Placental programming of anxiety in adulthood revealed by Igf2-null models.
Imprinted, maternally silenced insulin-like growth factor-2 is expressed in both the foetus and placenta and has been shown to have roles in foetal and placental development in animal models. Here we compared mice engineered to be null for the placenta-specific P0 transcript (insulin-like growth factor-2-P0 KO) to mice with disruptions of all four insulin-like growth factor-2 transcripts, and therefore null for insulin-like growth factor-2 in both placenta and foetus (insulin-like growth factor-2-total KO). Both models lead to intrauterine growth restriction but dissociate between a situation where there is an imbalance between foetal demand and placental supply of nutrients (the insulin-like growth factor-2-P0 KO) and one where demand and supply is more balanced (the insulin-like growth factor-2-total KO). Increased reactivity to anxiety-provoking stimuli is manifested later in life only in those animals where there is a mismatch between placental supply and foetal demand for nutrients during gestation. Our findings further distinguish placental dysfunction from intrauterine growth restriction and reveal a role for the placenta in long-term programming of emotional behaviour.
Behavioral Genetics Group, School of Psychology, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff CF10 3AT, UK.
Mikael Allan
MA
Mikaelsson
Miguel
M
Constância
Claire L
CL
Dent
Lawrence S
LS
Wilkinson
Trevor
T
Humby
D000161:Acoustic Stimulation; D000375:Aging / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000235:genetics / Q000473:pathology*; D001522:Behavior, Animal; D001724:Birth Weight; D001835:Body Weight; D004195:Disease Models, Animal; D005106:Exploratory Behavior; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007335:Insulin-Like Growth Factor II / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D018782:Maze Learning; D051379:Mice; D018345:Mice, Knockout; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
D007335:Insulin-Like Growth Factor II