title: Polyhydramnios in Lrp4 knockout mice with bilateral kidney agenesis: Defects in the pathways of amniotic fluid clearance.
abstract: 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.
authors: Department of Neuroplasticity, Institute of Pathogenesis and Disease Prevention, Graduate School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Japan.|Department of Biological Sciences for Intractable Neurological Diseases, Institute for Biomedical Sciences, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors: Hiroshi
authors: H
authors: Tanahashi
authors: Department of Neuroplasticity, Institute of Pathogenesis and Disease Prevention, Graduate School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors: Qing-Bao
authors: QB
authors: Tian
authors: Department of Anatomy, Kitasato University School of Medicine, 1-15-1, Kitasato, Sagamihara, Kanagawa 252-0374, Japan.
authors: Yoshinobu
authors: Y
authors: Hara
authors: Department of Anatomy, Kitasato University School of Medicine, 1-15-1, Kitasato, Sagamihara, Kanagawa 252-0374, Japan.
authors: Hiroyuki
authors: H
authors: Sakagami
authors: Research Team for Aging Neuroscience, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Sakae-cho, Itabashi, Tokyo 173-0015, Japan.
authors: Shogo
authors: S
authors: Endo
authors: Department of Neuroplasticity, Institute of Pathogenesis and Disease Prevention, Graduate School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Japan.|Department of Biological Sciences for Intractable Neurological Diseases, Institute for Biomedical Sciences, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors: Tatsuo
authors: T
authors: Suzuki
mesh_terms: D000650:Amnion / Q000378:metabolism; D000653:Amniotic Fluid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism; D004573:Electrolytes / Q000737:chemistry; D005260:Female; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D026502:LDL-Receptor Related Proteins; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009215:Myometrium / Q000378:metabolism / Q000473:pathology; D009994:Osmolar Concentration; D010920:Placenta / Q000378:metabolism; D006831:Polyhydramnios / Q000209:etiology* / Q000378:metabolism; D011247:Pregnancy; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics*
chemical_list: C496021:Aqp1 protein, mouse; C491638:Aqp9 protein, mouse; D020346:Aquaporins; D004573:Electrolytes; D026502:LDL-Receptor Related Proteins; C116415:Lrp4 protein, mouse; D037662:Pulmonary Surfactant-Associated Protein A; D011973:Receptors, LDL; D051398:Aquaporin 1