In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver.
J Dev Orig Health Dis
; 10(3): 353-361, 2019 06.
Article
en En
| MEDLINE
| ID: mdl-30968813
ABSTRACT
The soluble fms-like tyrosine kinase factor 1 (sFlt-1) is a major contributor to antiangiogenesis during preeclampsia. However, little is known about the effects of sFlt-1 on fetal health. In this study we aim to evaluate the effects of the sFlt-1 concentration during pregnancy on fetal liver physiology. We used adenoviral gene delivery in Sprague-Dawley dams (seven females, 10 weeks old) during mid-gestation (gestational day 8) with adenovirus overexpressing sFlt-1, and age-matched controls (six females, 10 weeks old) with empty adenoviral virus in order to quantify the sFlt-1 concentrations in pregnant dams. Dams exposed to adenoviral sFlt-1 delivery were subdivided into a low (n=4) and high sFlt-1 (n=3) group based on host response to the virus. One-way analysis of variance showed that fetuses (five per dam) exposed to high sFlt-1 concentrations in utero show fetal growth restriction (1.84±0.043 g high sFlt-1 v. 2.32±0.036 g control; mean (M)±s.e.m.; P<0.001), without hypertension or proteinuria in the dams. In continuation, the microarray analysis of the fetal liver of the high sFlt-1 group showed significant enrichment of key genes for fatty acid metabolism and Ppara targets. In addition, using pyrosequencing, we found that the Ppara enrichment in the high sFlt-1 group is accompanied by decreased methylation of its promoter (1.89±0.097 mean % methylation in high sFlt-1 v. 2.26±0.095 mean % methylation in control, M±s.e.m., P<0.02). Our data show that high sFlt-1 concentrations during pregnancy have detrimental effects on the fatty acid metabolism genes and the Ppara targets in the fetal liver.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Efectos Tardíos de la Exposición Prenatal
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Regulación de la Expresión Génica
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Receptor 1 de Factores de Crecimiento Endotelial Vascular
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Retardo del Crecimiento Fetal
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Feto
/
Hígado
Tipo de estudio:
Etiology_studies
Límite:
Animals
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Pregnancy
Idioma:
En
Revista:
J Dev Orig Health Dis
Año:
2019
Tipo del documento:
Article
País de afiliación:
Países Bajos