The effect of prepregnancy obesity and sFlt-1-induced preeclampsia-like syndrome on fetal programming of adult vascular function in a mouse model.
OBJECTIVE
The purpose of this study was to test the hypothesis that prepregnancy obesity and soluble fms-like tyrosine kinase-1 (sFlt-1)-induced preeclampsia lead to altered vascular function in the offspring later in life.


METHODS
CD-1 female mice were placed on a low-fat (LF) or high-fat (HF) diet before mating. On day 8 of pregnancy, the HF mice were injected with adenovirus that carried either sFlt-1 (HF sFlt-1) or murine immunoglobulin G2alpha Fc fragment (HF mFc). LF dams received saline solution. After being weaned, all offspring were placed on a standard diet. At 3 months of age, the carotid artery was isolated for in vitro vascular reactivity studies.


RESULTS
Among male offspring, the response to phenylephrine was significantly lower in the HF sFlt-1 group. The response to serotonin in males and to thromboxane in females was lower in the HF sFlt-1 and HF mFc groups. In females, the HF sFlt-1 and LF groups displayed less relaxation to acetylcholine. The response to phenylephrine was significantly lower in females than males in the HF mFc and LF groups. The response to thromboxane was significantly lower in the HF sFlt-1 females, compared with males.


CONCLUSIONS
Prepregnancy obesity and preeclampsia alter fetal programming of adult vascular function. The mechanism is complex and gender specific.
Byers
Benjamin D
BD
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX, USA.
Betancourt
Ancizar
A
Lu
Fangxian
F
Hankins
Gary D V
GD
Longo
Monica
M
Saade
George R
GR
Bytautiene
Egle
E