LAUSR

Modeling a pregnancy disorder Preeclampsia, a dangerous pregnancy disorder marked by high blood pressure, can lead to premature birth and be life-threatening to the mother and baby. Research leading to effective treatments has been hampered by a lack of informative animal models. Ho et al. identified ELABELA as a hormone produced by the placenta whose levels are lower in preeclampsia (see the Perspective by Wirka and Quertermous). ELABELA-deficient pregnant mice showed clinical signs of preeclampsia, including high blood pressure and elevated urine protein. A proportion of embryos lacking ELABELA displayed defective heart development, and full-term pups had low birth weights. Science, this issue p. 707; see also p. 643 ELABELA is a placental hormone that functions in preeclampsia and heart development during embryogenesis. Preeclampsia (PE) is a gestational hypertensive syndrome affecting between 5 and 8% of all pregnancies. Although PE is the leading cause of fetal and maternal morbidity and mortality, its molecular etiology is still unclear. Here, we show that ELABELA (ELA), an endogenous ligand of the apelin receptor (APLNR, or APJ), is a circulating hormone secreted by the placenta. Elabela but not Apelin knockout pregnant mice exhibit PE-like symptoms, including proteinuria and elevated blood pressure due to defective placental angiogenesis. In mice, infusion of exogenous ELA normalizes hypertension, proteinuria, and birth weight. ELA, which is abundant in human placentas, increases the invasiveness of trophoblast-like cells, suggesting that it enhances placental development to prevent PE. The ELA-APLNR signaling axis may offer a new paradigm for the treatment of common pregnancy-related complications, including PE.