A reference atlas of human fetal membranes from mid-gestation to term

Human fetal membranes are barrier to shield the developing fetus from mechanical, immune and infection-related insults and therefore essential to sustain pregnancy. While their dysfunction results in preterm prelabor rupture of membranes (PPROM), limited knowledge about changes in their characteristics during development is currently available. Here, we present a single-nucleus RNA sequencing atlas of reflected amnion and chorion from midterm to term gestation, and we relate these to samples derived from preeclampsia and the immediate vicinity of placenta. Key findings include a broad downregulation of heat shock proteins besides the upregulation of pappalysins and the downregulation of insulin-like growth factor binding proteins, likely resulting in the increased availability of insulin-like growth factor (IGF-2) at term. Additionally, changes in extracellular matrix composition, reduction of canonical wingless/integrated (WNT) signaling, and diminished epithelial plasticity were observed. Cell–cell communication analyses revealed progressive immune remodeling, with maternal macrophages and natural killer cells shaping the signaling environment of the fetal membrane. While integration with first-trimester data demonstrates continuity of developmental programs, preeclampsia samples showed dysregulated maternal cells. This atlas provides a high-resolution reference for fetal membrane biology, offering insights into regulatory mechanisms underlying pregnancy maintenance, PPROM, and related complications.

• Type: RNASeq
• Archive: European Genome-phenome Archive (EGA)