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Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility

BACKGROUND: High-Mobility Group Box 1 (HMGB1) and HMGB2 are chromatin-associated proteins that belong to the HMG protein family, and are involved in the regulation of DNA transcription during cell differentiation, proliferation and regeneration in various tissues. However, the role of HMGB2 in ovari...

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Autores principales: Shirouzu, Shinichiro, Sugita, Naohiro, Choijookhuu, Narantsog, Yamaguma, Yu, Takeguchi, Kanako, Ishizuka, Takumi, Tanaka, Mio, Fidya, Fidya, Kai, Kengo, Chosa, Etsuo, Yamashita, Yoshihiro, Koshimoto, Chihiro, Hishikawa, Yoshitaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9769043/
https://www.ncbi.nlm.nih.gov/pubmed/36539852
http://dx.doi.org/10.1186/s13048-022-01071-4
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author Shirouzu, Shinichiro
Sugita, Naohiro
Choijookhuu, Narantsog
Yamaguma, Yu
Takeguchi, Kanako
Ishizuka, Takumi
Tanaka, Mio
Fidya, Fidya
Kai, Kengo
Chosa, Etsuo
Yamashita, Yoshihiro
Koshimoto, Chihiro
Hishikawa, Yoshitaka
author_facet Shirouzu, Shinichiro
Sugita, Naohiro
Choijookhuu, Narantsog
Yamaguma, Yu
Takeguchi, Kanako
Ishizuka, Takumi
Tanaka, Mio
Fidya, Fidya
Kai, Kengo
Chosa, Etsuo
Yamashita, Yoshihiro
Koshimoto, Chihiro
Hishikawa, Yoshitaka
author_sort Shirouzu, Shinichiro
collection PubMed
description BACKGROUND: High-Mobility Group Box 1 (HMGB1) and HMGB2 are chromatin-associated proteins that belong to the HMG protein family, and are involved in the regulation of DNA transcription during cell differentiation, proliferation and regeneration in various tissues. However, the role of HMGB2 in ovarian folliculogenesis is largely unknown. METHODS: We investigated the functional role of HMGB1 and HMGB2 in ovarian folliculogenesis and fertilization using C57BL/6 wild type (WT) and HMGB2-knockout (KO) mice. Ovarian tissues were obtained from WT and HMGB2-KO mice at postnatal days 0, 3, 7, and 2, 6 months of age, then performed immunohistochemistry, qPCR and Western blotting analyses. Oocyte fertilization capability was examined by natural breeding and in vitro fertilization experiments. RESULTS: In HMGB2-KO mice, ovary weight was decreased due to reduced numbers of oocytes and follicles. Natural breeding and in vitro fertilization results indicated that HMGB2-KO mice are subfertile, but not sterile. Immunohistochemistry showed that oocytes expressed HMGB2, but not HMGB1, in neonatal and adult WT ovaries. Interestingly, in HMGB2-KO ovaries, a compensatory increase in HMGB1 was found in oocyte nuclei of neonatal and 2-month-old mice; however, this was lost at 6 months of age. CONCLUSIONS: The depletion of HMGB2 led to alterations in ovarian morphology and function, suggesting that HMGB2 plays an essential role in ovarian development, folliculogenesis and fertilization. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-022-01071-4.
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spelling pubmed-97690432022-12-22 Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility Shirouzu, Shinichiro Sugita, Naohiro Choijookhuu, Narantsog Yamaguma, Yu Takeguchi, Kanako Ishizuka, Takumi Tanaka, Mio Fidya, Fidya Kai, Kengo Chosa, Etsuo Yamashita, Yoshihiro Koshimoto, Chihiro Hishikawa, Yoshitaka J Ovarian Res Research BACKGROUND: High-Mobility Group Box 1 (HMGB1) and HMGB2 are chromatin-associated proteins that belong to the HMG protein family, and are involved in the regulation of DNA transcription during cell differentiation, proliferation and regeneration in various tissues. However, the role of HMGB2 in ovarian folliculogenesis is largely unknown. METHODS: We investigated the functional role of HMGB1 and HMGB2 in ovarian folliculogenesis and fertilization using C57BL/6 wild type (WT) and HMGB2-knockout (KO) mice. Ovarian tissues were obtained from WT and HMGB2-KO mice at postnatal days 0, 3, 7, and 2, 6 months of age, then performed immunohistochemistry, qPCR and Western blotting analyses. Oocyte fertilization capability was examined by natural breeding and in vitro fertilization experiments. RESULTS: In HMGB2-KO mice, ovary weight was decreased due to reduced numbers of oocytes and follicles. Natural breeding and in vitro fertilization results indicated that HMGB2-KO mice are subfertile, but not sterile. Immunohistochemistry showed that oocytes expressed HMGB2, but not HMGB1, in neonatal and adult WT ovaries. Interestingly, in HMGB2-KO ovaries, a compensatory increase in HMGB1 was found in oocyte nuclei of neonatal and 2-month-old mice; however, this was lost at 6 months of age. CONCLUSIONS: The depletion of HMGB2 led to alterations in ovarian morphology and function, suggesting that HMGB2 plays an essential role in ovarian development, folliculogenesis and fertilization. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13048-022-01071-4. BioMed Central 2022-12-20 /pmc/articles/PMC9769043/ /pubmed/36539852 http://dx.doi.org/10.1186/s13048-022-01071-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Shirouzu, Shinichiro
Sugita, Naohiro
Choijookhuu, Narantsog
Yamaguma, Yu
Takeguchi, Kanako
Ishizuka, Takumi
Tanaka, Mio
Fidya, Fidya
Kai, Kengo
Chosa, Etsuo
Yamashita, Yoshihiro
Koshimoto, Chihiro
Hishikawa, Yoshitaka
Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility
title Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility
title_full Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility
title_fullStr Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility
title_full_unstemmed Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility
title_short Pivotal role of High-Mobility Group Box 2 in ovarian folliculogenesis and fertility
title_sort pivotal role of high-mobility group box 2 in ovarian folliculogenesis and fertility
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9769043/
https://www.ncbi.nlm.nih.gov/pubmed/36539852
http://dx.doi.org/10.1186/s13048-022-01071-4
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