Low-dose aspirin can downregulate progesterone resistance and increase the expression of LIF in endometriosis during the implantation window

Abstract

Aim

Study the effect of low-dose aspirin on the endometrial receptivity in endometriosis rat models.

Materials and methods

This study is to explore the expressions of progesterone receptor and LIF among three groups of endometriosis rat models: control group (n = 12), EMs group (n = 15), and aspirin group (n = 17). The expressions of progesterone receptor (PR), PRA, PRB, and leukemia inhibitory factor receptor (LIFR) in eutopic endometrium were determined using immunohistochemistry technology, western blot, and qRT-PCR. The levels of LIF in eutopic endometrium and serum were detected by western blot, qRT-PCR, and ELISA.

Results

The expressions of PR, PRA, and PRB protein were significantly increased in the eutopic endometrium after low-dose aspirin treatment, and the level of PRB mRNA was also increased while the ratio of PRA/PRB mRNA was decreased in the eutopic endometrium. The levels of LIF in eutopic endometrium and serum were increased compared with the untreated endometriosis rats. However, the expression of LIFR was not statistically different among the three groups.

Conclusions

The results suggest that the low-dose aspirin treatment could downregulate progesterone resistance and increase the expression of LIF of endometriosis rats during the implantation window, which could improve endometrial receptivity and enhance the pregnant rate of endometriosis. It may provide a potential treatment method for endometriosis-related infertility.

低剂量阿司匹林可下调子宫内膜异位症患者种植窗口期的孕激素抵抗并增加LIF的表达 摘要

目的：研究低剂量阿司匹林对子宫内膜异位症大鼠模型子宫内膜容受性的影响。

材料与方法：本研究探讨了三组子宫内膜异位症大鼠模型中孕激素受体和LIF的表达：对照组（n＝12）, EMs组（n＝15）和阿司匹林组（n＝17）。通过免疫组织化学技术, western blot和qRT-PCR检测在位内膜的孕激素受体（PR）, PRA, PRB和白血病抑制因子受体（LIFR）的表达。通过Western blot、qRT-PCR和ELISA法检测在位内膜和血清中LIF的水平。

结果：低剂量阿司匹林治疗后, 在位内膜PR、PRA、PRB蛋白表达明显增加, PRB mRNA水平升高, PRA/PRB mRNA比值降低。子宫内膜异位症大鼠在位内膜和血清中LIF水平均高于未治疗组。而LIFR表达在三组间无统计学差异。

结论：结果表明, 低剂量阿司匹林治疗可下调子宫内膜异位症大鼠种植窗口期的孕激素抵抗, 增加LIF表达, 这可以提高子宫内膜容受性, 提高子宫内膜异位症的妊娠率。或许能为子宫内膜异位症相关的不孕提供潜在治疗方法。

Keywords:

• Low-dose aspirin
• endometriosis
• endometrial receptivity
• progesterone resistance
• LIF

Acknowledgments

The authors are grateful to all study participants, research fellows of Shandong Provincial Hospital Affiliated with Shandong University.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The study was supported by the grant NO. 2017YFC1001200 from the National Key Research and Development Program of China, the grant NO. 81671433 (MJL) from the National Natural Science Foundation of China and the grant NO. 201704072 from the Jinan City Science and Technology Development Plan.