Journal
BIOLOGY OF REPRODUCTION
Volume 89, Issue 4, Pages -Publisher
SOC STUDY REPRODUCTION
DOI: 10.1095/biolreprod.112.106542
Keywords
decidualization; delayed implantation; embryo implantation; latent TGF-B1 complex; ovarian steroids; TGF-B1 activation
Categories
Funding
- Department of Science and Technology, New Delhi [SR/FT/LS-001/2008]
- Ministry of Health and Family Welfare, New Delhi
- CSIR, New Delhi [31/004(1091)/2011-EMR-I]
Ask authors/readers for more resources
Transforming growth factor-beta (TGF-B) plays an important role in embryo implantation; however, TGF-B requires liberation from its inactive latent forms (i. e., large latent TGF-B complex [LLC] and small latent TGF-B complex [SLC]) to its biologically active (i. e., monomer or dimer) forms in order to act on its receptors (TGF-BRs), which in turn activate SMAD2/ 3. Activation of TGF-B1 from its latent complexes in the uterus is not yet deciphered. We investigated uterine latent TGF-B1 complex and its biologically active form during implantation, decidualization, and delayed implantation. Our study, utilizing nonreducing SDS-PAGE followed by Western blotting and immunoblotting with TGF-B1, LTBP1, and latency-associated peptide, showed the presence of LLC and SLC in the uterine extracellular matrix and plasma membranous protein fraction during stages of the implantation period. A biologically active form of TGF-B1 (similar to 17-kDa monomer) was highly elevated in the uterine plasma membranous compartment at the peri-implantation stage (implantation and nonimplantation sites). Administration of hydroxychloroquine (an inhibitor of pro-TGF-B processing) at the preimplantation stage was able to block the liberation of biologically active TGF-B1 from its latent complex at the postimplantation stage; as a consequence, the number of implantation sites was reduced at Day 5 (1000 h), as was the number of fetuses at Day 13. The inhibition of TGF-B1 showed reduced levels of phosphorylated SMAD3. Further, the delayedimplantation mouse model showed progesterone and estradiol coordination to release the active TGF-B1 form from its latent complex in the receptive endometrium. This study demonstrates the importance of liberation of biologically active TGF-B1 during the implantation period and its regulation by estradiol.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available