UBC Theses and Dissertations
Adamts expression in the human decidua of early pregnancy Ng, York Hunt
The spatio-temporal expression of interleukin (IL)-1β and transforming growth factor (TGF)- β1 in the human endometrium suggests that these two cytokines act in concert with gonadal steroids to create a uterine environment that is capable of supporting a viable pregnancy. The highly regulated series of developmental events that culminates in the terminal differentiation of the stromal cells into deciduas in preparation for implantation is mediated by alterations in the composition of the endometrial extracellular matrix (ECM). Consequently, matrix metalloproteinases have been assigned central roles in implantation and placentation. I hypothesized that members of a novel family of metalloproteinases, the ADAMTS, may mediate certain proteolytic events that are operative at the maternal-fetal interface. A comprehensive survey of the ADAMTS subtypes present in first trimester human decidual tissue was performed. In addition, I have examined the ability of IL-1β and TGF-β1 to regulate the mRNA and protein levels of one of these endometrial ADAMTS subtypes, ADAMTS-1, in primary cultures of stromal cells isolated from first trimester decidua. The mRNA transcripts encoding ADAMTS-1, -2, -3, -4, -5 (-11), -6, -7, -8, -9, -10 and -12 are present in first trimester human deciduas. ADAMTS-1 mRNA transcript and protein expression were detected in all of the decidual stromal cell cultures using quantitative-competitive-polymerase chain reaction (QC-PCR) and Western blotting strategies. IL-βl (0-1000 IU) increased ADAMTS-1 mRNA and protein levels in decidual stromal cell cultures in a dosedependent manner. Significantly increased ADAMTS-1 mRNA and protein levels were also detected in cells cultured for 24 hours in the presence of a fixed amount of IL-1β (100 IU), with maximum levels being observed after 48 hours. In contrast, increasing concentrations of TGF-β1 (0-10 ng) decreased ADAMTS-1 mRNA and protein levels in these cells in a dose-dependent manner. Furthermore, a fixed concentration of TGF-β1 (5 ng) effected a significant time-dependent decrease in ADAMTS-1 mRNA and protein levels in decidual stromal cells that was readily apparent at 24 hours and continued to decline until the study was terminated at 48 hours. Collectively, these studies indicate that IL-1β and TGF-β1 have differential effects on ADAMTS-1 mRNA and protein levels in decidual stromal cells in vitro. These results suggest that cytokine-mediated regulation of ADAMTS-1 expression, and potentially of other ADAMTS family members, may be important in stromal cell differentiation that is essential for decidual function during early pregnancy.
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