The role of PAF in the establishment of pregnancy
The role of PAF in the establishment of pregnancy
批准号:
nhmrc : 107237
负责人:
Prof Christopher O'Neill
金额:
$24.12万
依托单位国家:
澳大利亚
项目类别:
NHMRC Project Grants
财政年份:
2000
资助国家:
澳大利亚
项目状态:
已结题
起止时间:
2000-01-01 至 2002-12-31
中文摘要
荷尔蒙是调节身体正常功能的基本化学信使。生殖尤其受到荷尔蒙的广泛影响。早期胚胎的发育及其植入子宫的机制还不是很清楚。这一过程中涉及到一种新的荷尔蒙。这种被称为血小板激活因子(或PAF)的激素在激素中是特殊的,因为它属于一种被称为磷脂的化学物质。这是相当罕见的。这种荷尔蒙可以以一种明显相互矛盾的方式起作用。它由胚胎产生,使其能够对胚胎起反作用,刺激胚胎生长和存活。然后,(某些物种的)胚胎会释放其他荷尔蒙,以阻止PAF作用于子宫。如果对PAF的子宫反应没有发生这种抑制,则PAF作用于子宫以阻止妊娠的进一步进展(黄体溶解)。荷尔蒙通过称为受体的特殊细胞蛋白作用于细胞。似乎PAF在胚胎和子宫中的受体不同,因此可能导致这两种组织触发不同的细胞反应。我们可以利用突变来阻止这两种可能的受体功能的老鼠。具有这些突变的小鼠的怀孕过程和胚胎发育将被研究,以此作为确定PAF在怀孕期间的作用的一种手段。将对胚胎进行详细研究,以确定PAF通过其受体作用于胚胎所引起的变化的性质。其中一个受体是一种全新的分子,以前并不被理解为能够作为细胞信号装置。这项研究将描述这种潜在的新受体是否以及如何在胚胎中发挥作用,使未来能够详细研究它在正常细胞功能中的作用。它将展示这种单一的激素如何同时调节子宫和胚胎,从而在怀孕的建立中起到相互矛盾的作用。
英文摘要
Hormones are essential chemical messengers that regulate the normal functions of the body. Reproduction in particular is widely influenced by hormones. The development of the very early embryo and its implantation into the uterus is not well understood. A new class of hormone has been implicated in this process. This hormone, known as platelet-activating factor (or PAF) is special among hormones since it belongs to a class of chemicals known as phospholipids. This is quite uncommon. This hormone can act in an apparently contradictory fashion. Its production by the embryo allows it to act back on the embryo to stimulate embryo growth and survival. The embryo (of some species) then releases other hormones which prevents the PAF from acting on the uterus. If this repression of the uterine response to PAF does not occur then PAF acts on the uterus to stop further progression of the pregnancy (luteolysis). Hormones act on cells via special cell proteins known as receptors. It seems that the receptor for PAF in the embryo and the uterus are different and may therefore result in triggering different cellular responses by these 2 tissues. We have available to us mice with mutations that stop the functioning of these two likely classes of receptors. The progress of pregnancy and the development of embryos in mice with these mutations will be studied as a means of defining how PAF acts in pregnancy. The embryo will be studied in detail to determine the nature of the changes induced within the embryo by PAF acting via its receptor. One of these receptors is an entirely new class of molecules not previously understood to be able to act as a cell signalling devise. This study will describe if and how this potential new receptor acts in the embryo, allowing future detailed investigation of its role in normal cell function. It will show how this single hormone can regulate both the uterus and embryo to have contradictory roles in the establishment of pregnancy.
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依托单位:
Development of a non-invasive diagnostic test of Embryo Viability
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Mechanisms of p53 induced embryopathy after in vitro fertilisation.
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The role of transcription factors in regulating the first round of gene expression in the early embryo.
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Characterisation of a signal transduction pathway in the early embryo
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