Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Apr 26, 2020; 12(4): 277-287
Published online Apr 26, 2020. doi: 10.4252/wjsc.v12.i4.277
Ability of human umbilical cord mesenchymal stem cells to repair chemotherapy-induced premature ovarian failure
Jian Shen, Dai Cao, Jing-Li Sun
Jian Shen, Dai Cao, Jing-Li Sun, Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command (Heping Campus), Shenyang 110000, Liaoning Province, China
Author contributions: All authors helped to perform the research; Shen J made the manuscript writing, performing procedures, data analysis and interpretation; Sun JL designed research; Cao D collected material and clinical data from patients.
Institutional animal care and use committee statement: The study was reviewed and approved by the Institutional Animal Care and Use Committee at General Hospital of Northern Theater Command.
Conflict-of-interest statement: No conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Jing-Li Sun, MAMS, Chief Physician, Department of Obstetrics and Gynecology, General Hospital of Northern Theater Command (Heping Campus), No. 5 Guangrong Street, Heping District, Shenyang 110000, Liaoning Province, China. zg3416@sina.com
Received: December 1, 2019
Peer-review started: December 1, 2019
First decision: January 13, 2020
Revised: March 19, 2020
Accepted: March 26, 2020
Article in press: March 26, 2020
Published online: April 26, 2020
Processing time: 147 Days and 10.9 Hours
Abstract
BACKGROUND

Premature ovarian insufficiency (POI) and premature ovarian failure (POF) have become one of the major problems threatening women of childbearing age. Studies have shown that stem cells transplanted from bone marrow, umbilical cord, peripheral blood and amniotic fluid can migrate and proliferate to the ovary, promote ovarian function repair, increase the number of follicles and granulosa cells at all levels of ovary, improve endocrine function, and can differentiate into oocytes in specific ovarian environment to restore fertility to some extent.

AIM

To study the ability of human umbilical cord mesenchymal stem cells (hUCMSCs) to repair ovarian injury after chemotherapy.

METHODS

A total of 110 female BALB/c mice (aged 7-8 wk old) with body masses of 16.0-20.0 g were selected. The mice were fed until 12 wk of age, and cyclophosphamide was administered by intraperitoneal injection for 14 consecutive days to induce premature ovarian failure in mice. Seventy-five mice with estrous cycle disorder were screened and randomly divided into 3 groups according to their body weight: model group, positive control group and hUCMSC group, and each group had 25 mice. Another 25 mice were used as negative controls. The mice in the hUCMSC group were injected with hUCMSCs in the tail vein, and the mice in the positive control group were given an oestradiol valerate solution and a medroxyprogesterone acetate solution in the tail vein. On the 1st, 15th, 30th, 45th, and 60th days after intravenous administration, vaginal smears were made to monitor the estrous cycles of the mice. The ovaries were weighed, and pathological sections were made to observe the morphology of the follicles; blood samples were collected to monitor the concentration of sex hormones (oestradiol and follicle-stimulating hormone).

RESULTS

The estrous cycles of the model group mice were disrupted throughout the experiment. Mice in the hUCMSC group and the positive control group resumed normal estrous cycles. The ovarian weight of the model group mice continued to decline. The ovarian weight of the hUCMSC group mice and the positive control group mice decreased first and then gradually increased, and the ovarian weight of the hUCMSC group mice was heavier than that of the positive control group mice. The difference was statistically significant (P < 0.05). Compared with the negative control group, the model group experienced a decrease in oestradiol and an increase in follicle-stimulating hormone, and the difference was statistically significant (P < 0.05). Compared with the model group, the hUCMSC and positive control groups experienced a slight increase in oestradiol and a decrease in follicle-stimulating hormone; the difference was statistically significant (P < 0.05). The pathological examination revealed that the mouse ovaries from the model group were atrophied, the volume was reduced, the cortical and medullary structures were disordered, the number of follicles at all stages was significantly reduced, the number of atretic follicles increased, the number of primordial follicles and corpus luteum significantly decreased, and the corpus luteum had an irregular shape. Compared with those of the model group, the lesions of the hUCMSC and positive control groups significantly improved.

CONCLUSION

hUCMSCs can repair ovarian tissue damaged by chemotherapy to a certain extent, can improve the degree of apoptosis in ovarian tissue, and can improve the endocrine function of mouse ovaries.

Keywords: Umbilical cord mesenchymal stem cells; Premature ovarian failure; Chemotherapy; Repair; Ovarian injury; Endocrine function

Core tip: Human umbilical cord mesenchymal stem cells (hUCMSCs) can repair ovarian tissue damaged by chemotherapy to a certain extent, can improve the degree of apoptosis in ovarian tissue, and can improve the endocrine function of mouse ovaries. The effect of hUCMSCs on chemotherapy-induced premature ovarian failure mice was observed by closely monitoring the changes in mouse ovarian structure and endocrine function to further verify whether hUCMSCs can be used in the treatment of chemotherapy-induced premature ovarian failure.