Yes-Associated Protein 1 Coordinates the Morphogenesis of Uterine Lymphatic Vessels and Glands During Uterine Development

Abstract

Yes-associated protein 1 (YAP1), a core effector of the Hippo pathway, regulates organogenesis and tumourigenesis. However, its role in uterine lymphatic and glandular morphogenesis remains unclear. Frozen sections revealed the overall developmental pattern of uterine lymphatic vessels. The immunohistochemistry results from postnatal day 1 (P1) to P7 indicate that both blood and lymphatic vessels extend into the uterine muscle layer without glandular bud formation, accompanied by YAP1 mainly expressing in the cytoplasm of the uterus. From P8 to P10, the number of blood vessels and lymphatic vessels increases, glandular buds begin to form, and YAP1 nuclear expression rises. By P21, the tissue structure of the uterus resembles that of adults; YAP1 expression sharply decreases. By P28, YAP1 expression is nearly absent. We demonstrate that YAP1 expression dynamically shifts from cytoplasmic to nuclear localisation during postnatal uterine development in mice, correlating with lymphatic vessel invasion into the myometrium (P1–P10) and glandular maturation (P8–P21). Vascular development precedes lymphangiogenesis, suggesting angiogenesis-dependent nutrient delivery is critical for early uterine growth. These findings reveal YAP1 as a key coordinator of uterine morphogenesis, providing insights into gynaecological disorder mechanisms.