Department of Citology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.
Department of Citology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.
Toxicol Appl Pharmacol. 2018 Jan 15;339:73-84. doi: 10.1016/j.taap.2017.12.001. Epub 2017 Dec 5.
This study aimed to investigate the effects of soy isoflavones, genistein (GEN) and daidzein, (DAI) on the uterine function in ovary-intact middle-aged rats. GEN and DAI (35mg/kg) were subcutaneously administrated to acyclic (12-month-old) Wistar females, daily, for 4weeks. Control group received either vehicle (olive oil and ethanol, 9:1) or remained intact. We found that GEN and DAI differently affect uterine morphophysiology. GEN significantly increased the uterine wet weight which was associated with hyperplastic changes, revealed by stereological and histomorphometrical analyses. Also, PCNA immunoexpression was increased, whereas expression of apoptotic marker (caspase-3) was decreased. Protein and gene expressions of ERα were down-regulated, while PR and ERβ were up-regulated after GEN application. Also, GEN caused an increase of LAC and VEGF mRNA expression, together with an up-regulation of Akt activity. In contrast, DAI did not change the uterine wet weight and stereological features of the main uterine compartments as well as LAC and VEGF gene expression. Absence of hyperplastic changes were illustrated by an increase in caspase-3 immunoexpression, associated with reduced PCNA expression. DAI up-regulated only the expression of ERβ, while the expression levels of ERα and PR remain unaffected. Also, DAI inhibited the activation of Akt due to down-regulation of phosphorylated and total form of Akt protein expression. Compared to GEN, DAI did not promote events associated with the endometrial cell proliferation in the conducted study, figuring as the compound with a potential safety profile, which justifies further investigation.
本研究旨在探讨大豆异黄酮、染料木黄酮（GEN）和大豆苷元（DAI）对卵巢完整中年大鼠子宫功能的影响。将 GEN 和 DAI（35mg/kg）每天皮下注射给非周期性（12 个月大）Wistar 雌性大鼠，持续 4 周。对照组接受载体（橄榄油和乙醇，9:1）或保持完整。我们发现 GEN 和 DAI 对子宫形态生理学有不同的影响。GEN 显著增加了子宫湿重，这与立体学和组织形态计量学分析显示的增生变化有关。此外，PCNA 免疫表达增加，而凋亡标志物（半胱天冬酶-3）的表达减少。GEN 应用后，ERα 的蛋白和基因表达下调，而 PR 和 ERβ 表达上调。此外，GEN 导致 LAC 和 VEGF mRNA 表达增加，并上调 Akt 活性。相比之下，DAI 没有改变子宫湿重和主要子宫腔的立体学特征，以及 LAC 和 VEGF 基因表达。增生变化的缺失表现为 caspase-3 免疫表达增加，与 PCNA 表达减少相关。DAI 仅上调 ERβ 的表达，而 ERα 和 PR 的表达水平不受影响。此外，DAI 通过下调磷酸化和总形式的 Akt 蛋白表达抑制 Akt 的激活。与 GEN 相比，DAI 没有促进研究中与子宫内膜细胞增殖相关的事件，作为一种具有潜在安全特性的化合物，这证明了进一步的研究是合理的。
