Transplantation induced pluripotent stem cells in situ improves fertility outcome impaired by intrauterine adhesions in mice

Intrauterine adhesion (IUA) is a common cause for secondary infertility. However, traditional treatment nowadays can only restore the shape of the uterine cavity but not the inadequate endometrium. In this study, we investigated the therapeutic potentials of induced pluripotent stem cells (iPSCs) to treat IUA in a mouse model and further explore the role of heme-oxygenase-1 (HO-1) gene in exerting such effects. Dual injury of lipopolysacchairdes and mechanical injury was first applied to establish an IUA model and different cells were then infused in situ into the mice uterus after modeling, including PBS, MEF, iPS, iPS-ho1siRNA and iPS-CT siRNA. Subsequent fertility outcomes were observed 28 d after treatment, so were the degree of tissue edema and inflammation 24 h and 5 d after treatment. Results showed that transplantation iPSCs in situ could significantly increase pregnancy rate and fetus number when compared with controls (PBS and MEF). Pathological studies also revealed that iPSCs could significantly ameliorated tissue edema and inflammation with the proof of having higher number of nucleus but less neutrophil than control groups 24 h after treatment. Furthermore, iPSCs were detected in the impaired endometrium by immunofluorescence staining 5 d after treatment. This, coupled with the increased level of ER expression and number of endometrial gland, strongly indicated the functional improvement of impaired endometrium. However, when knocking down HO-1 expression, the effect of iPSCs was significantly weakened. In conclusion, our results indicated that iPSCs might be a pragmatic solution for the treatment of IUA and HO-1 gene play an important role in regulating the therapeutic effect of iPSCs.