Expression of tissue inhibitor of metalloproteinase-4 (TIMP-4) in endometrium and placenta of rhesus monkey (Macaca mulatta) during early pregnancy.

The tissue inhibitors of metalloproteinases (TIMPs) are secreted as important regulators of the matrix metalloproteinases (MMPs). TIMP-4 is the most recently characterized member of the TIMPs family. In the present study, we examined the expression and localization of the TIMP-4 transcript and protein in endometrium and placenta of rhesus monkey (Macaca mulatta) on days 12, 18 and 26 of pregnancy using RT-PCR, in situ hybridization, and immunohistochemistry. The fragment of TIMP-4 gene from rhesus monkey uterine samples shared 95% identity with the corresponding region of human homologue. On day 12 of pregnancy, TIMP-4 mRNA was mainly expressed in the glandular and luminal epithelium. On days 18 and 26 of pregnancy, the expression of TIMP-4 mRNA tended to decline in glandular epithelium and there were strong staining in the placental villi. Furthermore, TIMP-4 mRNA was very faint or undetectable in the stromal cells, endothelial cells of arterioles and myometrium at any stages of pregnancy. The results of immunohistochemical analysis were similar to that of its mRNA. These findings indicate that TIMP-4 might play an important role in glandular secretion, endometrial tissue remodeling and invasion of the trophoblast cells by regulating MMPs in a localized manner in the uteri of rhesus monkey during early pregnancy.