Therapeutic effect of human umbilical cord mesenchymal stem cells on tubal factor infertility using a chronic salpingitis murine model
The study was conducted to evaluate the application of human umbilical cord mesenchymal stem cells (hUCMSCs) in the treatment of tubal factor infertility (TFI) caused by Chlamydia trachomatis, and investigate their effect on fertility in animal models of chronic salpingitis.
In this study, we investigated the therapy effects of the transplantation of hUCMSCs in tubal factor infertility using a chronic salpingitis murine model which induced Chlamydia trachomatis. Twenty rats were divided into two groups: control group (n = 10) and treatment group (n = 10). hUCMSCs were given to mice after exposure to C. trachomatis for 4 weeks. After treatment for 4 weeks, five mice were randomly selected from each of the two groups to sacrifice and we examined the organ morphology and pathology, inflammatory cytokines, proliferation, and apoptosis in fallopian tube (FT).The remaining five mice from each group were caged 2:1 with male mice for another 4 weeks, the numbers of pregnant mice and the mean number of pups in the different groups were enumerated and calculated.
Intravaginal inoculation of hUCMSCs alleviated hydrosalpinx of the oviduct. EdU-labeled hUCMSCs are located at the interstitial site of the fallopian tube. Macrophage (F4/80) infiltration was significantly reduced in the treatment group compared with the control group and expression levels of the anti-inflammatory cytokine IL10 were increased after hUCMSCs treatment. Furthermore, mRNA and protein expression levels of PCNA and Caspase-3 were increased and decreased, respectively, in the hUCMSCs’ treatment group compared with the control. Moreover, hUCMSCs’ transplantation improved murine fertility.
Anti-inflammatory and anti-apoptotic effects of hUCMSCs may play an important role in TFI. Our data suggest that hUCMSCs’ transplantation contributed to the repair of tubal injury and improvement of fertility, providing a basis for assessing the contribution of stem cells in the oviduct for direct repair of the tube to assist reproduction.
KeywordsHuman umbilical cord mesenchymal stem cells Tubal factor infertility Anti-inflammatory Anti-apoptotic
Human umbilical cord mesenchymal stem cells
Mesenchymal stem cells
Tubal factor infertility
Proliferating cell nuclear antigen
Cysteine-containing aspartate-specific protease
The authors thank the Institute of Vaccines at the Third Affiliated Hospital of Sun Yat-sen University of the People's Republic of China for their help with study experimentation. We also thank all members in the department of Gynecology at the Third Affiliated Hospital of Sun Yat-sen University for their scientific advice and encouragement.
XM-L, TL, and XR-T conceived and designed the experiments. WJ-L, XM-L, TL, and XR-T performed the experiments. WJ-L and XR-T analyzed the data. WJ-L, XM-L, and TL contributed reagents/materials/analysis tools. WJ-L and XR-T wrote the paper. All authors read and approved the final manuscript. Ethics approval and consent to participate.This study was approved by the Ethics Committee of the the Third Affiliated Hospital of Sun Yat-sen University and run in accordance with the guidelines of the Helsinki Declaration. All participants provided written informed consent to participate in this study. All of the hUCMSCs in our study were manufactured and provided by the International Stem Cell Joint Research Center of Boyalife Stem Cell Technology Co., Ltd., Jiangsu province of China. All female and male C3H/HeN mice were were provided by the Beijing Vital-China Laboratory Animal Technology Co., Ltd.; (qualification no. SCXY (Beijing) 2016 - 0011). The Institute of Vaccines at the Third Affiliated Hospital of Sun Yat-sen University of the People's Republic of China approved the animal experimental protocol. Animals were used in accordance with the Animal Care and Use Committee of Sun Yat-sen University.
This study was supported by Wu Jieping Fund Medical Association (320.6755.15012) and Guangzhou Scientific Research Project (201607010085).
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
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