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多囊卵巢综合征的分子调控:预处理和后处理小鼠模型中的基因表达水平改变。

Molecular regulation of polycystic ovary syndrome: altered gene expression levels in mouse models pretreatment and post-treatment.

机构信息

Near East University, Faculty of Medicine, Department of Medical Genetics, Nicosia, Cyprus.

Near East University, DESAM Research Institute, Nicosia, Cyprus.

出版信息

Zygote. 2022 Jun;30(3):352-357. doi: 10.1017/S0967199421000769. Epub 2021 Nov 3.

Abstract

Polycystic ovary syndrome (PCOS) is a complex disorder and genetic factors are believed to play a role. The main aim was to investigate expression levels of genes involved in PI3K/AKT signalling pathway pretreatment and post-treatment. Mouse models of PCOS were generated. Group one included control mice with no polycystic ovaries (n = 4), Group 2 included a PCOS mouse model (n = 8), Group 3 included PCOS mice treated with clomiphene citrate (n = 7) and Group 4 included PCOS mice treated with clomiphene citrate, metformin and pioglitazone (n = 8). Histochemical analyses were performed. Total RNA was extracted and cDNA was synthesized. Irs, Akt1 and Akt2, mTor and Pdpk1 gene expression levels were evaluated by RT-PCR amplification. In Group 1, cortex and medulla were evaluated as normal; in Group 2, ovarian cortex was composed of immature oocytes and cystic follicles with atretic follicles. In Groups 3 and 4, follicles were in the process of normal follicle differentiation. The expression levels of Akt1 and Pi3k were significantly different (P < 0.0001) between Groups 1 and 2. The significant differences in expression levels of Pi3k and Akt1 were also observed between the Group 1 and both Groups 3 and 4 (P < 0.0001). Furthermore, significant variations of the expression levels of mTor between Groups 1 and 4 were observed. The extrapolation of results of this study may imply that follicular development may be regulated by molecular pathways involving Pi3k, Akt1 and mTor expression. Therefore, genes in the PI3K/AKT pathway may have a direct regulatory role in the development of PCOS.

摘要

多囊卵巢综合征(PCOS)是一种复杂的疾病,遗传因素被认为起作用。主要目的是研究参与 PI3K/AKT 信号通路预处理和后处理的基因的表达水平。生成了 PCOS 的小鼠模型。第 1 组包括无多囊卵巢的对照小鼠(n = 4),第 2 组包括 PCOS 小鼠模型(n = 8),第 3 组包括用克罗米酚治疗的 PCOS 小鼠(n = 7),第 4 组包括用克罗米酚、二甲双胍和吡格列酮治疗的 PCOS 小鼠(n = 8)。进行了组织化学分析。提取总 RNA 并合成 cDNA。通过 RT-PCR 扩增评估 Irs、Akt1 和 Akt2、mTor 和 Pdpk1 基因的表达水平。在第 1 组中,皮质和髓质被评估为正常;在第 2 组中,卵巢皮质由未成熟卵母细胞和囊性卵泡以及闭锁卵泡组成。在第 3 组和第 4 组中,卵泡处于正常卵泡分化过程中。Akt1 和 Pi3k 的表达水平在第 1 组和第 2 组之间存在显著差异(P < 0.0001)。第 1 组与第 3 组和第 4 组之间也观察到 Pi3k 和 Akt1 表达水平的显著差异(P < 0.0001)。此外,还观察到第 1 组和第 4 组之间 mTor 表达水平的显著变化。本研究结果的推断可能意味着卵泡发育可能受到涉及 Pi3k、Akt1 和 mTor 表达的分子途径的调节。因此,PI3K/AKT 通路中的基因可能对 PCOS 的发展具有直接调节作用。

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