| First Author | Li Q | Year | 2011 |
| Journal | PLoS Genet | Volume | 7 |
| Issue | 10 | Pages | e1002320 |
| PubMed ID | 22028666 | Mgi Jnum | J:177997 |
| Mgi Id | MGI:5296992 | Doi | 10.1371/journal.pgen.1002320 |
| Citation | Li Q, et al. (2011) Transforming Growth Factor beta Receptor Type 1 Is Essential for Female Reproductive Tract Integrity and Function. PLoS Genet 7(10):e1002320 |
| abstractText | The transforming growth factor beta (TGFbeta) superfamily proteins are principle regulators of numerous biological functions. Although recent studies have gained tremendous insights into this growth factor family in female reproduction, the functions of the receptors in vivo remain poorly defined. TGFbeta type 1 receptor (TGFBR1), also known as activin receptor-like kinase 5, is the major type 1 receptor for TGFbeta ligands. Tgfbr1 null mice die embryonically, precluding functional characterization of TGFBR1 postnatally. To study TGFBR1-mediated signaling in female reproduction, we generated a mouse model with conditional knockout (cKO) of Tgfbr1 in the female reproductive tract using anti-Mullerian hormone receptor type 2 promoter-driven Cre recombinase. We found that Tgfbr1 cKO females are sterile. However, unlike its role in growth differentiation factor 9 (GDF9) signaling in vitro, TGFBR1 seems to be dispensable for GDF9 signaling in vivo. Strikingly, we discovered that the Tgfbr1 cKO females develop oviductal diverticula, which impair embryo development and transit of embryos to the uterus. Molecular analysis further demonstrated the dysregulation of several cell differentiation and migration genes (e.g., Krt12, Ace2, and MyoR) that are potentially associated with female reproductive tract development. Moreover, defective smooth muscle development was also revealed in the uteri of the Tgfbr1 cKO mice. Thus, TGFBR1 is required for female reproductive tract integrity and function, and disruption of TGFBR1-mediated signaling leads to catastrophic structural and functional consequences in the oviduct and uterus. |
