Matrix Metalloproteinases (MMP-2 and MMP-9) and Tissue Inhibitor-2 of Matrix Metalloproteinases (TIMP-2) in the Placenta and Interplacental Uterine Wall in Normal Cows and in Cattle with Retention of Fetal Membranes

Abstract

Matrixmetalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) play a key role in tissue re-modelling in the placenta. In the present study, distribution of MMP-2, MMP-9 and TIMP-2 was demonstrated immunohistochemically in the bovine placenta and interplacentomal tissue. Specimens representing the whole gestation until parturition were processed. Additionally, materials from cows with and without retention of fetal membranes were compared. MMP-2 expression was abundant in the maternal septae of the placentome in early gestation, with ongoing pregnancy immunoreactivity was restricted to the stromal tissue at the openings of maternal crypts. The chorionic epithelium opposite to these regions was also positive for MMP-2. MMP-9 expression was observed in the chorionic epithelium, except in the giant binucleate cells. In addition, the maternal epithelium and stroma showed immunoreactivity for MMP-9. No differences in MMP-2 and MMP-9 distribution could be observed between cows with proper release of fetal membranes and cows with retained fetal membranes. Giant binucleate cells expressed TIMP-2 during the whole gestation. Immunostaining for α-smooth muscle actin revealed contractile elements in the bovine placentome. Balance between proteolytic enzymes and their activators and inhibitors is essential for regular development of the placenta. The expression of TIMP-2 in the giant binucleate cells indicates an essential role of inhibitory factors during gestation. It is likely that less TIMP-2 is produced at the end of pregnancy as the number of binucleate cells is diminished.