Maternal and Sex-Specific Fetal Characteristics of Three Different Mouse Models for Fetal Programming by Preeclampsia

Epidemiological data shows that preeclampsia increases the susceptibility for cardiovascular and metabolic diseases later in life in mother and offspring. This is usually referred to as “fetal programming” or “epigenetic programming”. However, conclusive data on causative factors and molecular mechanisms is lacking. This could potentially be examined in animal models, but preeclampsia is a multifactorial disease for which the perfect animal model does not exist. Here we compare the maternal and fetal status at the end of preeclamptic pregnancy in several mouse models, in order to unravel the mechanisms possibly involved in long‐term programming of health. We employed three C57Bl/6 mouse models mimicking specific parts of the phenotype of preeclampsia: the sFlt+LPS model, a combination of an antiangiogenic and a proinflammatory factor; the L‐NAME model, where vasoconstriction is induced; and the LXR agonist model, which is shown to induce metabolic distortion and antiangiogenesis. Interventions took place at gestational day 8 or 10. Right before delivery, at gestational day 18, we compared maternal and fetal phenotypes between the models. Elevated maternal systolic blood pressure was found in sFlt+LPS and L‐NAME dams, while to our surprise blood pressure was decreased in the LXR agonist model. Albuminurea was only found in the sFlt+LPS model. Maternal circulating insulin, an important fetal growth factor, was found decreased in the LXR agonist model, while no changes were found in free thiols, a measure of oxidative status. Consequences for fetuses were model‐ and sex‐specific. LXR agonist and sFlt+LPS fetuses were growth restricted, with brain sparing taking place in male fetuses only. Placental efficacy, as measured by body weight/placenta ratio, was lower for male LXR agonist and L‐NAME fetuses. Disturbed fetal growth is known to have long‐lasting metabolic consequences for the fetus. To conclude, we show here that different animal models for preeclampsia result in different maternal and fetal characteristics, with the sFlt+LPS model showing the most resemblance with clinical preeclampsia. A long‐term study in the sFlt+LPS model will give insight in programming effects and programming mechanisms of preeclampsia for both mother and offspring. Support or Funding Information This work was supported by the Netherlands Organization for Health Research and Development (ZonMW, grant number 91211053 to T.P.). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .