Abstract
BackgroundIntrauterine adhesion (IUA) is an adhesion of the uterine cavity or cervical canal resulting from damage to the basal layer of the endometrium; this condition is usually accompanied by fibrosis of the endometrium. Previous studies have demonstrated that human amniotic epithelial cells (hAECs) have stem cell characteristics; however, it is unclear whether hAECs have the therapeutic potential to restore fertility after IUA.MethodsA murine IUA model was established by mechanical injury to the uterus. Then, 106 hAECs were transplanted by intraperitoneal injection. The endometrium thickness, number of glands, and fibrosis area were measured by hematoxylin and eosin (H&E) staining and Masson staining. Molecules (including vWF, VEGF, PCNA, ER, PR, LC3, and p62) related to endometrial angiogenesis, cell proliferation, and autophagy were assayed by IHC staining. Pregnancy outcomes were also evaluated. Finally, hAECs were cocultured with human endometrial mesenchymal stem cells (hEnSCs) damaged by H2O2 to verify the paracrine effect on endometrial stromal cells in vitro.ResultsThe IUA uterine cavity presented with adhesion and even atresia, accompanied by a thinner endometrium, fewer glands, increased fibrosis area, and fewer microvessels. However, hAECs significantly improved the uterine structure after IUA. After hAEC treatment, the endometrium was thicker, the number of endometrial glands was increased, fibrosis was reduced, and more microvessels were generated. The expression levels of VEGF, PCNA, and ER were increased in the hAEC-treated endometrium, indicating improvements in angiogenesis and stromal cell proliferation. hAECs also increased pregnancy outcomes in IUA mice, and the pregnancy rate and fetus number increased. Furthermore, we observed altered autophagy in the IUA uterine model, and hAEC transplantation upregulated autophagy. An in vitro study showed that hAECs activated autophagy in (hEnSCs) treated with H2O2 in a paracrine manner.ConclusionsOur results demonstrated that hAECs have the potential to repair the uterus after injury, providing a new strategy for the prevention and treatment of Asherman syndrome.
Highlights
Intrauterine adhesion (IUA) is a consequence of endometrial trauma that leads to the complete or partial obstruction of the uterine cavity or cervical canal
The results showed that human amniotic epithelial cells (hAECs) expressed high levels of the stem cell marker SSEA4 and the epithelial marker CD324, while the expression of the mesenchymal marker CD146 and the immunogenicity indicator human leukocyte antigen HLA-DR was lacking (Fig. 1B)
Immunofluorescence assays further showed that the epithelial marker CK18 and the stem cell marker TRA-1-60 were both present in hAECs (Fig. 1C, D)
Summary
Intrauterine adhesion (IUA) is a consequence of endometrial trauma that leads to the complete or partial obstruction of the uterine cavity or cervical canal. Because two thirds of women with Asherman syndrome have undergone post-abortion/miscarriage curettage, it is necessary to take actions to prevent adhesion after invasive operations in the uterine cavity [6]. This can be accomplished via several methods, such as placing an intrauterine device (IUD)/Foley’s catheter balloon/hyaluronic acid in the uterine cavity or using conjugated estrogen treatment to facilitate endometrium recovery [7,8,9]. Intrauterine adhesion (IUA) is an adhesion of the uterine cavity or cervical canal resulting from damage to the basal layer of the endometrium; this condition is usually accompanied by fibrosis of the endometrium. HAECs were cocultured with human endometrial mesenchymal stem cells (hEnSCs) damaged by H2O2 to verify the paracrine effect on endometrial stromal cells in vitro
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