversity in the female F0HD+F1HD-F2 as compared to F0CD+F1CD-F2 female offspring (p < 0.01). The dominant phyla of all the groups were Bacteroidetes, Firmicutes and Proteobacteria. There were significant differences in gut bacterial community composition at phyla and genus level between the F0CD+F1CD-F2 and F0HD+F1HD-F2. Furthermore, the variation in the relative abundance (percentage) of bacterial genus in the F2 offspring was associated with liver function alterations induced by a paternal pre-conceptional unhealthy diet. Male F0HD+F1HD-F2 offspring had higher serum cholesterol, high density lipoproteins as well as low density lipoproteins concentrations compared to the corresponding male control rats. Conclusion: Taken together, our findings suggested that a paternal pre-conceptional unhealthy diet predisposes the offspring to mild liver function alterations and alterations of gut microbiota in later life. Effects on lipids were sex-specific and only seen in male offspring.

Background This study aims to explore whether plasma endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in the first trimester can be used as a predictor of hypertensive disorders of pregnancy (HDP), and compare it with placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) to evaluate its prediction of HDP value. Methods This is a prospective cohort study that records the medical history of the pregnant women included in the study at 11–13 weeks’ gestation, and analyzes serum biochemical markers including EG-VEGF, PIGF, sFlt-1 and sFlt-1/PIGF. The predictive values of these tests were determined. We used the receiver operating characteristic (ROC) curve to find the optimal cut-off value for each biomarker and compare the operating characteristics (sensitivity, specificity). Logistic regression analysis was used to create a prediction model for HDP based on maternal characteristics and maternal biochemistry. Results Data were obtained from 205 pregnant women. 17 cases were diagnosed with HDP, the incidence rate was 8.2% (17/205). Women who developed HDP had a significantly higher body mass index (BMI) and mean arterial pressure (MAP). Serum EG-VEGF levels in the first trimester are significantly higher in pregnant women with HDP. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value(NPV) of serum EG-VEGF levels more than 227.83 pg/ml for predicting HDP were 43%, 93%, 86% and 62%, respectively. We established a prediction model in the first trimester include maternal BMI, MAP, and EG-VEGF, with an AUC of 0.8861 (95%CI: 0.7905–0.9818), which is better than using EG-VEGF alone (AUC: 0.66). Conclusion This study demonstrated that serum EG-VEGF is a promising biomarker for predicting HDP in the first trimester. It has better predictive performance compared with the currently used biomarkers like PIGF and sFlt-1. Combining maternal clinical characteristics and biochemical tests at 11–13 weeks can effectively identify women at high risk of HDP.