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Bmi1 Deficient Mice Exhibit Male Infertility
Previous studies have demonstrated that the polycomb repressor Bmi1 is universally expressed in all types of testicular cells and might regulate the spermatogonia proliferation, however, it is unclear whether Bmi1 plays a critical role in maintaining normal male fertility in vivo. To answer this que...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859480/ https://www.ncbi.nlm.nih.gov/pubmed/29559852 http://dx.doi.org/10.7150/ijbs.23325 |
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author | Dai, Xiuliang Zhang, Qian Yu, Zhenzhen Sun, Weiwei Wang, Rong Miao, Dengshun |
author_facet | Dai, Xiuliang Zhang, Qian Yu, Zhenzhen Sun, Weiwei Wang, Rong Miao, Dengshun |
author_sort | Dai, Xiuliang |
collection | PubMed |
description | Previous studies have demonstrated that the polycomb repressor Bmi1 is universally expressed in all types of testicular cells and might regulate the spermatogonia proliferation, however, it is unclear whether Bmi1 plays a critical role in maintaining normal male fertility in vivo. To answer this question, we first confirmed that Bmi1 is universally expressed in all types of testicular cells and found that the gene relative expression levels of Bmi1 in testis were the highest relative to other organs. Then we investigated the role of Bmi1 in maintaining normal male fertility using Bmi1 knockout male mouse model. Our results demonstrated that Bmi1 deficiency resulted in totally male infertility with smaller testis, severe oligospermia and sperm malformation. Mechanistically, decreased serum testosterone levels with down-regulating 3βHSD and 17βHSD expression levels, reduced germ cell proliferation, increased germ cell apoptosis with up-regulating p16, p19, p53 and p21 expression levels, increased reactive oxygen species (ROS) and H(2)O(2) levels with down-regulating gene expression levels of anti-oxidant enzymes, and increased 8-OHdG and γ.H2AX positive cells in testis were observed in Bmi1 deficient mice compared with wild-type mice. These results indicate that Bmi1 deficiency results in male infertility by reducing testosterone syntheses, increasing oxidative stress and DNA damage, activating p16 and p19 signaling pathway, inhibiting germ cell proliferation and inducing germ cell apoptosis and sperm malformation. Thus, Bmi1 may be a novel and potential target for the clinic treatment of male infertility. |
format | Online Article Text |
id | pubmed-5859480 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-58594802018-03-20 Bmi1 Deficient Mice Exhibit Male Infertility Dai, Xiuliang Zhang, Qian Yu, Zhenzhen Sun, Weiwei Wang, Rong Miao, Dengshun Int J Biol Sci Research Paper Previous studies have demonstrated that the polycomb repressor Bmi1 is universally expressed in all types of testicular cells and might regulate the spermatogonia proliferation, however, it is unclear whether Bmi1 plays a critical role in maintaining normal male fertility in vivo. To answer this question, we first confirmed that Bmi1 is universally expressed in all types of testicular cells and found that the gene relative expression levels of Bmi1 in testis were the highest relative to other organs. Then we investigated the role of Bmi1 in maintaining normal male fertility using Bmi1 knockout male mouse model. Our results demonstrated that Bmi1 deficiency resulted in totally male infertility with smaller testis, severe oligospermia and sperm malformation. Mechanistically, decreased serum testosterone levels with down-regulating 3βHSD and 17βHSD expression levels, reduced germ cell proliferation, increased germ cell apoptosis with up-regulating p16, p19, p53 and p21 expression levels, increased reactive oxygen species (ROS) and H(2)O(2) levels with down-regulating gene expression levels of anti-oxidant enzymes, and increased 8-OHdG and γ.H2AX positive cells in testis were observed in Bmi1 deficient mice compared with wild-type mice. These results indicate that Bmi1 deficiency results in male infertility by reducing testosterone syntheses, increasing oxidative stress and DNA damage, activating p16 and p19 signaling pathway, inhibiting germ cell proliferation and inducing germ cell apoptosis and sperm malformation. Thus, Bmi1 may be a novel and potential target for the clinic treatment of male infertility. Ivyspring International Publisher 2018-03-09 /pmc/articles/PMC5859480/ /pubmed/29559852 http://dx.doi.org/10.7150/ijbs.23325 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Dai, Xiuliang Zhang, Qian Yu, Zhenzhen Sun, Weiwei Wang, Rong Miao, Dengshun Bmi1 Deficient Mice Exhibit Male Infertility |
title | Bmi1 Deficient Mice Exhibit Male Infertility |
title_full | Bmi1 Deficient Mice Exhibit Male Infertility |
title_fullStr | Bmi1 Deficient Mice Exhibit Male Infertility |
title_full_unstemmed | Bmi1 Deficient Mice Exhibit Male Infertility |
title_short | Bmi1 Deficient Mice Exhibit Male Infertility |
title_sort | bmi1 deficient mice exhibit male infertility |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859480/ https://www.ncbi.nlm.nih.gov/pubmed/29559852 http://dx.doi.org/10.7150/ijbs.23325 |
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