Differential temporal and spatial expression of mRNA encoding extracellular matrix components in decidua during the peri-implantation period

Changes in the temporal and spatial patterns of expression of mRNA encoding uterine extracellular matrix (ECM) proteins were determined during the peri-implantation period. Northern blot hybridization of cDNAs corresponding to laminin (LM) B₁, LM B₂, entactin, fibronectin, collagen (CL) type IV α1, and CL IV α2 was performed on RNA extracted from either whole mouse uteri or endometrial explants between Day 4, i.e., the day of implantation, and Day 7 of pregnancy, when the decidual response is well established. These analyses revealed a dramatic increase in LM B₂, and CL IV α2 mRNA expression by Day 7 of pregnancy. Relative levels of the mRNA encoding other ECM components, including LM B₁, were not altered when compared to changes in the relative level of expression of glyceraldehyde-3- phosphate dehydrogenase mRNA. The differential expression of the B chains of LM appeared to be limited to the stromal cells of the endometrium. In situ hybridization of uterine sections with cRNA probes corresponding to LM B₁, LM B₂, and CL IV α1 demonstrated that LM B₁ was expressed temporally in high amounts in the primary decidual zones (PDZ) and persisted throughout PDZ degeneration. LM B₂ mRNA was expressed in both primary and secondary decidual zones and persisted through Day 8 of pregnancy. CL IV α1 mRNA expression mimicked that of LM B₂. Oviduct ligation on Day 2 of pregnancy was used to prevent embryo transport to one uterine horn, whereas decidualization and embryo implantation were permitted in the contralateral horn. This experiment demonstrated that the increases in uterine ECM mRNA expression were not due solely to the changing hormonal milieu of the uterus. ECM components, including CL IV, have been shown to bind growth factors such as transforming growth factor-β (TGF-β) in an insoluble but biologically active form. The remarkable similarity between the pattern of CL IV and LM B₂ expression and previously reported TGF-β deposition (Tamada et al., Mol Endocrinol 1990; 4:965-972) prompted examination of the effects of this growth factor on blastocyst development in vitro. TGF-β1 was tested for its ability to alter embryo outgrowth on LM-coated tissue culture surfaces; however, significant differences in the rate or extent of outgrowth in the presence of TGF-β were not detected. Collectively, these studies indicate that marked changes occur in both the temporal and regional patterns of expression of uterine ECM components, including differential expression of mRNA encoding LM subunits; however, TGF-β1 does not appear to directly influence embryo outgrowth on LM.