Cargando…

Effects of hPMSCs on granulosa cell apoptosis and AMH expression and their role in the restoration of ovary function in premature ovarian failure mice

BACKGROUND: This study was performed to determine the effects of human placenta mesenchymal stem cell (hPMSC) transplantation on granulosa cell apoptosis and anti-Müllerian hormone (AMH) and follicle-stimulating hormone receptor (FSHR) expression in autoimmune drug-induced premature ovarian failure...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Hongqin, Luo, Qianqian, Lu, Xueyan, Yin, Na, Zhou, Dongli, Zhang, Lianshuang, Zhao, Wei, Wang, Dong, Du, Pengchao, Hou, Yun, Zhang, Yan, Yuan, Wendan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793353/
https://www.ncbi.nlm.nih.gov/pubmed/29386068
http://dx.doi.org/10.1186/s13287-017-0745-5
_version_ 1783296932764975104
author Zhang, Hongqin
Luo, Qianqian
Lu, Xueyan
Yin, Na
Zhou, Dongli
Zhang, Lianshuang
Zhao, Wei
Wang, Dong
Du, Pengchao
Hou, Yun
Zhang, Yan
Yuan, Wendan
author_facet Zhang, Hongqin
Luo, Qianqian
Lu, Xueyan
Yin, Na
Zhou, Dongli
Zhang, Lianshuang
Zhao, Wei
Wang, Dong
Du, Pengchao
Hou, Yun
Zhang, Yan
Yuan, Wendan
author_sort Zhang, Hongqin
collection PubMed
description BACKGROUND: This study was performed to determine the effects of human placenta mesenchymal stem cell (hPMSC) transplantation on granulosa cell apoptosis and anti-Müllerian hormone (AMH) and follicle-stimulating hormone receptor (FSHR) expression in autoimmune drug-induced premature ovarian failure (POF) mice. The aim of this research is to investigate the mechanisms of hPMSCs on ovarian reserve capacity. METHODS: The POF mice model was established by injection of zona pellucida 3 peptide (pZP3). hPMSC transplantation was conducted by intravenous injection into mice following pZP3 treatment. The follicle number was examined by histopathology. The serum levels of FSH, LH, E(2), AMH and anti-zona pellucida antibody (AzpAb) were measured by enzyme-linked immunosorbent assay. AMH and FSHR expression in the ovary was analyzed by immunohistochemistry and western blot analysis. Granulosa cell apoptosis of the ovaries was examined by In Situ Cell Death Detection Kit. Granulosa cells were isolated and treated with SiAmh interference and hPMSC supernatant to observe the effects of AMH expression on granulosa cell apoptosis in vitro. RESULTS: The results showed that hPMSC transplantation can significantly recover the estrus cycle in the POF group. Morphological staining showed that the basal follicles and sinus follicles after hPMSC transplantation were higher in POF mice than in those without treatment, and the follicle number was significantly decreased with atresia. The serum levels of FSH, LH and AzpAb in the hPMSC transplantation group were reduced considerably, but the E(2) and AMH levels were significantly increased. After hPMSC transplantation, the AMH and FSHR expression in ovarian tissue was significantly higher than in the POF group as determined by immunochemistry and western blot analysis. The FSHR expression was shown in granulosa cells only, and FSHR expression increases with AMH expressed in the ovary; granulosa cell apoptosis was decreased following hPMSC transplantation. The same results were observed from the in-vitro study. CONCLUSIONS: hPMSC transplantation can significantly improve the serum levels of high gonadotropin and low estrogen of POF mice, promote follicular development, inhibit excessive follicular atresia and granulosa cell apoptosis, and improve the ovarian reserve capacity. The mechanism may be achieved by increasing the expression of AMH and FSHR in ovaries. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-017-0745-5) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-5793353
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-57933532018-02-12 Effects of hPMSCs on granulosa cell apoptosis and AMH expression and their role in the restoration of ovary function in premature ovarian failure mice Zhang, Hongqin Luo, Qianqian Lu, Xueyan Yin, Na Zhou, Dongli Zhang, Lianshuang Zhao, Wei Wang, Dong Du, Pengchao Hou, Yun Zhang, Yan Yuan, Wendan Stem Cell Res Ther Research BACKGROUND: This study was performed to determine the effects of human placenta mesenchymal stem cell (hPMSC) transplantation on granulosa cell apoptosis and anti-Müllerian hormone (AMH) and follicle-stimulating hormone receptor (FSHR) expression in autoimmune drug-induced premature ovarian failure (POF) mice. The aim of this research is to investigate the mechanisms of hPMSCs on ovarian reserve capacity. METHODS: The POF mice model was established by injection of zona pellucida 3 peptide (pZP3). hPMSC transplantation was conducted by intravenous injection into mice following pZP3 treatment. The follicle number was examined by histopathology. The serum levels of FSH, LH, E(2), AMH and anti-zona pellucida antibody (AzpAb) were measured by enzyme-linked immunosorbent assay. AMH and FSHR expression in the ovary was analyzed by immunohistochemistry and western blot analysis. Granulosa cell apoptosis of the ovaries was examined by In Situ Cell Death Detection Kit. Granulosa cells were isolated and treated with SiAmh interference and hPMSC supernatant to observe the effects of AMH expression on granulosa cell apoptosis in vitro. RESULTS: The results showed that hPMSC transplantation can significantly recover the estrus cycle in the POF group. Morphological staining showed that the basal follicles and sinus follicles after hPMSC transplantation were higher in POF mice than in those without treatment, and the follicle number was significantly decreased with atresia. The serum levels of FSH, LH and AzpAb in the hPMSC transplantation group were reduced considerably, but the E(2) and AMH levels were significantly increased. After hPMSC transplantation, the AMH and FSHR expression in ovarian tissue was significantly higher than in the POF group as determined by immunochemistry and western blot analysis. The FSHR expression was shown in granulosa cells only, and FSHR expression increases with AMH expressed in the ovary; granulosa cell apoptosis was decreased following hPMSC transplantation. The same results were observed from the in-vitro study. CONCLUSIONS: hPMSC transplantation can significantly improve the serum levels of high gonadotropin and low estrogen of POF mice, promote follicular development, inhibit excessive follicular atresia and granulosa cell apoptosis, and improve the ovarian reserve capacity. The mechanism may be achieved by increasing the expression of AMH and FSHR in ovaries. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-017-0745-5) contains supplementary material, which is available to authorized users. BioMed Central 2018-01-31 /pmc/articles/PMC5793353/ /pubmed/29386068 http://dx.doi.org/10.1186/s13287-017-0745-5 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zhang, Hongqin
Luo, Qianqian
Lu, Xueyan
Yin, Na
Zhou, Dongli
Zhang, Lianshuang
Zhao, Wei
Wang, Dong
Du, Pengchao
Hou, Yun
Zhang, Yan
Yuan, Wendan
Effects of hPMSCs on granulosa cell apoptosis and AMH expression and their role in the restoration of ovary function in premature ovarian failure mice
title Effects of hPMSCs on granulosa cell apoptosis and AMH expression and their role in the restoration of ovary function in premature ovarian failure mice
title_full Effects of hPMSCs on granulosa cell apoptosis and AMH expression and their role in the restoration of ovary function in premature ovarian failure mice
title_fullStr Effects of hPMSCs on granulosa cell apoptosis and AMH expression and their role in the restoration of ovary function in premature ovarian failure mice
title_full_unstemmed Effects of hPMSCs on granulosa cell apoptosis and AMH expression and their role in the restoration of ovary function in premature ovarian failure mice
title_short Effects of hPMSCs on granulosa cell apoptosis and AMH expression and their role in the restoration of ovary function in premature ovarian failure mice
title_sort effects of hpmscs on granulosa cell apoptosis and amh expression and their role in the restoration of ovary function in premature ovarian failure mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793353/
https://www.ncbi.nlm.nih.gov/pubmed/29386068
http://dx.doi.org/10.1186/s13287-017-0745-5
work_keys_str_mv AT zhanghongqin effectsofhpmscsongranulosacellapoptosisandamhexpressionandtheirroleintherestorationofovaryfunctioninprematureovarianfailuremice
AT luoqianqian effectsofhpmscsongranulosacellapoptosisandamhexpressionandtheirroleintherestorationofovaryfunctioninprematureovarianfailuremice
AT luxueyan effectsofhpmscsongranulosacellapoptosisandamhexpressionandtheirroleintherestorationofovaryfunctioninprematureovarianfailuremice
AT yinna effectsofhpmscsongranulosacellapoptosisandamhexpressionandtheirroleintherestorationofovaryfunctioninprematureovarianfailuremice
AT zhoudongli effectsofhpmscsongranulosacellapoptosisandamhexpressionandtheirroleintherestorationofovaryfunctioninprematureovarianfailuremice
AT zhanglianshuang effectsofhpmscsongranulosacellapoptosisandamhexpressionandtheirroleintherestorationofovaryfunctioninprematureovarianfailuremice
AT zhaowei effectsofhpmscsongranulosacellapoptosisandamhexpressionandtheirroleintherestorationofovaryfunctioninprematureovarianfailuremice
AT wangdong effectsofhpmscsongranulosacellapoptosisandamhexpressionandtheirroleintherestorationofovaryfunctioninprematureovarianfailuremice
AT dupengchao effectsofhpmscsongranulosacellapoptosisandamhexpressionandtheirroleintherestorationofovaryfunctioninprematureovarianfailuremice
AT houyun effectsofhpmscsongranulosacellapoptosisandamhexpressionandtheirroleintherestorationofovaryfunctioninprematureovarianfailuremice
AT zhangyan effectsofhpmscsongranulosacellapoptosisandamhexpressionandtheirroleintherestorationofovaryfunctioninprematureovarianfailuremice
AT yuanwendan effectsofhpmscsongranulosacellapoptosisandamhexpressionandtheirroleintherestorationofovaryfunctioninprematureovarianfailuremice