Program > Browse abstracts by author > Lewis Rohan

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, through their capacity to quickly generate genetic variation and influence host gene regulation, may contribute to species-specific placental gene expression, and processes such as placental invasion. Previously, we have shown that multiple endogenous retrovirus (ERV) families exhibit regulatory potential in placenta. These largely primate-specific elements are bound by transcription factors with key roles in placental development, and we used CRISPR-Cas9 excisions to show that several ERVs act as enhancers for genes that are important for placental function, 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.