Endometrial receptivity for embryo implantation in the rat is a transient state occurring on day 5 of pregnancy or pseudopregnancy and is controlled by estrogen and progesterone. To identify genes potentially involved in receptivity, a uterine cDNA library was screened. An interesting pattern for Cystatin C (Cst3) expression was discovered with a peak in abundance just prior to embryo implantation (day 4 of pregnancy) followed by a significant drop the following day when implantation is initiated. Histology localized Cst3 mRNA and CST3 protein to the glandular epithelium on day 4 of pregnancy suggesting that it is secreted into the uterine lumen at this time. In ovariectomized rats endometrial Cst3 mRNA levels decreased within 3 h of treatment with estradiol; this effect was inhibited by the anti-estrogen, ICI 182, 780. The data suggest that the endometrial expression of the cysteine protease inhibitor, Cst3, is modulated by estrogen during the peri-implantation period. (c) 2006 Elsevier Inc. All rights reserved.