Crosstalk of villous cells in early placental development

In this study, we will investigate how human placental cells communicate with each other to ensure physiological development and function of the early human placenta. The human placenta is the connecting organ between the mother and the fetus. It has a tree-like structure consisting of a stromal core containing fetal blood vessels, immune cells and fibroblasts, and a surrounding cell layer, the trophoblasts. These trophoblasts are responsible for the maintenance of the pregnancy, transport of nutrients and gases from the mother to the baby, and also protect the fetus against harmful substances and pathogens. Of note, adverse pregnancy outcome such as miscarriages or compromised conditions referred to as great obstetrical syndromes (e.g.: preeclampsia, intrauterine growth restriction) have been causatively linked with deficient placentation. The placenta constantly changes its morphology in order to adapt to the rising demands of the growing fetus. Although placental structure and function during the second and third trimester of pregnancy are well documented, developmental and functional aspects in the very first weeks of gestation remain to be thoroughly addressed. However, it is considered that the communication between different placental cell types at early stages is crucial for the correct placental formation and function. My proposed research aims to understand the interaction and exchange of information between trophoblasts and stromal core cells ensuring proper human placental development. To address this aspect, I will utilise trophoblast organoids, comprising miniature placentae, and mix them with different stromal core cells in order to investigate their modes of communication. We propose that this approach will improve our understanding of physiological mechanisms and pathophysiological routes potentially being involved in early pregnancy loss or the development of pregnancy complications compromising the health and wellbeing of both, the mother and the baby.