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The effects of abnormal folate metabolism on placenta form and function

The effects of abnormal folate metabolism on placenta form and function

 

Co-supervisors: Dr Erica Watson and Dr Margherita Turco

Dept of Physiology, Development and Neuroscience

 

For decades, it has been widely acknowledged that maternal folate (also known as folic acid) deficiency increases fetal risk of neural tube defects (NTDs). However, it is less publicized that folate deficiency in humans increases the risk for intrauterine growth restriction and defects in placentation might be involved. Abnormal development and function of the placenta can have detrimental effects on the fetus, from embryonic lethality and growth restriction to an increased disease risk later in life. Identifying how trophoblast cell differentiation and placenta development is affected by folate deficiency will greatly impact our understanding of the role that folate metabolism plays during development. This PhD project will explore the role of folate metabolism during trophoblast stem cell maintenance and differentiation using in vitro and in vivo models, with focus on the Mtrrgt mouse model of abnormal folate metabolism. The student will be involved in the derivation of mouse trophoblast stem cell lines, organoid co-culture, and metabolic and placental phenotype analysis in vivo. 

 

Contact: edw23@cam.ac.uk

 

Relevant references:

Padmanabhan N, et al., 2013. Mutation in folate metabolism causes epigenetic instability and transgenerational effects on development. Cell 155(1): 81-93.

Elmore CL, et al., 2007. Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase. Mol Genet Metab 90(5): 85-97.

Cherukad J, et al., 2012. Spatial and temporal expression of folate transporters and metabolic enzymes during mouse placental development. Placenta 33(5): 440-8.

Turco MY, et al., 2017. Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium. Nat Cell Biol 19(5):568-577.