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首页> 外文期刊>The Journal of toxicological sciences >Altered gene expression profile in ovarian follicle in rats treated with indomethacin and RU486
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Altered gene expression profile in ovarian follicle in rats treated with indomethacin and RU486

机译:消炎痛和RU486处理的大鼠卵巢卵泡基因表达谱的改变

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It is well-known that indomethacin (the cyclooxygenase 1 & 2 inhibitor) and RU486 (or mifepristone, the progesterone receptor antagonist) block follicular rupture in rats. To characterize genetic alterations in unruptured follicles, gene expression profiles in ovarian follicle were analyzed in indomethacin- and RU486-treated female Sprague-Dawley rats. Ovaries are collected at 22:00 on the proestrus day and 10:00 on the following estrus day after a single dose of indomethacin and RU486. Histopathologically, changes depicting responses to LH surge were observed in ovaries, uteri and vagina. Total RNA was extracted from pre-ovulatory follicles or unruptured follicles collected by laser microdissection and analyzed by Genechip (R). Among genes showing statistically significant changes compared to control groups, following changes were considered relevant to induction of unruptured follicles. In indomethacin-treated rats, Wnt4 was down-regulated, suggesting effect on tissue integrity and steroid genesis. In RU486-treated rats, Adamts1, Adamts9, Edn2, Ednra, Lyve1, Plat, and Pparg were down-regulated. These changes suggest effects on proteolysis for extra cellular matrix or surrounding tissue (Adamts1 & 9, and Plat), constriction of smooth muscle surrounding follicles (Edn2, Ednra, and Pparg), follicular fluid (Lyve1), and angiogenesis (Pparg). Down-regulation of angiogenesis related genes (Angpt2, Hmox1, and Vegfa) was observed in both treatment groups. Here, we clarify genetic alterations induced by the inhibition of cyclooxygenase or progesterone receptor.
机译:众所周知,吲哚美辛(环氧合酶1和2抑制剂)和RU486(或米非司酮,孕酮受体拮抗剂)可阻断大鼠的卵泡破裂。为了表征未破裂卵泡中的遗传改变,在吲哚美辛和RU486处理的雌性Sprague-Dawley大鼠中分析了卵巢卵泡中的基因表达谱。单次服用消炎痛和RU486后,在发情日的22:00和第二个发情日的10:00收集卵巢。在组织病理学上,在卵巢,子宫和阴道中观察到了对LH激增的反应变化。从排卵前的卵泡或未破裂的卵泡中提取总RNA,并通过激光显微解剖收集并通过Genechip(R)分析。在与对照组相比显示出统计学上显着变化的基因中,以下变化被认为与诱导未破裂的卵泡有关。在消炎痛治疗的大鼠中,Wnt4被下调,表明对组织完整性和类固醇生成有影响。在RU486处理的大鼠中,Adamts1,Adamts9,Edn2,Ednra,Lyve1,Plat和Pparg下调。这些变化表明对细胞外基质或周围组织(Adamts1、9和Plat)的蛋白水解,卵泡周围的平滑肌(Edn2,Ednra和Pparg),卵泡液(Lyve1)和血管生成(Pparg)的影响。在两个治疗组中均观察到血管生成相关基因(Angpt2,Hmox1和Vegfa)的下调。在这里,我们阐明了由环氧合酶或孕激素受体的抑制所引起的遗传改变。

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