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哺乳动物雷帕霉素靶蛋白(MTOR)的细胞信号机制:特定营养物质和分泌型磷蛋白 1 对哺乳动物胚胎发育的影响。

Mechanistic mammalian target of rapamycin (MTOR) cell signaling: effects of select nutrients and secreted phosphoprotein 1 on development of mammalian conceptuses.

机构信息

Center for Animal Biotechnology and Genomics and Department of Animal Science, Texas A&M University, College Station, TX, USA.

出版信息

Mol Cell Endocrinol. 2012 May 6;354(1-2):22-33. doi: 10.1016/j.mce.2011.08.026. Epub 2011 Sep 1.

DOI:10.1016/j.mce.2011.08.026
PMID:21907263
Abstract

Morphological differentiation of uterine glands in mammals is a postnatal event vulnerable to adverse effects of endocrine disruptors. Exposure of ewe lambs to a progestin from birth to postnatal day 56 prevents development of uterine glands and, as adults, the ewes are unable to exhibit estrous cycles or maintain pregnancy. Uterine epithelia secrete proteins and transport nutrients into the uterine lumen necessary for conceptus development, pregnancy recognition signaling and implantation, including arginine and secreted phosphoprotein 1 (SPP1). Arginine can be metabolized to nitric oxide and to polyamines or act directly to activate MTOR cell signaling to stimulate proliferation, migration, and mRNA translation in trophectoderm cells. SPP1 binds αvβ3 and α5β1 integrins and induces focal adhesion assembly, adhesion and migration of conceptus trophectoderm cells during implantation. Thus, arginine and SPP1 mediate growth, migration, cytoskeletal remodeling and adhesion of trophectoderm essential for pregnancy recognition signaling and implantation.

摘要

哺乳动物子宫腺的形态分化是一种产后事件,容易受到内分泌干扰物的不利影响。从出生到产后第 56 天,给羔羊注射孕激素可防止子宫腺的发育,成年母羊无法表现发情周期或维持妊娠。子宫上皮分泌蛋白质并将营养物质输送到子宫腔中,这对于胚胎发育、妊娠识别信号和着床是必要的,包括精氨酸和分泌型磷蛋白 1(SPP1)。精氨酸可以代谢为一氧化氮和多胺,或者直接作用激活 MTOR 细胞信号转导,刺激滋养外胚层细胞的增殖、迁移和 mRNA 翻译。SPP1 结合αvβ3 和 α5β1 整合素,诱导着床过程中胚胎滋养外胚层细胞的粘着斑形成、粘着和迁移。因此,精氨酸和 SPP1 介导滋养外胚层的生长、迁移、细胞骨架重塑和粘着,这对于妊娠识别信号和着床是必不可少的。

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