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Mild intrauterine hypoperfusion in rats reproduces neurodevelopmental disorders observed in children with fetal growth restriction
Children with fetal grow restriction (FGR) and its resultant low birthweight (LBW) have a higher risk for developing neurodevelopmental disorders, which include attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder. More than half of the cases of FGR are reportedly caused by placental insufficiency, which is a process that leads to a decrease in placental blood flow and/or transplacental transfer of oxygen and nutrients to the fetus. Hence, intrauterine hypoperfusion models are probably the most important model to study the pathophysiology and consequences of FGR-LBW. We developed a rat model of mild intrauterine hypoperfusion induced by arterial stenosis with metal microcoils wrapped around the uterine and ovarian arteries on embryonic day 17. Most pups were born with significantly decreased birth weights. These LBW rat presented 1) decreased gray and white matter areas without obvious tissue damage, and 2) altered behaviors, namely delayed newborn reflexes, hyperactivity, and lack of sociability. We have been investigating the pathophysiology of the FGR-LBW rats and found that they exhibit, for instance, 1) mild inflammation in placenta, 2) diminished post-active depression, and 3) altered levels and distributions of metabolites in the brain. This model mimics the clinical signs and symptoms of children with neurodevelopmental disorders born FGR-LBW and could be a useful model to study the mechanisms of FGR-LBW harmful effects and to develop therapeutic interventions for the disorders.
Date:
5 September 2022, 16:00
Venue:
Sherrington Building, off Parks Road OX1 3PT
Venue Details:
Blakemore Lecture Theatre
Speaker:
Professor Masahiro Tsuji, MD, PhD (Department of Food and Nutrition, Kyoto Women’s University, Japan)
Organising department:
Department of Physiology, Anatomy and Genetics (DPAG)
Organiser:
Professor Zoltan Molnar (DPAG, University of Oxford)
Organiser contact email address:
zoltan.molnar@dpag.ox.ac.uk
Host:
Professor Zoltan Molnar (DPAG, University of Oxford)
Part of:
Neuroscience Theme Guest Speakers (DPAG)
Booking required?:
Not required
Audience:
Members of the University only
Editor:
Talitha Smith
