In this issue of the JCI, Dupont, Berg, and co-authors provide strong evidence that impaired placental perfusion, placental ischemia, increased soluble fms-like tyrosine kinase 1 (sFLT1), and a maternal preeclampsia–like phenotype are associated with an inability to upregulate the l-tryptophan–derived l-kynurenine pathway during pregnancy in mice with blunted renal reserve. This evidence concerns the gene FLT1 and ischemia.