Hamster: a unique model for studying implantation

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DESCRIPTION (provided by applicant): Ovarian progesterone is essential for implantation in all species studied. However, the requirement of embryonic estrogen in this process is still an unsettled issue, except in mice and rats in which embryos do not possess the machinery for estrogen synthesis. Implantation can occur in several species including hamsters and perhaps in humans in the absence of ovarian estrogen if progesterone is provided. However, our recent study shows that: (1) estrogen, but not progesterone, regulates the uterine expression of heparin binding EGF-like growth factor gene (Hegfl) in ovariectomized hamsters, and (2) Hegfl expression occurs in the uterine luminal epithelium surrounding the blastocyst at the time of implantation in the absence of circulating estrogen in progesterone-primed hypophysectomized pregnant hamsters. These results suggest that hamster blastocysts could be an alternative source of estrogen that acts locally to induce Hegfl gene expression in the uterus. Indeed, our preliminary experiments suggest the presence of cytochrome P450 aromatase protein in hamster morulae and blastocysts. Furthermore, the exposure of hamster morulae to a steroidal cytochrome P450 aromatase inhibitor in culture significantly inhibits the formation of blastocysts. These observations together with our preliminary results of estrogen receptor-alpha expression in preimplantation hamster embryos and uterus at the time of implantation led us to postulate that this species does not depend on ovarian estrogen, but requires embryonic estrogen to initiate embryonic and uterine changes required for implantation. However, neither the synthesis nor the role of embryonic estrogen in blastocyst formation, uterine receptivity and implantation in hamsters has been resolved. Thus, our specific aims to study in hamsters: (1) Do hamster preimplantation embryos produce estrogen? (2) Is embryonic estrogen required for morula-blastocyst transformation? (3) Is embryonic estrogen required for the establishment of uterine receptivity for implantation? (4) Does systemic estrogen induce uterine receptivity and implantation in the absence of embryonic estrogen? We will use multiple approaches including RT-PCR, in situ hybridization, immunohistochemistry, immunofluorescence, Western blotting, embryo culture and transfer and others to accomplish our goals. With better understanding of the mechanisms of embryo development and uterine receptivity for implantation, issues concerning fertility and infertility in women will be more effectively managed.