| First Author | Gao Y | Year | 2014 |
| Journal | Mol Endocrinol | Volume | 28 |
| Issue | 3 | Pages | 380-94 |
| PubMed ID | 24506537 | Mgi Jnum | J:212993 |
| Mgi Id | MGI:5582668 | Doi | 10.1210/me.2013-1284 |
| Citation | Gao Y, et al. (2014) TGFBR1 is required for mouse myometrial development. Mol Endocrinol 28(3):380-94 |
| abstractText | The smooth muscle layer of the uterus (ie, myometrium) is critical for a successful pregnancy and labor. We have shown that the conditional deletion of TGFbeta type 1 receptor (TGFBR1) in the female reproductive tract leads to remarkable smooth muscle defects. This study was aimed at defining the cellular and molecular basis of the myometrial defects. We found that TGFBR1 is required for myometrial configuration and formation during early postnatal uterine development. Despite the well-established role of TGFbeta signaling in vascular smooth muscle cell differentiation, the majority of smooth muscle genes were expressed in Tgfbr1 conditional knockout (cKO) uteri at similar levels as controls during postnatal uterine development, coinciding with the presence but abnormal distribution of proteins for select smooth muscle markers. Importantly, the uteri of these mice had impaired synthesis of key extracellular matrix proteins and dysregulated expression of platelet-derived growth factors. Furthermore, platelet-derived growth factors induced the migration of uterine stromal cells from both control and Tgfbr1 cKO mice in vitro. Our results suggest that the myometrial defects in Tgfbr1 cKO mice may not directly arise from an intrinsic deficiency in uterine smooth muscle cell differentiation but are linked to the impaired production of key extracellular matrix components and abnormal uterine cell migration during a critical time window of postnatal uterine development. These findings will potentially aid in the design of novel therapies for reproductive disorders associated with myometrial defects. |
