Abstract

Neuroplacentology is a term coined to describe an emerging area of placental research that aims to understand the impact of placental function on the developing brain. Links between placental dysfunction or pathology have been linked to abnormal neurodevelopment, including autism, but the causal mechanisms remain largely unknown. Many events including infection, malnutrition, and genetic abnormalities can disrupt placental function, or – as in preterm birth – can abruptly change the hormonal environment of the developing brain. Our research takes a multi-faceted approach to understanding these placental mechanisms by developing systems in which we can test specific hormonal loss and interventions. In this talk, I will describe our investigations of allopregnanolone (ALLO), a non-glucocorticoid progesterone derivative made by the placenta in both mouse and humans, that acts as a positive modulator of GABA A receptor activity. To directly test the role of placental ALLO, we generated a novel mouse model in which the gene encoding the synthetic enzyme for ALLO (Akr1c14) was specifically deleted in trophoblasts. Targeted placental ALLO loss led to permanent changes in offspring brain structure in a sex and regionally-specific manner. Our studies reveal new roles for a placental hormone in specific, long-term anatomical and behavioural changes. We suggest that identifying placental hormone insufficiency or augmenting key hormones after preterm birth might offer novel therapeutic opportunities to modify neurodevelopmental outcomes linked to poor placental function or preterm birth.