Figure 3.

Phenotype of the hsFLT1/rtTA mouse model. Analysis of fetal outcome (fetal weight, litter size, resorptions, and retardations) and the placental phenotype (placental weight, placental efficiency) at day 18.5 post coitum. (A–E) Consequences of ubiquitous maternal and/or fetal overexpression of human soluble fms-like tyrosine kinase 1 (hsFLT1) in fetal growth restriction (FGR) homozygous (hom), FGR heterozygous (het), or FGR wild-type (wt) fetuses, showing strong (A), medium (B), or mild (C) effects on fetal size in contrast to the control group, which did express hsFLT1 (D). Treating the dam with doxycycline (Dox) (single hsFLT1 mice) produced no negative effects on fetal size (E). These observations were confirmed by analysis of fetal weights (F) and by the correlation of fetal weight to placental hsFLT1 expression (G). Placental weight was decreased only in the FGR hom group upon the highest expression of hsFLT1 in fetus and dam (H), whereas placental efficiency (fetal weight/placental weight) is reduced in each FGR group in association with the corresponding hsFLT1 expression levels (I). Litter size (J) and number of resorptions (K) did not vary between mouse cohorts; however, signs of retardation, such as cyanosis or demise of the fetus, increased in frequency upon hsFLT1 expression (L). Data show hsFLT1/rtTA (FGR) or single hsFLT1 (Dox control) mice treated with Dox at early to midgestation and untreated controls. *p < 0.05, **p < 0.01, ***p < 0.001 as determined by the Kruskal–Wallis test with Dunn's post hoc test. Correlation analysis was performed with Spearman's rank correlation coefficient.