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[外阴子宫内膜异位症女性不孕症中子宫内膜容受性受损的形态学和分子生物学标志]

[The morphological and molecular biological signs of impaired endometrial receptivity in infertility in women suffering from external genital endometriosis].

作者信息

Paramonova N B, Kogan E A, Kolotovkina A V, Burmenskaya O V

机构信息

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia.

Lapino Clinical Hospital.

出版信息

Arkh Patol. 2018;80(3):11-18. doi: 10.17116/patol201880311-18.

Abstract

OBJECTIVE

To study endometrial receptivity in infertile women with external genital endometriosis (EGE).

SUBJECTS AND METHODS

Clinical, morphological, immunohistochemical, and molecular genetic examinations of endometrial aspiration pipelle biopsy specimens obtained on days 22-24 of the menstrual cycle from 94 infertile women with endometriosis: 50 women with Stage I-II EGE and 44 women with ovarian endometrioid cysts (OEC). A control group consisted of 54 women with tubal peritoneal factor of infertility (TPFI) and a successful attempt at IVF. Hematoxylin and eosin-stained sections were found to contain a number of endometrial surface epithelial cells containing mature pinopods. The expression levels of leukemia inhibitory factor (LIF), HOXA-10, glycodelin A, avβ3 integrin, estrogen receptors (ER) and progesterone receptors (PR), aromatase in the superficial epithelium, glandular epithelium and endometrial stroma were immunohistochemically revealed. Forty-four patients, including 17 with Stage I-II EGE and 27 with TPFI, showed mRNA expression levels of leukemia inhibitory factor receptor (LIFR), LIF, ER1, PgR, HOXA-10, and PTEN by real-time quantitative polymerase chain reaction (PCR) with a preliminary reverse transcription PCR assay.

RESULTS

It was established that in the infertile women with Stage I-II EGE and those with OEC, endometrial receptivity was impaired, which was manifested by a decline in the number of superficial epithelial cells containing mature pinopods, as well as a decrease in the endometrial level of the key receptivity markers: αvβ3 integrin, LIF, glycodelin A, and HOXA10 and increases in the synthesis of aromatase and in the imbalance of endometrial stromal expression of ER and PR detected by immunohistochemistry (IHC). Molecular genetic study showed lower mRNA expression levels of the HOXA-10, LIFR, and PgR genes, which confirms the data obtained by IHC.

摘要

目的

研究患有外阴子宫内膜异位症(EGE)的不孕女性的子宫内膜容受性。

对象与方法

对94例患有子宫内膜异位症的不孕女性在月经周期第22 - 24天获取的子宫内膜抽吸活检标本进行临床、形态学、免疫组织化学和分子遗传学检查,其中50例为Ⅰ - Ⅱ期EGE患者,44例为卵巢子宫内膜样囊肿(OEC)患者。对照组由54例因输卵管腹膜因素导致不孕(TPFI)且体外受精成功的女性组成。苏木精和伊红染色切片中发现许多含有成熟微绒毛的子宫内膜表面上皮细胞。通过免疫组织化学方法检测了白血病抑制因子(LIF)、HOXA - 10、糖蛋白A、αvβ3整合素、雌激素受体(ER)和孕激素受体(PR)、芳香化酶在表层上皮、腺上皮和子宫内膜基质中的表达水平。44例患者,包括17例Ⅰ - Ⅱ期EGE患者和27例TPFI患者,通过实时定量聚合酶链反应(PCR)及初步逆转录PCR检测白血病抑制因子受体(LIFR)、LIF、ER1、PgR、HOXA - 10和PTEN的mRNA表达水平。

结果

确定患有Ⅰ - Ⅱ期EGE的不孕女性和患有OEC的女性子宫内膜容受性受损,表现为含有成熟微绒毛的表层上皮细胞数量减少,以及关键容受性标志物的子宫内膜水平降低:αvβ3整合素、LIF、糖蛋白A和HOXA10,免疫组织化学(IHC)检测显示芳香化酶合成增加以及子宫内膜基质中ER和PR表达失衡。分子遗传学研究显示HOXA - 10、LIFR和PgR基因的mRNA表达水平较低,这证实了IHC获得的数据。

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