Metformin reduces androgen receptor and upregulates homeobox A10 expression in uterine endometrium in women with polycystic ovary syndrome.
Metformin reduces androgen receptor and upregulates homeobox A10 expression in uterine endometrium in women with polycystic ovary syndrome.
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DOI：
10.1186/s12958-021-00765-6
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发表时间：
2021-05-31
期刊：
影响因子：
--
通讯作者：
Fujimori K
中科院分区：
文献类型：
--
作者：
Ohara M;Yoshida-Komiya H;Ono-Okutsu M;Yamaguchi-Ito A;Takahashi T;Fujimori K
多囊卵巢综合征（PCOS）导致无排卵，并与临床妊娠率降低有关。广泛用于治疗多囊卵巢综合征的二甲双胍可以通过恢复排卵周期和可能改善着床期子宫内膜异常而成功妊娠。然而，二甲双胍改善子宫内膜异常的机制尚不清楚。PCOS患者子宫内膜中类固醇激素受体和同源框A10（HOXA 10）表达异常，这对胚胎着床至关重要。在这项研究中，我们研究了二甲双胍是否影响雄激素受体（AR）和HOXA 10的表达在PCOS子宫内膜在体内和体外人子宫内膜细胞系。通过免疫组织化学、荧光免疫细胞化学和western blot分析评估AR和HOXA 10的表达。AR表达定位于上皮细胞和基质细胞;然而，HOXA 10表达仅限于本研究中的基质细胞。在患有PCOS的女性中，二甲双胍治疗后3个月，与治疗前的水平相比，上皮细胞和基质细胞中的AR表达减少。相比之下，二甲双胍处理的基质细胞中的HOXA 10表达与处理前的水平相比增加。此外，我们发现二甲双胍抵消了睾酮诱导的AR表达在石川细胞和人子宫内膜基质细胞（HESC）;而二甲双胍部分恢复了睾酮减少HOXA 10表达在HESC在体外。我们的研究结果表明，二甲双胍可能对PCOS患者雄激素过多的异常子宫内膜环境有直接影响。本研究获得了福岛医科大学伦理委员会的批准（批准编号504，批准日期。2006年7月6日），并获得所有患者的书面知情同意书。https://www.fmu.ac.jp/univ/sangaku/rinri.html
Polycystic ovary syndrome (PCOS) causes anovulation and is associated with a reduced clinical pregnancy rate. Metformin, which is widely used for treating PCOS, can lead to successful pregnancy by restoring the ovulation cycle and possibly improving endometrial abnormality during the implantation period. However, the mechanism by which metformin improves endometrial abnormality remains unknown. Women with PCOS have an aberrant expression of steroid hormone receptors and homeobox A10 (HOXA10), which is essential for embryo implantation in the endometrium. In this study, we examined whether metformin affects androgen receptor (AR) and HOXA10 expression in PCOS endometrium in vivo and in human endometrial cell lines in vitro. Expression of AR and HOXA10 was evaluated by immunohistochemistry, fluorescent immunocytochemistry, and western blot analysis. AR expression was localized in both epithelial and stromal cells; however, HOXA10 expression was limited to only stromal cells in this study. In women with PCOS, 3 months after metformin treatment, the expression of AR was reduced in epithelial and stromal cells in comparison to their levels before treatment. In contrast, HOXA10 expression in the stromal cells with metformin treatment increased in comparison to its level before treatment. Further, we showed that metformin counteracted the testosterone-induced AR expression in both Ishikawa cells and human endometrial stromal cells (HESCs); whereas, metformin partly restored the testosterone-reduced HOXA10 expression in HESCs in vitro. Our results suggest that metformin may have a direct effect on the abnormal endometrial environment of androgen excess in women with PCOS. The study was approved by the Ethical Committee of Fukushima Medical University (approval no. 504, approval date. July 6, 2006), and written informed consent was obtained from all patients. https://www.fmu.ac.jp/univ/sangaku/rinri.html
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影响因子：
11
作者：
Li X;Feng Y;Lin JF;Billig H;Shao R
通讯作者：
Shao R
影响因子：
9.2
作者：
Li X;Pishdari B;Cui P;Hu M;Yang HP;Guo YR;Jiang HY;Feng Y;Billig H;Shao R
通讯作者：
Shao R
DOI：
10.1056/nejmcp1514916
发表时间：
2016-07-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
McCartney CR;Marshall JC
通讯作者：
Marshall JC
对医疗统计信息的自由使用的易于使用的软件“ EZR”的调查。
影响因子：
4.8
作者：
Kanda Y
通讯作者：
Kanda Y
影响因子：
5.8
作者：
Cermik, D;Selam, B;Taylor, HS
通讯作者：
Taylor, HS