Int6/eIF3e Silencing Promotes Placenta Angiogenesis in a Rat Model of Pre-eclampsia

Abstract

We investigated whether stable eukaryotic translation initiation factor 3e/inter 6 (eIF-3e/Int6) RNA-silencing (siRNA-Int6) can ameliorate pre-eclampsia (PE) by promoting angiogenesis in an N-nitro-L-arginine methyl ester (L-NAME)-induced rat pre-eclampsia (PE) model. Twenty-four pregnant female Sprague–Dawley rats were allocated into 4 groups, including controls (Con) without any treatment, and 18 from gestational day (GD) 7 to GD17 L-NAME-treated rats, which were divided into stable siRNA-Int6 transfected (siRNA-Int6), negative vector control siRNA (NC-siRNA) and PE control (PE-Con) groups. All adenovirus siRNA transfections were performed on GD7 via intravenous tail injection. On GD0, GD11 and GD17, blood pressure, and on GD6 and GD17, protein estimations in 24 h urine samples were conducted. All animals were sacrificed on GD18. In the PE-Con group, placental Int6 was expressed to a significantly greater level than in the Con group, which was reversed by the application of siRNA-Int6. Blood pressure and proteinuria were significantly lower in the siRNA-Int6 group than in the PRE-Con group. As shown by CD31 and IB4 expression, placental micro-vascular density (MVD) was significantly higher in the siRNA-Int6 group than in the PE-Con and NC-siRNA groups, which has accompanied by enhanced trophoblast invasion. Int6 silencing alleviated the maternal clinical manifestations of pre-eclampsia and promoted placental angiogenesis in pregnant L-NAME-treated rats.

Cinnamaldehyde mitigates placental vascular dysfunction of gestational diabetes and protects from the associated fetal hypoxia by modulating placental angiogenesis, metabolic activity and oxidative stress

“…Using a stainless-steel razor blade, placentae were cut horizontally at their half thickness [39,40] to expose the full face of the placenta for better examining the histopathological changes across a wide surface area of the different placental layers. Samples were dehydrated, cleared, and paraffin embedded.…”

The Impact of Oxidative Stress of Environmental Origin on the Onset of Placental Diseases

“…Altered methylation in the placentas was observed for 46 DMRs following exposition to triclosan (37 DMRs), confirming alterations nearby imprinted genes, nevertheless without specific alterations nearby genes directly involved in OS metabolism [ 144 ]. Consistently, Basak and coworkers showed in the trophoblast model HTR8/SV-neo that BPA exposure (1 nM) decreased promoter methylation of genes involved in metabolic and OS, such as GSR, PRDX2, GPX7, and GPX3, among others [ 145 ].…”

Comparative proteomic analysis identifies differentially expressed proteins and reveals potential mechanisms of traumatic heterotopic ossification progression

“…Hif1α expression coincides with the expression of chondrogenesis factor such as Sox9 [(sex determining region Y)-box 9] and pharmacologic inhibition of Hif1α can significantly decreased extraskeletal bone formation [ 57 ]. Importantly, EIF3E can promote the vascular remodeling and development via Int6/eIF3e-HIFs pathway [ 58 ]. Based on this studies, it could probably be suggested that the higher expression of EIF3E, as revealed in this study, may promote the expression of HIF signaling and increase the progression of heterotopic ossification [ 59 ].…”