LIF AND PRL AND UTERINE PREPARATION FOR NIDATION

这项研究的长期目标是阐明 控制着床预定延迟的生理机制 食肉动物的胚胎滞育，表现出预定的延迟 植入时间为200+/-20天。总体论题是，改变 在子宫环境中是最终负责恢复的 胚胎发育。小鼠子宫上皮细胞分泌 白血病抑制因子(LIF)。LIF基因的缺失可防止 并导致小鼠胚胎滞育。管理 LIF对怀孕的LIF-雌性诱导新的胚胎发育和 植入。目前尚不清楚LIF在细胞周期调控中的作用。 在任何其他物种中植入；然而，人子宫LIF mRNA 在预测的植入时间，浓度最高。这个 拟议中的研究将检验LIF在 诱导恢复一个物种的胚胎发育和着床 表现出预定的植入延迟。前两个实验 将决定子宫LIF mRNA浓度是否在 植入时间以及催乳素(PRL)或卵巢类固醇是否会 提高子宫LIF基因表达水平。下一次实验将 确定125I-rhLIF是否会与子宫或胚泡结合。我们 将确定持续使用LIF是否会导致 在有休眠胚泡的雌性体内植入，就像在小鼠身上一样。 我们以前的研究已经证明，催乳素在 调节芥虫类食肉动物的植入。持续地给药 催乳素加速着床并刺激卵巢活动，如 黄体酮分泌增加。芥子科食肉动物的子宫也 拥有PRL结合位点。第二系列实验将测试 假设催乳素在子宫准备着床过程中起作用。 首先，我们将确定PRLR在子宫中的位置以及 子宫PRLr mRNA浓度在着床时升高。我们 然后尝试确定催乳素是否会改变子宫 环境：L)提高子宫孕酮浓度 受体，2)增加LIF与子宫的结合，或3)促进 子宫内膜腺的发育。

The long term objectives of this research are to elucidate the physiological mechanisms controlling obligate delay of implantation and embryonic diapause in a carnivore that exhibits an obligate delay of implantation lasting 200 +/- 20 days. The overall thesis is that changes in the uterine environment are ultimately responsible for resumption of embryonic development. The uterine epithelium of the mouse secretes leukemia inhibitory factor (LIF). Deletion of the gene for LIF prevents implantation and results in embryonic diapause in mice. Administration of LIF to pregnant LIF- females induces renewed embryonic development and implantation. Nothing is known about the role of LIF in the regulation of implantation in any other species; however, human uterine LIF mRNA concentrations are highest at the predicted time of implantation. The proposed research will test the hypothesis that LIF plays a role in inducing resumption of embryonic development and implantation in a species that exhibits obligate delay of implantation. The first two experiments will determine whether uterine LIF mRNA concentrations increase at the time of implantation and whether prolactin (PRL) or ovarian steroids will enhance uterine LIF mRNA concentrations. The next experiment will determine whether 125I-rhLIF will bind to the uterus or blastocysts. We will then determine whether constant administration of LIF will induce implantation in females with dormant blastocysts as it does in the mouse. Our previous studies have demonstrated that PRL plays a pivotal role in regulating implantation in mustelid carnivores. Constant administration of PRL hastens implantation and stimulates ovarian activity as indicated by increased progesterone secretion. The uterus of mustelid carnivores also possess PRL binding sites. A second series of experiments will test the hypothesis that PRL has a role in preparing the uterus for implantation. First we will determine the location of PRLr in the uterus and whether uterine PRLr mRNA concentrations increase at the time of implantation. We will then attempt to determine whether PRL might alter the uterine environment by: l) enhancing uterine concentration of progesterone receptors, 2) increasing uterine binding of LIF, or 3) promoting development of endometrial glands.