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LIF AND PRL AND UTERINE PREPARATION FOR NIDATION

LIF 和 PRL 以及子宫着床准备

基本信息

批准号：
2207773
负责人：
RODNEY A MEAD
金额：
$ 10.76万
依托单位：
UNIVERSITY OF IDAHO
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-05-01 至 2000-04-30
项目状态：
已结题

项目摘要

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.

本研究的长期目标是阐明控制专性着床延迟的生理机制，食肉动物的胚胎滞育，植入持续200 +/-20天。总的来说，在子宫环境中，最终负责恢复胚胎发育小鼠的子宫上皮分泌白血病抑制因子（LIF）。LIF基因的缺失植入并导致小鼠胚胎滞育。总局 LIF对妊娠LIF-雌性诱导更新的胚胎发育，置入目前还不清楚LIF在调节细胞凋亡中的作用。植入任何其他物种;然而，人子宫LIF mRNA 浓度在预测的植入时间最高。的拟议的研究将测试LIF在以下方面发挥作用的假设：在一个物种中诱导胚胎发育和植入的恢复表现出一定的植入延迟。前两个实验将确定子宫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增强子宫LIF mRNA浓度。下一个实验将确定125 I-rhLIF是否与子宫或胚泡结合。我们然后将确定持续给予LIF是否会诱导在具有休眠胚泡的雌性中植入，就像在小鼠中一样。我们以前的研究表明，PRL在调节鼬科食肉动物的着床。持续管理 PRL加速着床并刺激卵巢活性，如增加孕酮分泌。鼬科食肉动物的子宫具有PRL结合位点。第二个系列的实验将测试假设PRL在准备子宫着床中起作用。首先，我们将确定PRLr在子宫中的位置，子宫PRLr mRNA浓度在着床时增加。我们然后将试图确定PRL是否会改变子宫 l）增强子宫内孕酮的浓度受体，2）增加LIF的子宫结合，或3）促进子宫内膜腺体的发育。