PARENT SESSION

(13) PROGESTERONE AND INTERFERON TAU REGULATE CATHEPSIN L (CTSL) EXPRESSION IN THE ENDOMETRIAL EPITHELIUM OF THE OVINE UTERUS.

Song, Gwonhwa¹, Bazer, Fuller¹, Spencer, Thomas¹, ¹ Texas A&M University, College Station, TX

ABSTRACT- CTSL is a lysosomal acid cysteine protease that is primarily involved in intracellular protein catabolism and turnover, but can also be secreted. CTSL cleaves a wide range of substrates including extracellular matrix proteins (fibronectin, collagen, elastin, and laminin), serum proteins, cytoplasmic proteins, and nuclear proteins. This study determined effects of the estrous cycle (C), pregnancy (Px), progesterone (P4) and interferon tau (IFN) on CTSL gene expression in the ovine uterine endometrium. In Study One, CTSL mRNA was affected (P<0.05) by day, status (C or Px), and their interaction. In both C and P ewes, CTSL mRNA was low on Day 10 and increased about 4-fold to a maximum on Day 14. In C ewes, CTSL mRNA declined from Days 14 to 16, but increased about 2-fold from Days 14 to 18 in Px ewes. In the uterus, CTSL mRNA was abundant in the endometrial luminal epithelium (LE) and superficial glandular epithelium (sGE) and also in conceptus trophectoderm. In Study Two, cyclic ewes were ovariectomized and fitted with intrauterine (i.u.) catheters on Day 5 and hysterectomized on Day 17. Ewes received i.m. injections of 25 mg P4 from Days 5-16 or P4 and 75 mg ZK 136,317 (a P4 receptor antagonist) from Days 11-16. From Days 11-16, ewes also received i.u. injections of either control (CX) proteins (200 g) or recombinant ovine IFN (1x10⁸ antiviral units/day). Treatment with P4 induced CTSL mRNA in the endometrium (P4+CX vs P4+ZK+CX, P<0.001). In ewes receiving P4, IFN increased CTSL mRNA by about 3-fold (P4+CX vs P4+IFN, P<0.01), but not in ewes receiving P+ZK treatment (P4+IFN vs P4+ZK+IFN, P>0.10). CTSL mRNA was abundant in the endometrial LE/sGE of P4+CX and P4+IFN ewes, but was very low to undetectable in endometria of P+ZK treated ewes. Collectively, results support the hypothesis that CTSL gene expression in endometrial LE/sGE is induced by progesterone and stimulated by conceptus IFN. CTSL is one of three genes, including Wnt7a and galectin-15, now known to be stimulated by IFN in endometrial LE by an unknown non-classical signaling pathway that is independent of the classical Stat transcription factors. CTSL is likely involved in establishment of uterine receptivity to conceptus implantation. Supported by NIH HD32534.

KEY WORDS: cathepsin, pregnancy, implantation, Ovis aries