Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, 40530 Gothenburg, Sweden.
J Clin Endocrinol Metab. 2011 May;96(5):E869-77. doi: 10.1210/jc.2010-2353. Epub 2011 Feb 23.
Tissue-specific dicer1 knockout mice display severe, irreversible Fallopian tube damage and disrupted tubal transport. It is not known how Dicer1 affects human Fallopian tube function.
The aim of the study was to investigate the regulation of tubal Dicer1 expression during ovulation and the midsecretory phase and to assess Dicer1-associated alterations in estrogen receptor (ER) subtype and progesterone receptor (PR) expression.
Fallopian tissue was obtained from patients at early (n = 4), late (n = 4), and postovulatory (n = 5) phases and the midsecretory phase (n = 4). Serum was obtained immediately before surgery (sterilization or hysterectomy) to confirm the phases. The localization and regulation of Dicer1, ER subtypes, and PR isoforms were determined by immunofluorescence, confocal microscopy, and quantitative RT-PCR.
Dicer1 protein was expressed most abundantly in Fallopian epithelial cells; mRNA and protein levels peaked in the late ovulatory phase. ER subtype and PR isoform mRNA levels were not related to ovulatory stages; however, ERβ1 and ERβ2 mRNA/protein levels were highest and PRA/B and PRB mRNA/protein levels were lowest in the midsecretory phase. Dicer1 mRNA expression correlated positively with ERα mRNA expression in the late ovulatory phase and negatively with ERβ2 mRNA expression in the midsecretory phase and PRB mRNA in the early ovulatory phase.
Dicer1 expression is up-regulated in cell-specific fashion in human Fallopian tubes during ovulation. The stage-dependent expression of Dicer1 and its correlation with ERα, ERβ2, and PRB mRNA suggests that tubal Dicer1 helps regulate tubal expression of steroid hormone receptors in a cycle-dependent manner and may contribute to tubal transport in humans.
组织特异性的 dicer1 敲除小鼠表现出严重的、不可逆转的输卵管损伤和管腔运输中断。目前尚不清楚 Dicer1 如何影响人输卵管功能。
本研究旨在探讨排卵和中分泌期输卵管 Dicer1 表达的调节,并评估 Dicer1 相关的雌激素受体(ER)亚型和孕激素受体(PR)表达改变。
从早(n = 4)、晚(n = 4)和排卵后(n = 5)和中分泌期(n = 4)的患者中获取输卵管组织。在手术(绝育或子宫切除术)前立即获得血清以确认阶段。通过免疫荧光、共聚焦显微镜和定量 RT-PCR 确定 Dicer1、ER 亚型和 PR 同工型的定位和调节。
Dicer1 蛋白在输卵管上皮细胞中表达最丰富;mRNA 和蛋白水平在排卵后期达到峰值。ER 亚型和 PR 同工型 mRNA 水平与排卵阶段无关;然而,在中分泌期 ERβ1 和 ERβ2 mRNA/蛋白水平最高,PRB mRNA/蛋白水平最低。在排卵后期,Dicer1 mRNA 表达与 ERα mRNA 表达呈正相关,而在中分泌期与 ERβ2 mRNA 表达呈负相关,在早排卵期与 PRB mRNA 表达呈负相关。
在人类输卵管中,Dicer1 的表达在排卵时以细胞特异性方式上调。Dicer1 的阶段性表达及其与 ERα、ERβ2 和 PRB mRNA 的相关性表明,输卵管 Dicer1 以周期依赖性方式帮助调节类固醇激素受体在输卵管中的表达,并可能有助于人类的输卵管运输。