description): Blastocyst implantation occurs only if the uterus is in a state of receptivity. Recent studies have shown that the period of receptivity is preceded by a loss of cell surface mucin-type glycoproteins, including Muc-1 (mouse), suggesting that the loss of these mucins may act as blocking factors which contribute to the nonreceptive state. This proposal is based on the recent discovery that the apical cell surface of the endometrial epithelium in the rat is covered with a sialomucin complex (SMC) previously described in this laboratory. This complex, originally discovered in a rat mammary adenocarcinoma, is composed of a mucin subunit ASGP-1 and a transmembrane subunit ASGP-2. The latter has two EGF-like domains, one of which binds to the receptor tyrosine kinase ErbB-2/Neu. During pregnancy in the rat, the complex is lost coincident with the onset of the period of receptivity in a steroid hormone-dependent manner. In contrast to membrane Muc-1, SMC at the uterine surface is in a soluble form which lacks the transmembrane domain of ASGP-2. The first objective of this research will be to characterize the mechanisms by which the soluble form is produced and localized to the apical surface of the luminal epithelial cells of the rat endometrium. For these studies the investigators will use molecular biological, biochemical and immunological analyses. Although loss of mucins appears to contribute to the appearance of receptivity in the rodent, their role in the human is much less clear. The second objective will be to characterize the expression of SMC in the uterus of women at various stages of the menstrual cycle and of women with clinically-defined fertility problems. These studies will be done in collaboration with Dr. Daniel Carson of the M.D. Anderson Cancer Center, who is conducting similar studies on MUC1 (human). The overall goal is to understand how these cell surface mucins contribute to receptivity and whether they may be useful in the diagnosis and treatment of women with fertility problems.
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