The effect of prepregnancy obesity and sFlt-1–induced preeclampsia-like syndrome on fetal programming of adult vascular function in a mouse model

• Published in: American journal of obstetrics and gynecology 2009-04, Vol.200 (4), p.432.e1-432.e7
• Main Authors: Byers, Benjamin D., DO, Betancourt, Ancizar, MS, Lu, Fangxian, MD, Hankins, Gary D.V., MD, Longo, Monica, MD, PhD, Saade, George R., MD, Bytautiene, Egle, MD
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Biological and medical sciences; Blood Vessels - physiology; CD-1; Diseases of mother, fetus and pregnancy; Female; Fetal Development; fetal programming; Gynecology. Andrology. Obstetrics; Male; Medical sciences; Metabolic diseases; Mice; Obesity; Obesity - complications; Obstetrics and Gynecology; Pre-Eclampsia - etiology; preeclampsia; Pregnancy; Pregnancy. Fetus. Placenta; sFlt-1; Vascular Endothelial Growth Factor Receptor-1 - administration & dosage
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2009.01.044

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. Study Design 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 G2α 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. Conclusion Prepregnancy obesity and preeclampsia alter fetal programming of adult vascular function. The mechanism is complex and gender specific.