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Centre for Trophoblast Research

 

Research

The focus of my research is in understanding the mechanisms that cause fetal growth restriction and drive fetal programming of adult disease.

The fetus is entirely dependent upon a healthy, functional placenta to deliver sufficient nutrients to support normal growth. Fetal growth restriction (FGR), which describes a fetus that fails to achieve its genetic growth potential, affects approximately 10% of pregnancies in developed countries. Although the precise mechanisms are often unclear, FGR is frequently attributed to “placental insufficiency”, where the placental supply of nutrients fails to meet fetal demand. 

Placental insufficiency typically results in asymmetric growth restriction, with brain growth spared at the expense of other organs such as the liver, and rapid catch-up growth observed in the first year. In addition to increased morbidity and mortality in the neonatal period, FGR is associated with an increased risk of developing metabolic diseases such as type 2 diabetes and obesity in adulthood. However, the mechanisms that drive this “fetal programming” of adult disease are poorly understood.

In humans, increased expression of the imprinted gene PHLDA2 is associated with FGR. My research uses mouse models in which expression of Phlda2 is either increased or knocked-out in order to understand how Phlda2 regulates placental development, function, and ultimately, fetal growth. I am currently investigating how placental nutrient transport is affected in the context of elevated Phlda2 expression.

 

Funding

Centre for Trophoblast Research

Society for Endocrinology

Isaac Newton Trust

Publications

Key publications: 

Research articles

  • George A.G. Roberts and Simon J. Tunster, Characterising the dynamics of placental glycogen stores in the mouse. Placenta 99 (2020) 131-140.
  • Bethany R. L. Aykroyd, Simon J. Tunster and Amanda N. Sferruzzi-Perri, Igf2 deletion affects the endocrine capacity of the mouse placenta in a sexually dimorphic manner. J. Endocrinol 246(1) (2020) 93-108
  • A.P. Sowton, N. Padmanabhan, S.J. Tunster, B.D. McNally, A. Murgia, A. Yusuf, J.L. Griffin, A.J. Murray, E.D. Watson, Mtrr hypomorphic mutation alters liver morphology, metabolism and fuel storage in mice, Mol Genet Metab Rep 23 (2020) 10058
  • K. Menelaou, M. Prater, S. Tunster, G. Blake, C. Geary Joo, J.C. Cross, R. Hamilton, E. Watson, Blastocyst transfer in mice alters the placental transcriptome and growth, Reproduction 159(2) (2020) 115-132.
  • S.J. Millership, S.J. Tunster, M. Van De Pette, A.I. Choudhury, E.E. Irvine, M. Christian, R.M. John, J. Scott and D.J. Withers. Neuronatin deficiency causes neonatal growth restriction and adult obesity. Molecular Metabolism (2018).
  • S.J. Tunster, R. Boque-Sastre, G.I. McNamara, S.M. Hunter, H.D. Creeth, R.M. John. Sexually dimorphic response of the placenta to paternal loss of expression of Peg3. Frontiers in Cell and Developmental Biology (2018).
  • M. Van de Pette, S.J. Tunster, R.M. John, Loss of Imprinting of Cdkn1c Protects against Age and Diet-Induced Obesity, Int J Mol Sci 19(9) (2018).
  • S.J. Tunster, M. Van de Pette, H.D.J. Creeth, L. Lefebvre, R.M. John, Fetal growth restriction in a genetic model of sporadic Beckwith-Wiedemann Syndrome. Dis Model Mech (2018)
  • H.D.J. Creeth, G.I. McNamara, S.J. Tunster, R. Boque-Sastre, B. Allen, L. Sumption, J.B. Eddy, A.R. Isles, R.M. John. Maternal care boosted by paternal imprinting in mammals. PLoS Biol 16(7) (2018) e2006599.
  • Simon James Tunster, Genetic sex determination of mice by simplex PCR. Biology of Sex Differences. 8:31 (2017).
  • C. Duval, M.R. Dilworth, S.J. Tunster, S.J. Kimber, J.D. Glazier, PTHrP is essential for normal morphogenetic and functional development of the murine placenta, Dev Biol 430(2) (2017) 325-336.
  • S.J. Tunster, G.I. McNamara, H.D. Creeth, R.M. John, Increased dosage of the imprinted Ascl2 gene restrains two key endocrine lineages of the mouse placenta, Dev Biol 418(1) (2016) 55-65.
  • A.B. Janssen, L.E. Capron, K. O'Donnell, S.J. Tunster, P.G. Ramchandani, A.E. Heazell, V. Glover, R.M. John, Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3, Psychol Med 46(14) (2016) 2999-3011.
  • M. Van De Pette, S.J. Tunster, G.I. McNamara, T. Shelkovnikova, S. Millership, L. Benson, S. Peirson, M. Christian, A. Vidal-Puig, R.M. John, Cdkn1c Boosts the Development of Brown Adipose Tissue in a Murine Model of Silver Russell Syndrome, PLoS Genet 12(3) (2016) e1005916.
  • A.B. Janssen, S.J. Tunster, A.E. Heazell, R.M. John, Placental PHLDA2 expression is increased in cases of fetal growth restriction following reduced fetal movements, BMC Med Genet 17 (2016) 17.
  • S.J. Tunster, H.D. Creeth, R.M. John, The imprinted Phlda2 gene modulates a major endocrine compartment of the placenta to regulate placental demands for maternal resources, Dev Biol  (2015).
  • A.B. Janssen, S.J. Tunster, N. Savory, A. Holmes, J. Beasley, S.A. Parveen, R.J. Penketh, R.M. John, Placental expression of imprinted genes varies with sampling site and mode of delivery, Placenta 36(8) (2015) 790-5.
  • S.J. Tunster, M. Van De Pette, R.M. John, Isolating the role of elevated Phlda2 in asymmetric late fetal growth restriction in mice, Dis Model Mech 7(10) (2014) 1185-91.
  • S.J. Tunster, M. Van de Pette, R.M. John, Impact of genetic background on placental glycogen storage in mice, Placenta 33(2) (2012) 124-7.
  • K.R. Reed, S.J. Tunster, M. Young, A. Carrico, R.M. John, A.R. Clarke, Entopic overexpression of Ascl2 does not accelerate tumourigenesis in ApcMin mice, Gut  (2012).
  • S.J. Tunster, M. Van de Pette, R.M. John, Fetal overgrowth in the Cdkn1c mouse model of Beckwith-Wiedemann syndrome, Dis Model Mech 4(6) (2011) 814-21.
  • S.J. Tunster, B. Tycko, R.M. John, The imprinted Phlda2 gene regulates extraembryonic energy stores, Mol Cell Biol 30(1) (2010) 295-306.
  • M.D. Wood, H. Hiura, S. Tunster, T. Arima, J.Y. Shin, M. Higgins, R.M. John, Autonomous silencing of the imprinted Cdkn1c gene in stem cells, Epigenetics 5(3) (2010).
  • S.C. Andrews, M.D. Wood, S.J. Tunster, S.C. Barton, M.A. Surani, R.M. John, Cdkn1c (p57Kip2) is the major regulator of embryonic growth within its imprinted domain on mouse distal chromosome 7, BMC Dev Biol 7 (2007) 53.

Review articles

  • S. Tunster, E. Watson, A. Fowden, G.J. Burton, Placental glycogen stores and fetal growth: insights from genetic mouse models, Reproduction (2020)
  • A.B. Jensen, S.J. Tunster, R.M. John, The significance of elevated placental PHLDA2 in human growth restricted pregnancies, Placenta 35(8) (2014) 528-32.
  • S.J. Tunster, A.B. Jensen, R.M. John, Imprinted genes in mouse placental development and the regulation of fetal energy stores, Reproduction 145(5) (2013) R117-37.
  • S.J. Tunster, M. Van De Pette, R.M. John, BACs as Tools for the Study of Genomic Imprinting, J Biomed Biotechnol 2011 (2011) 283013.
2016 Next Generation Fellow
 Simon  Tunster

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