Complications of pregnancy, such as recurrent pregnancy loss, pre-eclampsia, fetal growth restriction, and spontaneous preterm birth, affect ~20 % of human pregnancies, causing maternal and fetal morbidity and mortality. Although the molecular aetiology of these disorders is not well understood, they are thought to share a common pathogenesis, in insufficient uterine invasion by the placenta. Transposable elements (TEs) comprise 50 % of our genome and are increasingly recognised as important in human physiology and disease, contributing to genetic variation and species-specific gene expression patterns. Previously, we found that a subset of transposable elements that have been co-opted following previous viral infections, known as endogenous retroviruses (ERVs), exhibit regulatory potential in the human placenta. These ERVs feature active chromatin marks specifically in placenta, and were bound by transcription factors with key roles in placental development. These elements were almost all primate-specific, and altered placental gene expression. To test their function in more depth, we used CRISPR-Cas9 excisions to show that several ERVs act as enhancers for key genes in the human placenta, such as CSF1R, ENG and PSG5. Research is now underway to explore whether human genetic and epigenetic variation at ERVs may contribute to pregnancy complications, using samples of placenta from normal and complicated pregnancies, and human trophoblast organoids.
Physiology in Focus 2024 (Northumbria University, UK) (2024) Proc Physiol Soc 59, SA06
Research Symposium: Retroviral transposable elements and the pregnancy remodelling functions of human trophoblast
Jennifer Frost1, Miguel Branco1, Samuel Amante1, Hiroaki Okae1, Eleri Jones1, Jane Cleal1, Rohan Lewis1, Matthew Caley1, Takahiro Arima1, Rachel Tribe1, Lucilla Poston1, Michael Simpson1,
1Medical and Molecular Genetics, King’s College London, Guy’s Campus, Great Maze Pond, SE1 1UL London United Kingdom, 2Genomics and Child Health, The Blizard Institute, Queen Mary University of London, 4 Newark Street, E1 2AT London United Kingdom, 3Genomics and Child Health, The Blizard Institute, Queen Mary University of London, 4 Newark Street, E1 2AT London United Kingdom, 4Department of Trophoblast Research, Institute of Molecular Embryology and Genetics, Kumamoto University Kumamoto Japan, 5School of Human Development and Health, Faculty of Medicine, University of Southampton Southampton United Kingdom, 6Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine Sendai Japan, 7Women and Children's Health, King's College London, St Thomas' Hospital, Westminster Bridge Road London United Kingdom,
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