Advanced Maternal Age Impairs Decidual Angiogenesis and Spiral Artery Remodelling

Abstract

Pregnancy presents an extreme physiological challenge that relies on rapid angiogenic vascular expansion and remodelling to establish the maternal-fetal vascular unit at the uteroplacental interface. These adaptations to the pregnancy-specific decidual vasculature are necessary for pregnancy progression. Advanced age pregnancies (AAP; pregnant person >35 years old) are associated with increased risk of poor pregnancy outcomes. Despite increasing evidence of the centrality of vascular aging in mediating organotypic dysfunction, whether vascular aging in the decidua occurs in the context of AAP is unknown. Using a murine model of AAP, we find that alongside embryonic developmental delay and deficient placental vascularization, AAP dams had impaired decidual angiogenesis and spiral artery remodeling with imbalances in both systemic and local uterine angiogenic factor expression in the VEGF and angiopoietin signalling families. These findings reveal that pregnancy may expose vascular aging mechanisms that contribute to declining reproductive success and increased cardiovascular risk later in life.