Placental programming of anxiety in adulthood revealed by Igf2-null models

• Published in: Nature communications Vol. 4; no. 1; p. 2311
• Main Authors: Mikaelsson, Mikael Allan, Constância, Miguel, Dent, Claire L., Wilkinson, Lawrence S., Humby, Trevor
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2013; Nature Publishing Group
• Subjects: 631/136; 631/378/1689/1300; Acoustic Stimulation; Aging - pathology; Animals; Animals, Newborn; Anxiety - genetics; Anxiety - pathology; Behavior, Animal; Birth Weight; Body Weight; Disease Models, Animal; Exploratory Behavior; Female; Gene Expression Regulation, Developmental; Genomic Imprinting - genetics; Hippocampus - metabolism; Hippocampus - pathology; Humanities and Social Sciences; Insulin-Like Growth Factor II - deficiency; Insulin-Like Growth Factor II - genetics; Insulin-Like Growth Factor II - metabolism; Maze Learning; Medicin och hälsovetenskap; Mice; Mice, Knockout; multidisciplinary; Placenta - metabolism; Pregnancy; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms3311

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. Insulin-like growth factor-2 is implicated in foetal and placental development in mammals. Mikaelsson et al . study transgenic mice with disrupted insulin-like growth factor-2 signalling and find that their offspring are more anxious when they reach adulthood.