Wu Di, Kimura Fuminori, Zheng Luyi, Ishida Mitsuaki, Niwa Yoko, Hirata Kimiko, Takebayashi Akie, Takashima Akiko, Takahashi Kentaro, Kushima Ryoji, Zhang Guangmei, Murakami Takashi
Department of Obstetrics and Gynecology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, 520-2192, Japan.
Department of Obstetrics and Gynecology, 1st Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang Province, 150001, China.
Reprod Biol Endocrinol. 2017 Mar 4;15(1):16. doi: 10.1186/s12958-017-0233-x.
Chronic endometritis (CE) is a continuous inflammation of uterine endometrium, and it is usually symptomless. As CE has been thought not to affect the reproductive status and general health of affected women, its significance has not been explored. However, recent studies have shown that CE is related with repeated implantation failures after in vitro fertilization-embryo transfer, unexplained infertility, and recurrent miscarriages. As decidua differentiates to support the implantation process and maintains the pregnancy, we hypothesized that CE may influence the process of decidualization.
Seventeen patients were employed in the experiment involving culture of endometrial stromal cells (ESCs). After obtaining endometrial samples, ESCs were harvested and cultured for 13 days. The concentrations in culture media and the protein expressions in ESCs of prolactin (PRL) and insulin-like growth factor binding protein-1 (IGFBP-1), two well known decidualization markers used in a large number of in vitro models, were analyzed by ELISA and Western blotting, respectively, and the cell numbers were also counted. The mRNA levels of PRL and IGFBP-1 were tested by quantitative real time polymerase chain reaction (RT-PCR). Since sex hormone induce proliferation and differentiation to decidua via binding to the sex hormone receptors (ERα, ERβ, PRA, and PRB), their expression was assessed in another 17 patients' paraffin-embedded endometrial tissue specimens by immunohistochemistry and semi-quantified by H-score.
Increased cell numbers and reduced secretion of PRL and IGFBP-1 were detected by ELISA in the ESCs of CE patients after culture for 13 days compared with non-CE patients. The decreased protein expression of IGFBP-1 in ESCs of CE patients was detected by Western blotting. The decreased expression of PRL mRNA and IGFBP-1 mRNA were detected by RT-PCR. Increased expressions of ERα, ERβ, PRA, and PRB were observed in the stromal cells of CE patients in comparison to non-CE patients, whereas increased expressions of ERα and ERβ were detected in the glandular cells of CE.
Our data suggests that CE modifies decidualization of human ESC through untuning the function of sex steroid hormone receptor.
慢性子宫内膜炎（CE）是子宫内膜的持续性炎症，通常无症状。由于一直认为CE不影响受影响女性的生殖状况和总体健康，其意义尚未得到探讨。然而，最近的研究表明，CE与体外受精-胚胎移植后反复着床失败、不明原因不孕和复发性流产有关。由于蜕膜分化以支持着床过程并维持妊娠，我们推测CE可能影响蜕膜化过程。
17名患者参与了涉及子宫内膜基质细胞（ESC）培养的实验。获取子宫内膜样本后，收获ESC并培养13天。分别通过酶联免疫吸附测定（ELISA）和蛋白质免疫印迹法分析培养基中的浓度以及催乳素（PRL）和胰岛素样生长因子结合蛋白-1（IGFBP-1）在ESC中的蛋白质表达，IGFBP-1是大量体外模型中使用的两种著名的蜕膜化标志物，同时还对细胞数量进行了计数。通过定量实时聚合酶链反应（RT-PCR）检测PRL和IGFBP-1的mRNA水平。由于性激素通过与性激素受体（ERα、ERβ、PRA和PRB）结合诱导向蜕膜的增殖和分化，通过免疫组织化学在另外17名患者的石蜡包埋子宫内膜组织标本中评估其表达，并通过H评分进行半定量。
与非CE患者相比，培养13天后，ELISA检测到CE患者的ESC中细胞数量增加，PRL和IGFBP-1的分泌减少。蛋白质免疫印迹法检测到CE患者的ESC中IGFBP-1的蛋白质表达降低。RT-PCR检测到PRL mRNA和IGFBP-1 mRNA的表达降低。与非CE患者相比，CE患者的基质细胞中ERα、ERβ、PRA和PRB的表达增加，而在CE的腺细胞中检测到ERα和ERβ的表达增加。
我们的数据表明，CE通过失调性甾体激素受体的功能来改变人ESC的蜕膜化。
