Placental Igf1 overexpression sex-specifically impacts mouse placenta structure, altering offspring striatal development and behavior

Abstract

Insulin-like growth factor 1 (IGF1) is primarily produced in the placenta and is essential for neurodevelopment. Specifically, how placental IGF1 production persistently influences the brain is unclear, but with rates of complicated pregnancies on the rise, understanding placental contributions to child outcomes is paramount. We hypothesize that placental Igf1 expression alters fetal neurodevelopment relevant to neurodevelopmental disorders. Therefore, this study evaluated the effects of placental Igf1 overexpression on embryonic and postnatal brain development, particularly for striatum, a region highly linked to neurodevelopmental disorders. Placental overexpression altered placenta structure and function distinctly in females and males. Early differences in placental function altered the trajectory of striatal development, as adult females showed persistent changes in striatal cell composition and behavior while males were less affected. Overall, these results demonstrate that placental Igf1 expression alters striatal development and behavior relevant to neurodevelopmental disorders. These findings expand our understanding of placental influence on neurodevelopment and will aid in targeting placental biology in preventive interventions.

Keywords: CRISPR; Insulin-like growth factor 1; Neurodevelopment; Neurodevelopmental disorders; Placenta; Striatum.