Key regulatory pathways in recurrent pregnancy loss: Integrating trophoblast dysfunction, angiogenesis, and...

Recurrent pregnancy loss (RPL) is defined as two or more clinically confirmed pregnancy losses occurring before 20 weeks of gestation. It not only imposes severe psychological distress on women of childbearing age but also affects approximately 2.5% of individuals of reproductive potential. Although the etiology of RPL involves multiple aspects such as genetics, anatomy, immunity, and infections, more than 50% of cases remain unexplained, and their underlying pathogenesis has not been fully elucidated. Recent studies have indicated that trophoblast dysfunction, impaired placental angiogenesis, and dysregulated inflammatory responses at the maternal-fetal interface are key pathological processes involved in the development of RPL, with aberrant regulation of multiple signaling pathways playing a central role in these processes. This review systematically summarizes the current research progress on signaling pathways associated with RPL, focusing on three core dimensions: trophoblast function regulation, placental angiogenesis mechanisms, and inflammatory response balance. It provides an in-depth analysis of their roles and molecular mechanisms in the pathogenesis of RPL. By organizing the crosstalk and regulatory networks of these pathways, this review aims to offer a comprehensive reference for uncovering the complex etiology of RPL and lay a theoretical foundation for the development of precise diagnostic biomarkers and effective therapeutic strategies.