Endocrine Abstracts

Follistatin-like 3 (FSTL3) is an endogenous glycoprotein inhibitor of transforming growth factor-β (TGFβ) ligands such as activin. TGFβ ligands are integral to key cellular processes such as proliferation, development and differentiation, including angiogenesis. It is not clear, however, how FSTL3 and activin action affect tissue and organ functions in health and disease. We have identified a group of activin-responsive genes that have an expression pattern closely aligned to that of FSTL3 and our expression analyses support the likelihood that FSTL3 action is important in cardiovascular tissues and potentially angiogenesis. To test the hypothesis that FSTL3 is indeed a regulator of angiogenesis we studied the placenta in FSTL3 gene deleted mice (FSTL3 KO). Our findings reveal significant defects in the FSTL3 KO placenta when compared to WT. Gross overall analysis showed a significant increase in size at 16.5 and 18.5 dpc compared to WT. Concomitantly, placental efficiency was significantly reduced at 18.5 dpc. While gross morphology is altered from flat to domed in shape, histology and immunohistochemistry reveal morphological differences in placental junctional zones in FSTL3 KO placenta compared to WT. Most strikingly, the FSTL3 KO placenta has significantly reduced red blood cell amount strongly supportive of a role for FSTL3 in angiogenesis. Finally, activin responsive FSTL3-synexpression genes are upregulated in FSTL3 KO placenta. Thus we conclude that FSTL3 function is crucial for normal placental development and function and that the FSTL3 synexpression genes identified might contribute to an activin-responsive effector network important in normal placental development.