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.

中文翻译：

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ELABELA缺乏促进小鼠先兆子痫和心血管畸形

模拟妊娠疾病 先兆子痫是一种以高血压为特征的危险妊娠疾病，可导致早产并对母婴造成生命危险。由于缺乏信息丰富的动物模型，导致有效治疗的研究受到阻碍。何等人。将 ELABELA 鉴定为胎盘产生的激素，其水平在先兆子痫中较低（参见 Wirka 和 Quertermous 的观点）。缺乏 ELABELA 的怀孕小鼠表现出先兆子痫的临床症状，包括高血压和尿蛋白升高。一部分缺乏 ELABELA 的胚胎表现出心脏发育缺陷，足月幼崽出生体重低。科学，这个问题 p。707; 另见第。643 ELABELA 是一种胎盘激素，在胚胎发生过程中在先兆子痫和心脏发育中起作用。先兆子痫 (PE) 是一种妊娠高血压综合征，影响所有妊娠的 5% 至 8%。虽然 PE 是胎儿和母体发病率和死亡率的主要原因，但其分子病因尚不清楚。在这里，我们展示了 ELABELA (ELA)，一种 apelin 受体 (APLNR，或 APJ) 的内源性配体，是一种由胎盘分泌的循环激素。Elabela 但不是 Apelin 基因敲除的怀孕小鼠表现出类似 PE 的症状，包括蛋白尿和由于胎盘血管生成缺陷导致的血压升高。在小鼠中，外源性 ELA 的输注使高血压、蛋白尿和出生体重正常化。ELA 在人类胎盘中含量丰富，可增加滋养层样细胞的侵袭性，表明它可促进胎盘发育以预防 PE。