NLRP3 inflammasome-mediated Pyroptosis induce Notch signal activation in endometriosis angiogenesis.

Endometriosis is characterized by the presence of endometrial tissue outside the uterus that not only causes severe pelvic pain and infertility but also increased risk for ovarian carcinogenesis in women of reproductive age. Here, we found that angiogenesis was increased and accompanied with up-regulation of Notch1 in human endometriotic tissue sample, which is associated with pyroptosis induced by activation of endothelial NLRP3 inflammasome. Further, in endometriosis model induced in wild type and NLRP3-deficient (NLRP3-KO) mice, we found that deficiency of NLRP3 suppressing the development of endometriosis. In vitro, inhibiting the activation of NLRP3 inflammasome prevents LPS/ATP-induced tube formation in endothelial cells. Meanwhile, knockdown NLRP3 expression by gRNA disrupt the interaction between Notch1 and HIF-1α under the inflammatory microenvironment. This study demonstrates that activation of NLRP3 inflammasome-mediated pyroptosis affects angiogenesis in endometriosis via Notch1-dependent manner.

Associations between IGFBP1 gene polymorphisms and the risk of preeclampsia and fetal growth restriction.

IGFBP1 plays a critical role in the pathogenesis of preeclampsia (PE), but the association between single nucleotide polymorphism (SNP) of IGFBP1 gene and PE susceptibility has not yet been determined. In our study, 229 women with PE and 361 healthy pregnant (non-PE) women were enrolled to investigate its association via TaqMan genotyping assay. In addition, the protein levels of IGFBP1 under different genotypes were explored by ELISA and IHC. We found that IGFBP1 SNP rs1065780A > G was associated with an decreased risk for PE. Women with GG (P = 0.027) or AG (Padj. = 0.023) genotype manifested a significantly lower risk for PE compared to women with AA genotype. In PE group, women carrying G allele exhibited greater fetal birth weight, lower diastolic BP, and lower levels of ALT and AST. The G genotype was found significantly less frequently in the severe preeclampsia (SPE) group than in the non-PE group (GG vs. AA, P = 0.007; G vs. A, P = 0.006). Additionally, women in the PE group who experienced fetal growth restriction (FGR) reflected a lower level of the allele G than did the non-FGR group (P = 0.032); this was not the case for the non-PE group.Rs1065780A>G elevated IGFBP1 protein level in plasma and decidua in PE group. In conclusion Chinese Han women with the SNP IGFBP1 rs1065780 occupied by G exhibited a lower risk of developing PE relative to women with the A genotype and augured for improved pregnancy outcomes through elevation of IGFBP1 protein level.

Genetic Variations in Angiotensinogen Gene and Risk of Preeclampsia: A Pilot Study.

Preeclampsia (PE) is a typical hypertensive disorders of pregnancy (HDP) which can cause substantial morbidity and mortality in both pregnant women and fetuses. The renin-angiotensin system (RAS) genes are the main HDP-causing genes, and Angiotensinogen (AGT) as the initial substrate can directly reflect the activity of the entire RAS. However, the association between AGT SNPs and PE risk has rarely been confirmed. This study was carried out to determine whether AGT SNPs could affect the risk of PE in 228 cases and 358 controls. The genotyping result revealed that the AGT rs7079 TT carrier was related to increased PE risk. Further stratified analysis illustrated that the rs7079 TT genotype significantly increased the PE risk in subgroups of Age < 35, BMI < 25, Albumin (ALB) ≥ 30 and Aspartate aminotransferase (AST) < 30. These findings demonstrated that the rs7079 might be a promising candidate SNP strongly associated with PE susceptibility.