Fate of Hamster Oviductin in the Oviduct and Uterus During Early Gestation EMMANUELLE ROUX, 1 GILLES BLEAU, 1,2 AND FREDERICK W.K. KAN 1,3 * 1 Maisonneuve-Rosemont Hospital Research Center, Faculty of Medicine, University of Montreal, Montreal Quebec 2 Department of Obstetrics and Gynecology, Faculty of Medicine, University of Montreal, Montreal, Quebec 3 Department of Anatomy and Cell Biology, Faculty of Medicine, Queen’s University, Kingston, Ontario, Canada ABSTRACT Oviductins are a family of glyco- proteins which are synthesized and secreted by oviduc- tal secretory cells and which, upon their secretion in the lumen of the oviduct, become associated with postovu- latory oocytes and developing embryos. Recently, we showed that hamster oviductin is maximally secreted in the oviduct at the time of ovulation and is later associated with a certain population of uterine epithelial cells, where it is subsequently endocytosed and de- graded. In light of these results, this study was con- ducted to follow the fate of hamster oviductin in the oviduct and uterus during early gestation. Using a monoclonal antibody against hamster oviductin, immu- nofluorescence and immunogold labeling revealed that during early gestation, immunoreactivity to oviductin in the uterus gradually diminished to an almost total disappearance at time of implantation. However, the strong labeling intensity remained unchanged in the oviduct. Biochemical analyses demonstrated that a degradation of oviductin occurs in the uterus, and a loss of immunoreactivity was also observed as gesta- tion progressed, so that by the time of implantation, immunoreactivity to oviductin was barely detectable. The decrease of oviductin along the uterine epithelium at the time of blastocyst attachment and its final disappearance at implantation suggest that this glyco- protein could be a potential modulator of uterine receptivity. Mol. Reprod. Dev. 46:306–317, 1997. r 1997 Wiley-Liss, Inc. Key Words: oviductin; gestation; uterus; oviduct; embryo implantation; uterine receptivity; immunocyto- chemistry INTRODUCTION The mammalian oviduct synthesizes and secretes many proteins, among which are a family of glycopro- teins named oviductins. In many species, including the rabbit (Shapiro et al., 1974), sheep (Gandolfi et al., 1989), pig (Buhi et al., 1990, 1993), cow (Wegner and Killian, 1991), and baboon (Boice et al., 1990), ovi- ductins bind to the zona pellucida of postovulatory oocytes during their transit in the oviduct; this binding phenomenon is also shown in the hamster (Le ´veille ´ et al., 1987; Araki et al., 1987; Robitaille et al., 1988; Kan et al., 1988, 1989; Oikawa et al., 1988; Abe and Oikawa, 1990). Hamster oviductin is a mucin-like glycoprotein with polydispersion resulting from different glycosyla- tion patterns of its peptide core (Malette and Bleau, 1993). Maximally secreted in the oviduct around the time of ovulation (Roux and Kan, 1995), hamster oviductin is also found over the zona pellucida of developing embryos (Kan et al., 1993). It is internalized by the blastomeres (Kan et al., 1993), suggesting a possible role for hamster oviductin in embryonic devel- opment. A recent immunocytochemical study revealed that, after its secretion by oviductal secretory cells, hamster oviductin gains access to the uterus where it becomes associated with a certain population of uterine epithelial cells during the estrous cycle; oviductin is subsequently internalized and degraded by these cells (Roux et al., 1996). During early gestation, the uterus must have com- pleted the changes allowing nidation, in order to give rise to the ‘‘implantation window’’ (uterine receptivity) (Denker, 1993). The embryo must reach a certain degree of maturity in order to be competent to implant, and must be in the uterus at the right time correspond- ing to the phase of uterine receptivity (Psychoyos, 1986). Thus, implantation of the embryo in the uterus is restricted to certain conditions (i.e., an embryo can only invade a receptive uterus). However, trophoblast cells of implantation-stage blastocysts are able to implant at many ectopic sites, such as the anterior chamber of the eye (Rogers et al., 1988), the spleen (Kirby, 1963b), the kidney (Fawcett, 1950; Porter, 1967), and even the testis (Kirby, 1963a), while embryos can invade a nonreceptive uterus only if the epithelium is previously scraped (Cowell, 1969). The receptivity of the uterus to embryo implantation is under hormonal control: the uterus will be conditioned by ovarian hormones (Rog- ers, 1992; Weitlauf, 1994). Estrogens prepare the endo- metrium, and subsequently progesterone produced by the corpus luteum will permit nidation (Guillomot et al., 1991). The crucial state of uterine receptivity is Contract Grant sponsor: Medical Research Council of Canada; Con- tract Grant numbers: MT 10904 and MT 11684. *Correspondence to: Dr. Frederick W.K. Kan, Department ofAnatomy and Cell Biology, Faculty of Medicine, Queen’s University, Kingston, Ontario K7L 3N6, Canada. Received 13 December 1994; accepted 3 September 1996. MOLECULAR REPRODUCTION AND DEVELOPMENT 46:306–317 (1997) r 1997 WILEY-LISS, INC.