Spatial analysis of placentae during congenital cytomegalovirus infection suggests distinct cellular profiles in immune and trophoblast cells: an exploratory study

Abstract

Human cytomegalovirus (CMV) is the leading infectious cause of congenital birth defects worldwide. The placenta is a major route of vertical transmission, and both immune and trophoblast cells are susceptible to CMV infection. This study aimed to spatially characterize gene and protein expression changes associated with CMV infection in the human placenta. In this exploratory study, CMV+ and control placentae were analyzed using the NanoString GeoMx Digital Spatial Profiler to assess compartment-specific transcriptomic and proteomic profiles in trophoblast and immune cell populations. CMV+ placentae showed increased immune activation in both trophoblast and immune cells, including pathways related to immune-cell proliferation, differentiation, lymphopoiesis, and T-cell development. Infected placentae also showed altered tissue repair and remodeling pathways, along with changes in proapoptotic proteins and cell death-associated transcripts. Given the limited sample size, these findings are descriptive and hypothesis-generating. They provide preliminary insight into CMV-associated placental immune dysregulation and identify candidate pathways for investigation in larger, prospective studies.