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Placental endocrine function and materno-fetal resource allocation during pregnancy

Supervisor: Amanda Sferruzzi-Perri, Alison Forhead

During pregnancy nutrients must be supplied to the fetus for growth as well as to the mother to maintain the pregnancy. The placenta is central to this materno-fetal nutrient balance as it is responsible for substrate transfer to the fetus and secretes hormones into the mother with metabolic effects1,2. Failure to achieve this nutrient-balance leads to pregnancy complications for the mother and abnormal birthweight with long-term consequences for maternal and offspring health3. However, our understanding of the identity and role of placental endocrine mediators in materno-fetal resource allocation during pregnancy, and their importance for fetal growth, maternal health and offspring wellbeing, are limited. Thus one major aim of the laboratory is to identify the biological significance and nature of placental endocrine function in pregnancy success and long-term health. To address this fundamentally-important knowledge gap we use newly-developed mouse models where placental endocrine function is selectively modified and the latest sequencing techniques to comprehensively translate the dialogue between the placenta and mother. A PhD project could involve:

- Assessing the consequences of genetically-altered placental endocrine cells on maternal metabolic profile and fetal nutrient acquisition and growth

- Characterising the secretome of placental endocrine cells and identifying the function of secreted candidates

- Determining whether changes in maternal-fetal resource allocation due to altered placental endocrine function program ill health of the offspring and/or mother later in life

Depending on the project chosen, a PhD could employ cell-specific gene manipulation in mice, in vivo metabolic tests (glucose and insulin tolerance tests, hyperinsulinemic-euglycemic clamps), in situ functional assays (placental nutrient transport assays, mitochondrial respirometry), in vitro cell culture, histological (immunohistochemistry, stereology) and biochemical assays (enzyme assays) and molecular (RNAseq, qPCR, western blotting) and proteomic methodologies (mass spectrometry). For further details on what a specific rotation and PhD project would entail, please contact me directly.


Relevant references

Fowden, A. L., Forhead, A. J., Sferruzzi-Perri, A. N., Burton, G. J. & Vaughan, O. R. Endocrine regulation of placental phenotype. Placenta 36, S50-59, doi:10.1016/j.placenta.2014.11.018 (2014).

Sferruzzi-Perri, A. N., Vaughan, O. R., Forhead, A. J. & Fowden, A. L. Hormonal and nutritional drivers of intrauterine growth. Curr Opin Clin Nutr Metab Care 16, 298-309, doi:10.1097/MCO.0b013e32835e3643 (2013).

Sferruzzi-Perri, A. N. & Camm, E. J. The programming power of the placenta. Front Physiol 7:33, DOI: 10.3389/fphys.2016.00033 (2016).

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