Developmental Changes in Extracellular Matrix Messenger RNAs in the Mouse Placenta During the Second Half of Pregnancy: Possible Factors Involved in the Regulation of Placental Extracellular Matrix Expression1

Abstract

Expression of procollagens (Col1a1/2, Col3a1, Col4a1/2, Col5a1/2) and fibronectin 1 (Fn1) in the mouse fetal placental tissue was examined during the second half of pregnancy. Ribonuclease protection assays (RPAs) revealed that levels of these mRNAs noticeably increased between Days 10 and 14 of pregnancy, and they remained at relatively constant levels thereafter. In situ hyridization showed that Col1a1 and Col4a1 mainly localized in the labyrinth, whereas Fn1 was expressed mainly in the spongiotrophoblast. Since members of the transforming growth factor-beta (TGFB) superfamily are involved in the regulation of extracellular matrix (ECM) expression in various tissues, mRNA levels of TGFB family members and their binding proteins were also examined by RPAs. Transforming growth factor-beta1-3 (Tgfb1-3), activin subunits (Inhba, Inhbb), follistatin (Fst), and follistatin-like 3 (Fstl3) were expressed in the placenta, whereas significant expression of myostatin (Mstn) was not detected. Although the expression patterns of Tgfb1-3 and Inhba in the placenta suggest possible involvement of TGFBs and activin A in the regulation of placental ECM expression, neither TGFBs nor activin A affected ECM mRNA levels in vitro. On the other hand, hypoxia significantly decreased Col1a1/2 and Col4a1/2 mRNAs in cultured placental cells, and a high-glucose condition significantly increased Col1a1 and Col3a1 mRNAs. Fn1 expression was increased under the high-glucose condition, although hypoxia also increased Fn1 expression to a lesser degree. These data suggest that an increase in oxygen tension and nutrient supply during placentation rather than TGFB family members may be responsible for the increase in the placental ECM mRNA expression.