在白细胞介素-11受体α缺陷小鼠的蜕膜化缺陷过程中，子宫细胞外基质成分发生改变。
Uterine extracellular matrix components are altered during defective decidualization in interleukin-11 receptor alpha deficient mice.
作者信息
White Christine A, Robb Lorraine, Salamonsen Lois A
机构信息
Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia.
出版信息
Reprod Biol Endocrinol. 2004 Nov 10;2:76. doi: 10.1186/1477-7827-2-76.
BACKGROUND
Implantation of the embryo and successful pregnancy are dependent on the differentiation of endometrial stromal cells into decidual cells. Female interleukin-11 receptor alpha (IL-11Ralpha) deficient mice are infertile due to disrupted decidualization, suggesting a critical role for IL-11 and its target genes in implantation. The molecular targets of IL-11 in the uterus are unknown, but it is likely that IL-11 signaling modifies the expression of other genes important in decidualization. This study aimed to identify genes regulated by IL-11 during decidualization in mouse uterus, and to examine their expression and localization as an indication of functional significance during early pregnancy.
METHODS
Decidualization was artificially induced in pseudopregnant wild type (IL11Ra+/+) and IL-11Ralpha deficient (IL11Ra-/-) littermates by oil injection into the uterine lumen, and gene expression analyzed by NIA 15K cDNA microarray analysis at subsequent time points. Quantitative real-time RT-PCR was used as an alternative mRNA quantitation method and the expression and cellular localization of the protein products was examined by immunohistochemistry.
RESULTS
Among 15,247 DNA probes, 13 showed increased and 4 decreased expression in IL11Ra-/- uterus at 48 h of decidualization. These included 4 genes encoding extracellular matrix proteins; collagen III alpha1, secreted acidic cysteine-rich glycoprotein (SPARC), biglycan and nidogen-1 (entactin). Immunohistochemistry confirmed increased collagen III and biglycan protein expression in IL11Ra-/- uterus at this time. In both IL11Ra-/- and wild type uterus, collagen III and biglycan were primarily localized to the outer connective tissue and smooth muscle cells of the myometrium, with diffuse staining in the cytoplasm of decidualized stromal cells.
CONCLUSION
These data suggest that IL-11 regulates changes in the uterine extracellular matrix that are necessary for decidualization.
背景
胚胎着床与成功妊娠依赖于子宫内膜基质细胞分化为蜕膜细胞。雌性白细胞介素-11受体α（IL-11Rα）缺陷小鼠因蜕膜化受阻而不育，提示IL-11及其靶基因在着床过程中起关键作用。IL-11在子宫中的分子靶点尚不清楚，但IL-11信号传导可能会改变其他在蜕膜化中起重要作用的基因的表达。本研究旨在鉴定小鼠子宫蜕膜化过程中受IL-11调控的基因，并检测它们的表达及定位，以表明其在妊娠早期的功能意义。
方法
通过向子宫腔内注射油，在假孕的野生型（IL11Ra+/+）和IL-11Rα缺陷型（IL11Ra-/-）同窝小鼠中人工诱导蜕膜化，并在随后的时间点通过NIA 15K cDNA微阵列分析来分析基因表达。定量实时RT-PCR用作另一种mRNA定量方法，蛋白质产物的表达和细胞定位通过免疫组织化学进行检测。
结果
在15247个DNA探针中，有13个在蜕膜化48小时时在IL11Ra-/-子宫中表达增加，4个表达减少。其中包括4个编码细胞外基质蛋白的基因；胶原蛋白IIIα1、富含酸性半胱氨酸的分泌糖蛋白（SPARC）、双糖链蛋白聚糖和巢蛋白-1（内动蛋白）。免疫组织化学证实此时IL11Ra-/-子宫中胶原蛋白III和双糖链蛋白聚糖的蛋白表达增加。在IL11Ra-/-和野生型子宫中，胶原蛋白III和双糖链蛋白聚糖主要定位于子宫肌层的外层结缔组织和平滑肌细胞，在蜕膜化基质细胞的细胞质中呈弥漫性染色。
结论
这些数据表明IL-11调节子宫细胞外基质中对于蜕膜化所必需的变化。
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