The different dosages of estrogen affect endometrial fibrosis and receptivity, but not SDF-1/CXCR4 axis in the treatment of intrauterine adhesions

Abstract

Objective: The study was to evaluate whether fibrotic markers, endometrial receptivity markers and SDF-1/CXCR4 had been changed in the treatment of intrauterine adhesions (IUAs) by different dosages of estrogen.

Study design: A total of 39 patients with IUAs were treated with EV 4 mg or 9 mg randomly post-surgery. TGF-β1/MMP-9, VEGF/αvβ3 and SDF-1/CXCR4 were detected in endometrial tissue before and after treatment by real-time PCR and Western blot.

Results: TGF-β1 and MMP-9 expression significantly decreased after treatment for 3 months than before (p < .05), the falling range was larger with EV 4 mg than 9 mg in the mild-moderate degree IUAs (p < .05); Integrin avβ3 expression significantly increased after treatment for 3 months than before (p < .05), the variation range was larger with EV 4 mg than 9 mg (p < .05); CXCR4 expression had no significant change after treatment 3 months compared to that before treatment (p > .05). SDF-1 presented an upward tendency at early phase, and it came back to the level of pre-surgery. But there were no significant difference between treatment with 4 mg and 9 mg in the rate of menstrual restoration and pregnancy follow-up 3 months after the treatment.

Conclusions: Endometrium fibrosis may be inhibited and endometrium receptivity may be improved by estrogen with moderate dosage therapy. Compared to the large one, it seems to be advantageous.

Chinese abstract

目的：评估不同剂量雌激素治疗宫腔粘连（IUAs）时纤维化标志物、子宫内膜容受性标志物与SDF-1/CXCR4是否改变。研究设计：共有39 IUAs患者术后随机使用4mg或9mg的戊酸雌二醇（EV）治疗。治疗前后通过实时PCR或蛋白质印迹检测内膜组织中TGF-β1/MMP-9, VEGF/avβ3 and SDF-1/CXCR4。结果：TGF-β1和MMP-9在治疗后3个月较治疗前明显下降（p<.05）, 在轻-中度IUAs患者中EV 4mg较9mg下降程度大（p<.05）；整合素avβ3在治疗后3个月较治疗前明显上升（p<.05）, EV 4mg较9mg变化幅度大（p<.05）；CXCR4在治疗前和治疗后3个月无明显变化（(p>.05）。SDF-1在早期呈上升趋势, 然后降回术前水平。但是4mg和9mg治疗在治疗3月后月经恢复和妊娠率无显著差异。讨论：适度雌激素治疗可能抑制子宫内膜纤维化, 提高子宫内膜容受性。与大剂量相比, 它似乎是有利的。

Keywords:

• CXCR4
• endometrial receptivity
• estradiol valerate
• fibrosis
• intrauterine adhesions

Disclosure statement

All authors declared that there is no conflict of interest.

Additional information

Funding

This research was supported by National Natural Science Foundation of China [grant no. 81471417].