Transforming Growth Factor β Receptor Type 1 Is Essential for Female Reproductive Tract Integrity and Function

摘要: The transforming growth factor β (TGFβ) superfamily proteins are principle regulators of numerous biological functions. Although recent studies have gained tremendous insights into this family in female reproduction, the functions receptors vivo remain poorly defined. TGFβ type 1 receptor (TGFBR1), also known as activin receptor-like kinase 5, is major for ligands. Tgfbr1 null mice die embryonically, precluding functional characterization TGFBR1 postnatally. To study TGFBR1–mediated signaling we generated a mouse model with conditional knockout (cKO) reproductive tract using anti-Mullerian hormone 2 promoter-driven Cre recombinase. We found that cKO females sterile. However, unlike its role differentiation 9 (GDF9) vitro, seems to be dispensable GDF9 vivo. Strikingly, discovered develop oviductal diverticula, which impair embryo development and transit embryos uterus. Molecular analysis further demonstrated dysregulation several cell migration genes (e.g., Krt12, Ace2, MyoR) potentially associated development. Moreover, defective smooth muscle was revealed uteri mice. Thus, required integrity function, disruption leads catastrophic structural consequences oviduct