10 Maternal exposures and molecular regulation of the human placenta and endometrium

Abstract Abstract: Introduction The placenta mediates the effects of changing maternal environments during gestation on fetal development and on fetal and maternal lifelong health. These studies investigated the effects of exposures during pregnancy on human placental function, gene expression and epigenetics, and the subsequent associations with fetal development. Methods We use ex vivo systems including placental perfusion, villous and trophoblast culture, multi-scale imaging, epigenetic, proteomic and transcriptome analysis as well as placental samples from our Southampton cohorts. Results Findings include maternal vitamin D levels, smoking, and poor diet during pregnancy associate with placental gene expression of key nutrient transporters. These transporters relate to fetal and neonatal growth and body composition as well as maternal body composition. We show localized placental activation of vitamin D that induces rapid effects on the placental transcriptome, epigenome and proteome that effect placental function and thereby fetal development, independent of vitamin D transfer. Conclusions Local vitamin D metabolism may also impact upon the interplay at the maternal-fetal interface. The structure and molecular profile of the endometrium during the window of implantation is being investigated in relation to the maternal environment. Cell population profiles and interactions along with endometrial gland cilia function and extracellular vesicles production are targeted as potential biomarkers to predict pregnancy outcome. This work involves endometrial organoid culture, 3D imaging and single cell transcriptomic analysis. These data demonstrate a complex interplay between vitamin D and the placenta and endometrium and may inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy. (Supported by The Gerald Kerkut Trust, Wellbeing of Women, Wessex Medical Research, The Rosetree’s Trust)