title: Mild intrauterine hypoperfusion reproduces neurodevelopmental disorders observed in prematurity.
abstract: Severe intrauterine ischemia is detrimental to the developing brain. The impact of mild intrauterine hypoperfusion on neurological development, however, is still unclear. We induced mild intrauterine hypoperfusion in rats on embryonic day 17 via arterial stenosis with metal microcoils wrapped around the uterine and ovarian arteries. All pups were born with significantly decreased birth weights. Decreased gray and white matter areas were observed without obvious tissue damage. Pups presented delayed newborn reflexes, muscle weakness, and altered spontaneous activity. The levels of proteins indicative of inflammation and stress in the vasculature, i.e., RANTES, vWF, VEGF, and adiponectin, were upregulated in the placenta. The levels of mRNA for proteins associated with axon and astrocyte development were downregulated in fetal brains. The present study demonstrates that even mild intrauterine hypoperfusion can alter neurological development, which mimics the clinical signs and symptoms of children with neurodevelopmental disorders born prematurely or with intrauterine growth restriction.
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Ohshima
authors.affiliation: Institut de Neurosciences de la Timone, UMR7289, CNRS, Aix Marseille Université, Marseille 13005, France.
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Coq
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Otani
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
authors.forename: Yorito
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya 466-8550, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Harada-Shiba
authors.affiliation: Department of Stroke and Cerebrovascular Diseases, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005317:Fetal Growth Retardation / Q000473:pathology; D007235:Infant, Premature, Diseases / Q000473:pathology*; D007249:Inflammation / Q000473:pathology; D065886:Neurodevelopmental Disorders / Q000473:pathology*; D036801:Parturition / Q000502:physiology; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000502:physiology; D014599:Uterus / Q000473:pathology; D066127:White Matter / Q000473:pathology