Publication

In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver

Stojanovska, V., Holwerda, K. M., van der Graaf, A. M., Verkaik-Schakel, R. N., Boekschoten, M. V., Faas, M. M., Scherjon, S. A. & Plösch, T., Jun-2019, In : Journal of developmental origins of health and disease. 10, 3, p. 353-361 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Stojanovska, V., Holwerda, K. M., van der Graaf, A. M., Verkaik-Schakel, R. N., Boekschoten, M. V., Faas, M. M., ... Plösch, T. (2019). In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver. Journal of developmental origins of health and disease, 10(3), 353-361. https://doi.org/10.1017/S2040174418000831

Author

Stojanovska, V ; Holwerda, K M ; van der Graaf, A M ; Verkaik-Schakel, R N ; Boekschoten, M V ; Faas, M M ; Scherjon, S A ; Plösch, T. / In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver. In: Journal of developmental origins of health and disease. 2019 ; Vol. 10, No. 3. pp. 353-361.

Harvard

Stojanovska, V, Holwerda, KM, van der Graaf, AM, Verkaik-Schakel, RN, Boekschoten, MV, Faas, MM, Scherjon, SA & Plösch, T 2019, 'In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver', Journal of developmental origins of health and disease, vol. 10, no. 3, pp. 353-361. https://doi.org/10.1017/S2040174418000831

Standard

In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver. / Stojanovska, V; Holwerda, K M; van der Graaf, A M; Verkaik-Schakel, R N; Boekschoten, M V; Faas, M M; Scherjon, S A; Plösch, T.

In: Journal of developmental origins of health and disease, Vol. 10, No. 3, 06.2019, p. 353-361.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Stojanovska V, Holwerda KM, van der Graaf AM, Verkaik-Schakel RN, Boekschoten MV, Faas MM et al. In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver. Journal of developmental origins of health and disease. 2019 Jun;10(3):353-361. https://doi.org/10.1017/S2040174418000831


BibTeX

@article{f1034e043ff94a7cb07ff6d667c60ab6,
title = "In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver",
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.",
keywords = "animal, developmental stage, epigenetics, fetus, general, molecular/cellular, small animals, GROWTH-FACTOR RECEPTOR-1, BIRTH-WEIGHT, ANGIOGENIC FACTORS, PPAR-ALPHA, RESTRICTION, RETARDATION, METABOLISM, OBESITY, ALTERS, FLT-1",
author = "V Stojanovska and Holwerda, {K M} and {van der Graaf}, {A M} and Verkaik-Schakel, {R N} and Boekschoten, {M V} and Faas, {M M} and Scherjon, {S A} and T Pl{\"o}sch",
year = "2019",
month = "6",
doi = "10.1017/S2040174418000831",
language = "English",
volume = "10",
pages = "353--361",
journal = "Journal of developmental origins of health and disease",
issn = "2040-1744",
publisher = "Cambridge University Press",
number = "3",

}

RIS

TY - JOUR

T1 - In utero sFlt-1 exposure differentially affects gene expression patterns in fetal liver

AU - Stojanovska, V

AU - Holwerda, K M

AU - van der Graaf, A M

AU - Verkaik-Schakel, R N

AU - Boekschoten, M V

AU - Faas, M M

AU - Scherjon, S A

AU - Plösch, T

PY - 2019/6

Y1 - 2019/6

N2 - 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.

AB - 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.

KW - animal

KW - developmental stage

KW - epigenetics

KW - fetus

KW - general

KW - molecular/cellular

KW - small animals

KW - GROWTH-FACTOR RECEPTOR-1

KW - BIRTH-WEIGHT

KW - ANGIOGENIC FACTORS

KW - PPAR-ALPHA

KW - RESTRICTION

KW - RETARDATION

KW - METABOLISM

KW - OBESITY

KW - ALTERS

KW - FLT-1

U2 - 10.1017/S2040174418000831

DO - 10.1017/S2040174418000831

M3 - Article

VL - 10

SP - 353

EP - 361

JO - Journal of developmental origins of health and disease

JF - Journal of developmental origins of health and disease

SN - 2040-1744

IS - 3

ER -

ID: 80052758