Investigating neurosteroids in pregnancy and their effect on perinatal outcomes: a study in spiny mice

Stillbirth and small for gestational age (SGA) remain major adverse, unresolved, and untreated outcomes of pregnancy. Global estimates indicate 1.9 million stillbirths occur annually, along with the birth of 23.4 million SGA babies that are at increased risk of long-term neurodevelopmental disability and even death. Although the causes of stillbirth and SGA are acknowledged to be multifactorial, new evidence points to abnormalities in neurosteroid modulation during pregnancy as a major contributor. The sources of the dysregulated neurosteroid production are unknown, as well as the mechanism of injury on fetal brain development and function. The global aim of this Honours/Masters project will be to investigate changes in neurosteroid levels across pregnancy and their influence on perinatal health using the spiny mouse. The levels of neurosteroids within the maternal circulation and their associated synthesising organ source will be characterised throughout spiny mice pregnancy. Using the knowledge gain from this characterisation, neurosteroid inhibition will be induced within the pregnant spiny mouse to assess its effect on both fetal and neonatal outcomes. This project will inform potential avenues for treatment therapies for stillbirth and SGA. This project will involve a multitude of laboratory-based research techniques, including small rodent experiments (handling, surgery, behaviour testing), molecular techniques (PCR, ELISA), bioinformatics (RNAseq) and histology (immunohistochemistry, immunofluorescence). The student will also have an opportunity to engage with international collaborators.