Cathepsins in the ovine uterus: regulation by pregnancy, progesterone, and interferon tau.

Cathepsins (CTS) are peptidases that have biological roles in degrading extracellular matrix, catabolism of intracellular proteins, and processing of prohormones. Expression of CTSB, CTSD, CTSH, CTSK, CTSL, CTSS, and CTSZ genes was detected in the endometria of cyclic and early pregnant ewes with distinct temporal and spatial expression patterns. In the d 18 and 20 conceptus, expression of CTSB, CTSD, CTSL, and CTSZ mRNA was detected in the trophectoderm. Of particular note, CTSL mRNA was the most abundant CTS mRNA in the ovine endometrium and detected only in the luminal epithelium and superficial glandular epithelium of cyclic and pregnant ewes. CTSL mRNA increased 8-fold between d 10 and 18 in endometria of pregnant ewes, whereas it declined between d 14 and 16 in cyclic ewes. CTSL protein was also detected in conceptus trophectoderm, and pro-CTSL was detected in uterine flushings from ewes between d 12 and 16 of pregnancy. In ovariectomized and catheterized ewes, CTSL mRNA in the endometrium was increased by progesterone and intrauterine injections of ovine interferon (IFN)tau. Other endometrial CTS genes were also regulated by progesterone alone (CTSB, CTSK, CTSS, and CTSZ) or progesterone and IFNtau (CTSH, CTSK, CTSS, and CTSZ). These results indicate that CTS of endometrial and conceptus origin may regulate endometrial remodeling and conceptus implantation, endometrial CTS genes are regulated by ovarian and placental hormones, and CTSL is a novel IFNtau-stimulated gene expressed only in luminal epithelium and superficial glandular epithelium of the endometrium.