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Mouse embryo implantationSuccessful implantation is critical for the development of the mammalian embryo. This process involves a controlled invasion of the uterine wall by the embryonic trophoblast. The resulting differentiation of the uterine stroma to decidua is thought to provide a barrier to invasion. The hypothesis tested by our lab is that the decidual extracellular matrix plays a major role in controlling invasion. Our previous work has focused on stromal matrix remodeling. demonstrating an upregulation of basement membrane molecules. Analysis of matrix receptors has shown that in contrast to the limited number of observed decidual receptors. trophoblast has multiple receptors for basement membrane molecules. including galactosyltransferase. a number integrin subunit combinations. and IKVAV and YIGSR receptors for laminin. Our current work is concentrating on proteinase synthesis. in both trophoblast invasion and decidua matrix remodeling. and the control provided by matrix composition and/or specific matrix receptors. The work uses a 3-dimensional in vitro gel invasion assay to study trophoblast invasion. The effects of decidual matrix molecules added to Vitrogen (collagen type I) based gels on the synthesis of metallo-. serine. and acidic cysteine proteinases. are studied using zymography. as well as western and northern blotting. Similar studies focus on the proteinases synthesized by uterine stromal cells during remodeling of vitrogen gels. Decidua is also thought to participate in invasion control by the secretion of proteinase inhibitors. We are also studying the production of cystatins. cathepsin inhibitors. during decidual differentiation in vivo and in vitro. Both cDNA probes and specific antibodies are used to study cystatin A and C at the transcription and protein levels. Selected PublicationsContractor T. Babiarz B. Kowalski AJ. Rittling SR. Sorensen ES. Denhardt DT. (2005) Osteoclasts resorb protein-free mineral (Osteologic discs) efficiently in the absence of osteopontin. In Vivo. 19(2):335-41. Afonso S. Tovar C. Romagnano L. Babiarz B. (2002) Control and expression of cystatin C by mouse decidual cultures. Mol Reprod Dev. 61(2):155-63. Afonso. S.. Tovar. C.. Romagnano. L.. and Babiarz. B. (2001) The control and expression of Cystatin C by mouse decidual cultures. (In Press - Molecular Reproduction and Development) Afonso. S.. Romagnano. L.. and Babiarz. B. (1999) Expression of Cathepsin proteinases by mouse trophoblast in vivo and in vitro. Developmental Dynamics 216:374-384. Babiarz. B.. Afonso. S.. and Romagnano. L. (1998) Cellular interactions and Cathepsin proteinases in mouse embryo implantation. Serono International Symposium. Embryo Implantation: Molecular. Cellular. and Clinical Aspects (DD Carson. editor). Springer-Verlag. NY. pp67-82. Afonso. S.. Romagnano. L.. and Babiarz. B (1997) The expression and function of Cystatin C and Cathepsins B and L during mouse embryo implantation and placentation. Development 124:3415-3425. |