Polyhydramnios in Lrp4 knockout mice with bilateral kidney agenesis: Defects in the pathways of amniotic fluid clearance.
Polyhydramnios in Lrp4 knockout mice with bilateral kidney agenesis: Defects in the pathways of amniotic fluid clearance.
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DOI：
10.1038/srep20241
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发表时间：
2016-02-05
影响因子：
4.6
通讯作者：
Suzuki T
中科院分区：
文献类型：
--
作者：
Tanahashi H;Tian QB;Hara Y;Sakagami H;Endo S;Suzuki T
妊娠中期至晚期的羊水量主要取决于胎儿肾脏的尿液排泄，部分取决于胎儿呼吸样运动期间胎儿肺部的液体分泌。尿液是胎儿呼吸样运动所必需的，这对胎儿肺部发育至关重要。双侧肾发育不全和/或尿路梗阻导致羊水过少，导致婴儿在出生后短期内因肺发育不全而死亡。Lrp 4作为聚集蛋白受体发挥作用，对神经肌肉接头的形成至关重要。在此，我们报告了Lrp 4基因敲除（Lrp 4 −/−）小鼠的新表型。大多数Lrp 4 −/−胎儿显示单侧或双侧肾脏发育不全，Lrp 4敲除导致羊水过多。Lrp 4的缺失损害了胎儿的吞咽和呼吸样运动，并下调了胎膜中的水通道蛋白-9和胎盘中的水通道蛋白-1的表达，这可能影响羊水清除。这些结果表明，Lrp 4 −/−胎儿的羊水清除受到影响，导致羊水过多，尽管尿液产生受损。我们的研究结果表明，羊水清除在调节羊水量方面起着至关重要的作用。
Amniotic fluid volume during mid-to-late gestation depends mainly on the urine excretion from the foetal kidneys and partly on the fluid secretion from the foetal lungs during foetal breathing-like movements. Urine is necessary for foetal breathing-like movements, which is critical for foetal lung development. Bilateral renal agenesis and/or obstruction of the urinary tract lead to oligohydramnios, which causes infant death within a short period after birth due to pulmonary hypoplasia. Lrp4, which functions as an agrin receptor, is essential for the formation of neuromuscular junctions. Herein, we report novel phenotypes of Lrp4 knockout (Lrp4−/−) mice. Most Lrp4−/− foetuses showed unilateral or bilateral kidney agenesis, and Lrp4 knockout resulted in polyhydramnios. The loss of Lrp4 compromised foetal swallowing and breathing-like movements and downregulated the expression of aquaporin-9 in the foetal membrane and aquaporin-1 in the placenta, which possibly affected the amniotic fluid clearance. These results suggest that amniotic fluid removal was compromised in Lrp4−/− foetuses, resulting in polyhydramnios despite the impairment of urine production. Our findings indicate that amniotic fluid removal plays an essential role in regulating the amniotic fluid volume.