Altered adult brain morphology in a mouse model of late-onset fetal growth restriction

Late-onset fetal growth restriction (FGR) from placental insufficiency results in progressive fetal hypoxia and is often associated with poor neurodevelopmental outcomes. In response to hypoxia, fetal brain sparing physiology is activated to protect the developing brain from injury via enhancing oxygen delivery. However, this protection may not be robust, and some brain regions remain susceptible to hypoxic injury. In addition, not all injury is manifested during fetal life, and may present in infant development. Using a mouse model of late-onset FGR where gestation is extended for 24 hours, equivalent to approximately 2 weeks in humans, we deployed longitudinal in vivo magnetic resonance imaging to assess structural brain development from birth to adulthood. Postterm fetuses showed significantly smaller volumes of the perirhinal and ectorhinal cortex regions compared to controls, with no differences observed between sexes. These brain regions, essential for recognition memory, exhibited progressively greater volume reductions with increasing postnatal age. Our findings add to the growing body of literature demonstrating that an adverse fetal environment during critical periods of development can have effects on the brain that persist into adulthood.