Follistatin-Like 3 (FSTL3) Gene Deletion Impairs Placental Development in Mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 389-405-Signaling Originating from Membrane Receptors
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-397
Rachel D Robertson, Waheed Mahmood, Imelda Mary McGonnell and Abir Mukherjee*
The Royal Veterinary College, London, United Kingdom
FSTL3 is an endogenous glycoprotein inhibitor of activin and related transforming growth factor-β (TGFβ) ligands. FSTL3, in turn, can be induced by activin, therefore leading to a mechanism for feedback inhibition of activin. FSTL3 is strongly induced in preeclamptic placenta; however, it is not clear how FSTL3 and activin action affect placental function both in health and disease. To identify the roles played by FSTL3 and the ligands it inhibits in physiology we have used a synexpression analysis strategy. By mining microarray RNA expression data we have identified a group of activin-responsive genes that have an expression pattern closely aligned to that of FSTL3. Our expression analyses support the possibility that FSTL3 action is important in cardiovascular tissues and potentially angiogenesis. To test the hypothesis that FSTL3 is indeed a regulator of angiogenesis we investigated whether the structure and function of the placenta, a tissue where FSTL3 is normally expressed at high levels, are altered in FSTL3 gene deleted mice (FSTL3 KO). Our findings reveal significant defects in the FSTL3 KO placenta when compared to WT. While gross morphology of the placenta is altered from flat to “domed” in shape in FSTL3 KO, there is also a significant increase in size at 16.5 and 18.5 dpc in FSTL3 KO compared to WT. Concomitantly, placental efficiency was significantly reduced at 18.5 dpc. Histological analyses and immunohistochemistry using mPL2, cytokeratin and desmin antibodies reveal alteration of placental structure in FSTL3 KO placenta compared to WT. In FSTL3 KO the spongiotrophoblast and labyrinth layers are irregular in shape and the labyrinth layer is reduced while the spongiotrophoblast layer is increased. Most importantly, the FSTL3 KO placenta has significantly reduced red blood cell amount strongly suggesting that FSTL3 action is crucial for circulation within the mouse placenta. Finally, using RT-PCR and immunofluorescence we find activin responsive FSTL3-synexpression genes are upregulated in FSTL3 KO placenta. Thus we conclude that FSTL3 action 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. Currently we are continuing our investigation of the molecular mechanisms by which increased activin action in the absence of FSTL3 lead to altered placental development.

Nothing to Disclose: RDR, WM, IMM, AM

*Please take note of The Endocrine Society's News Embargo Policy at

Sources of Research Support: Biotechnology and Biological Sciences Research Council, UK (BBSRC) research grant BB/J003727/1 support to AM and Wellcome Trust Research grant to IM