sirtuins 在产后小鼠卵巢滤泡中的表达。

Expression of sirtuins in ovarian follicles of postnatal mice.

机构信息

Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Mol Reprod Dev. 2020 Oct;87(10):1097-1108. doi: 10.1002/mrd.23418. Epub 2020 Sep 9.

Abstract

Mammalian ovarian follicular development is an intricate, elaborate, and well-organized phenomenon regulated by various signaling pathways; however, the underlying mechanism remains unclear. Mammalian sirtuins (sirtuin 1 to sirtuin 7) are a group of NAD -dependent deacetylases implicated in various physiological processes including cell proliferation, apoptosis, cell cycle progression, and insulin signaling. Mammalian ovarian sirtuins have been studied using adult and aged bovine, porcine, and murine models. However, limited information is available regarding their precise expression patterns and the localization of follicle development in mice. This study aimed to assess the dynamic expression and localization of all seven sirtuins in early postnatal mouse ovaries through real-time polymerase chain reaction analysis and immunohistochemistry, respectively. During postnatal ovarian follicle development, sirtuin 1, sirtuin 4, and sirtuin 6 were downregulated compared with those in 1-day postnatal mouse ovaries (p < .05), indicating that these three sirtuin genes may be markers of follicular development. Combining their localization in granulosa cells through immunohistochemical studies, sirtuin 1, sirtuin 4, and sirtuin 6 are suggested to play negative regulatory roles in mammal ovarian follicular granulosa cell development. Furthermore, we found that sirtuin 2 (p < .05) and sirtuin 7 (p < .05) mRNA were constantly upregulated relative to sirtuin 1, although limited information is available regarding sirtuin 7. Among all sirtuins in mouse ovaries, sirtuin 1 was relatively and steadily downregulated. Upon sirtuin 1 overexpression in 1-day postnatal mouse ovaries via sirtuin 1-harboring adenoviruses in vitro, the emergence of primary follicles was delayed, as was the emergence of secondary follicles in 4-day postnatal ovaries. Further studies on KGN cell lines reported that interfering with sirtuin 1 expression in granulosa cell significantly affected granulosa cell proliferation and the expression of mitochondrial genes. This study presents the first systemic analysis of dynamic patterns of sirtuin family expression in early postnatal mice ovaries, laying the foundation for further studies on less discussed sirtuin subtypes, such as sirtuin 5 and sirtuin 7.

摘要

哺乳动物卵巢卵泡发育是一个复杂、精细和组织良好的现象,受多种信号通路调节;然而,其潜在机制尚不清楚。哺乳动物的 sirtuins(sirtuin 1 到 sirtuin 7)是一组 NAD 依赖性脱乙酰酶,参与多种生理过程,包括细胞增殖、凋亡、细胞周期进程和胰岛素信号转导。已经使用成年和老年牛、猪和鼠模型研究了哺乳动物的卵巢 sirtuins。然而,关于它们在小鼠中的精确表达模式和卵泡发育的定位,信息有限。本研究旨在通过实时聚合酶链反应分析和免疫组织化学分别评估 7 种 sirtuins 在新生后小鼠卵巢中的动态表达和定位。在产后卵巢卵泡发育过程中,与 1 日龄小鼠卵巢相比,sirtuin 1、sirtuin 4 和 sirtuin 6 的表达下调(p<.05),表明这 3 个 sirtuin 基因可能是卵泡发育的标志物。通过免疫组织化学研究将它们在颗粒细胞中的定位结合起来,sirtuin 1、sirtuin 4 和 sirtuin 6 被认为在哺乳动物卵巢卵泡颗粒细胞发育中发挥负调控作用。此外,我们发现 sirtuin 2(p<.05)和 sirtuin 7(p<.05)mRNA 的表达相对 sirtuin 1 持续上调,尽管关于 sirtuin 7 的信息有限。在小鼠卵巢的所有 sirtuins 中,sirtuin 1 相对稳定下调。通过在体外使用携带 sirtuin 1 的腺病毒过表达 1 日龄小鼠卵巢中的 sirtuin 1,初级卵泡的出现被延迟,4 日龄卵巢中的次级卵泡出现也被延迟。对 KGN 细胞系的进一步研究报告称,干扰颗粒细胞中 sirtuin 1 的表达显著影响颗粒细胞增殖和线粒体基因的表达。本研究首次对新生后小鼠卵巢中 sirtuin 家族表达的动态模式进行了系统分析,为进一步研究讨论较少的 sirtuin 亚型(如 sirtuin 5 和 sirtuin 7)奠定了基础。

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