Luo Kehuan, Thaete Larry G, Neerhof Mark G
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, NorthShore University HealthSystem, Evanston, IL, USA.
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, NorthShore University HealthSystem, Evanston, IL, USA Department of Obstetrics and Gynecology, University of Chicago Pritzker School of Medicine, Chicago, IL, USA
Reprod Sci. 2016 Aug;23(8):1028-36. doi: 10.1177/1933719115625839. Epub 2016 Jan 19.
Fetal growth restriction (FGR) is commonly associated with perinatal morbidity and mortality. Nitric oxide (NO) deficiency increases endothelin-1 (ET-1) production, and this increased ET-1 may contribute to the pathophysiology of NO deficiency-induced FGR. Using an endothelial NO synthase knockout mouse model of FGR, we sought to determine (a) the relative importance of maternal versus conceptus (fetal and placental) NO deficiency and (b) the contribution of ET-1 to the pathogenesis of FGR in this model. Fetal growth restriction occurred both with NO-deficient conceptuses in the setting of maternal NO production and with maternal NO deficiency in the setting of NO-producing conceptuses. Placental ET-1 expression was increased in NO-deficient dams, ET receptor A (ETA) production increased in endothelial nitric oxide synthase(+/-) placentas, and antagonism of ETA prevented FGR. These results demonstrate that both maternal and conceptus NO deficiency can contribute to FGR and suggest a role for ETA antagonists as therapeutic agents in FGR.
胎儿生长受限（FGR）通常与围产期发病率和死亡率相关。一氧化氮（NO）缺乏会增加内皮素-1（ET-1）的产生，而这种增加的ET-1可能导致NO缺乏诱导的FGR的病理生理学。使用FGR的内皮型NO合酶基因敲除小鼠模型，我们试图确定（a）母体与胎儿（胎儿和胎盘）NO缺乏的相对重要性，以及（b）ET-1在该模型中对FGR发病机制的贡献。在母体产生NO的情况下，NO缺乏的胎儿会出现胎儿生长受限，而在产生NO的胎儿情况下，母体NO缺乏也会导致胎儿生长受限。在NO缺乏的母鼠中，胎盘ET-1表达增加，在内皮型一氧化氮合酶（+/-）胎盘的ET受体A（ETA）产生增加，并且ETA的拮抗作用可预防FGR。这些结果表明，母体和胎儿NO缺乏均可导致FGR，并提示ETA拮抗剂作为FGR治疗药物的作用。
