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Therapeutic effect of human umbilical cord mesenchymal stem cells on tubal factor infertility using a chronic salpingitis murine model

  • Wenjuan Liao
  • Xinran Tang
  • Xiaomao LiEmail author
  • Tian Li
General Gynecology

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Human umbilical cord mesenchymal stem cells Tubal factor infertility Anti-inflammatory Anti-apoptotic 

Abbreviations

hUCMSCs

Human umbilical cord mesenchymal stem cells

MSCs

Mesenchymal stem cells

TFI

Tubal factor infertility

FT

Fallopian tube

IL-10

Interleukin-10

PCNA

Proliferating cell nuclear antigen

Caspase-3

Cysteine-containing aspartate-specific protease

Notes

Acknowledgements

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.

Author controbutions

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.

Funding

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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyThird Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina

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