Evaluation of the Effect of the Fibroblast Growth Factor Type 2 (FGF-2) Administration on Placental Gene Expression in a Murine Model of Preeclampsia Induced by L-NAME

Abstract

The abnormal implantation of the trophoblast during the first trimester of pregnancy precedes the appearance of the clinical manifestations of preeclampsia (PE), which is a hypertensive disorder of pregnancy. In a previous study, which was carried out in a murine model of PE that was induced by NG-nitro-L-arginine methyl ester (L-NAME), we observed that the intravenous administration of fibroblast growth factor 2 (FGF2) had a hypotensive effect, improved the placental weight gain and attenuated the fetal growth restriction, and the morphological findings that were induced by L-NAME in the evaluated tissues were less severe. In this study, we aimed to determine the effect of FGF2 administration on the placental gene expression of the vascular endothelial growth factor (VEGFA), VEGF receptor 2 (VEGFR2), placental growth factor, endoglin (ENG), superoxide dismutase 1 (SOD1), catalase (CAT), thioredoxin (TXN), tumor protein P53 (P53), BCL2 apoptosis regulator, Fas cell surface death receptor (FAS), and caspase 3, in a Sprague Dawley rat PE model, which was induced by L-NAME. The gene expression was determined by a real-time polymerase chain reaction using SYBR green. Taking the vehicle or the L-NAME group as a reference, there was an under expression of placental VEGFA, VEGFR2, ENG, P53, FAS, SOD1, CAT, and TXN genes in the group of L-NAME + FGF2 (p < 0.05). The administration of FGF2 in the murine PE-like model that was induced by L-NAME reduced the effects that were generated by proteinuria and the increased BP, as well as the response of the expression of genes that participate in angiogenesis, apoptosis, and OS. These results have generated valuable information regarding the identification of molecular targets for PE and provide new insights for understanding PE pathogenesis.

Exploring maternal-fetal interface with in vitro placental and trophoblastic models

“…First, the researchers studied the Wnt and MAPK signaling pathways during the 6–8 weeks of gestation. They identified the basal medium components, including epidermal growth factor (EGF) ( Cheng et al, 2022 ) and fibroblast growth factor 2 (FGF-2) ( Martinez-Fierro et al, 2022 ), and enzymatically digested the placenta during early pregnancy. EpCAM-labeled trophoblast cells, which are a specific subtype of trophoblast cells, were obtained.…”

Sex-Specific DNA Methylation and Gene Expression Changes in Mouse Placentas After Early Preimplantation Alcohol Exposure

“…Male ethanolexposed placentas displayed altered methylation and/or expression patterns in several genes that are directly linked to embryonic growth restriction. For example, a study recently showed that injecting fibroblast growth factor 2 (Fgf2; downregulated in male ethanol-exposed placentas) into a rat model of preeclampsia improved clinical outcomes, including attenuating fetal growth restriction (Martinez-Fierro et al, 2022). Mutation of Fgf1 (increased methylation in male ethanol-exposed placentas) has been linked to preeclampsia in humans (Marwa et al, 2016), while Bmp6 (decreased methylation in male ethanolexposed placentas) was downregulated in the fetal kidneys of rats with intrauterine growth restriction in a model of induced hypertension due to chronic insulin administration (Bursztyn et al, 2006).…”

Pathogenesis of Pregnancy-Related Complications

“…Martinez-Fierro et al [ 7 ] present interesting findings on the pathogenesis of preeclampsia, evaluating the effect of the administration of fibroblast growth factor type 2 on the placental expression of various genes involved in angiogenesis and apoptosis in an experimental murine model of preeclampsia. The administration of fibroblast growth factor type 2 reduced the effects generated by proteinuria and hypertension and also impacted the expression of studied genes.…”