Background
Tissue regeneration disorder after endometrial injury is an important cause of intrauterine adhesions, amenorrhea, and infertility in women. Both bone marrow mesenchymal stem cell (BMSC) transplantation and electroacupuncture (EA) are promising therapeutic applications for endometrial injury. This study examined their combined effects on thin endometrium in rats and the possible mechanisms underlying these effects.
Methods
A thin endometrial model was established in Sprague-Dawley (SD) rats by perfusing 95% ethanol into the right side of the uterus. The wounds were randomly treated with PBS (model group), BMSCs only (BMSC group), EA only (EA group), and BMSCs combined with EA (BMSC + EA group). Endometrial morphological alterations were observed by hematoxylin and eosin (H&E) staining. Changes in markers of epithelial and stromal endometrium cells, endometrial receptivity-related chemokines, and paracrine factors were detected using immunohistochemistry, western blotting, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Finally, the functional recovery of the uterus was evaluated by determining the rate of embryo implantation.
Results
As shown by endometrial morphology, the damaged uteri in all the treatment groups recovered to some extent, with the best effects observed in the BMSC + EA group. Further studies showed that EA promoted the migration of transplanted BMSCs to damaged uteri by activating the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 (SDF-1/CXCR4) axis. As compared with the other groups, upregulated expression of endometrial cytokeratin and vimentin, increased secretion of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in endometrial lesions, and improved embryo implantation rates on the 8th day of pregnancy were found in the BMSC + EA group.
Conclusions
EA plays an important role in supporting BMSCs in the repair of thin endometrium, most likely by promoting the migration of BMSCs and enhancing the paracrine effect of BMSCs.
Electronic supplementary material
The online version of this article (10.1186/s13287-019-1326-6) contains supplementary material, which is available to authorized users.
A thin endometrium affects the success of assisted reproduction due to low endometrial receptivity. Acupuncture improves endometrial receptivity and promotes the formation of pinopodes, the ultrastructure marker implantation window. However, the specific underlying mechanisms remain unclear. In this study, the efficacy of acupuncture treatment and its underlying mechanism were investigated by analyzing pregnancy rate, pinopode formation, and related molecular markers in thin endometrium model rats. Absolute ethanol (95%) was injected into the uteruses of female Sprague-Dawley rats to construct a thin endometrium model. In this model, acupuncture stimulation at EX-CA1, SP6, and CV4 ameliorated the pregnancy rate. Significantly increased embryo implantation, endometrial thickness, numbers of glands, and blood vessels were observed in the electroacupuncture (EA) group compared to the model group. The number of pinopodes in the EA group was abundant, with a shape similar to that of the control group. Additionally, significantly higher expression levels of pinopode-related markers, including integrin αvβ3, homeobox A10 (HOXA10), heparin-binding EGF-like growth factor (HBEGF), estrogen receptor alpha (ERα), and progesterone receptor (PR), were observed in the EA group than those in the model group. In conclusion, EA had a positive effect on the endometrial receptivity of thin endometrium model rats by improving pinopode formation through multiple molecular targets.
Objectives To conclude the evidence from systematic reviews (SRs) and meta-analyses assessing the effectiveness of acupuncture to treat couples with subfertility undergoing ART. Methods We searched the major databases from their inception to March 2018: PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chongqing VIP, and Sino-Med (the Chinese database). The primary outcomes of the overview were live birth and clinical pregnancy, and secondary outcomes were ongoing pregnancy, miscarriage, and adverse events. Study selection, quality assessment, and data extraction were performed independently by two review authors. Review methodological quality was assessed by using the AMSTAR tool, and the quality of the evidence was rated by GRADE methods. Results Eleven systematic reviews were included and published between 2009 and 2017. Our study showed that the acupuncture treatment seems to be a useful tool to improve the clinical pregnancy rate in patients who undergo assisted reproduction therapy. However, there was no evidence that acupuncture had any effect on live birth rate, ongoing pregnancy rates, or miscarriage regardless of whether acupuncture was performed around the time of oocyte retrieval or around the day of embryo transfer; this evidence is inconclusive because of the low quality of the included studies. Conclusions The evidence for acupuncture to treat couples with subfertility undergoing ART remains unclear. Further research is needed, with high-quality trials undertaken and reported.
Uterine adhesion (IUA), a leading cause of uterine infertility, is characterized by endometrial fibrosis. Implementing an appropriate animal model is essential for the research on the mechanisms of IUA. In the present study, we establish and evaluate different intrauterine adhesion modeling procedures in rats to provide a reference for researchers. Rat IUA models were established by mechanical injury, 95% ethanol injection, and dual (mechanical and infectious) injury. After two estrus cycles, the female rats were mated with sexually mature male rats and uterine tissues were obtained on the 5th day of pregnancy. HE staining and immunohistochemical detection of cytokeratin 19 and vimentin were performed to assess the morphology of the endometrium. The Masson staining and the expression of transforming growth factor -β1 and collagen Ι were used to assess the endometrium fibrosis. The expression of integrin avβ3, LIF, and HOXA10 in rat endometrium was used to evaluate the endometrial receptivity. In addition, the efficiency of embryo implantation was examined in the uterus on the 8th day of pregnancy. In conclusion, our study found that mechanical injury caused by the curette can be completely repaired after two estrus cycles. However, dual injury (mechanical injury with infection) and 95% ethanol injection can be used to establish the IUA rat model, and the dual damage is closer to the clinic-pathological characteristics of IUA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.