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

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 folliculo...

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Published in:Journal of ovarian research 2022-12, Vol.15 (1), p.133-133, Article 133
Main Authors: Shirouzu, Shinichiro, Sugita, Naohiro, Choijookhuu, Narantsog, Yamaguma, Yu, Takeguchi, Kanako, Ishizuka, Takumi, Tanaka, Mio, Fidya, Kai, Kengo, Chosa, Etsuo, Yamashita, Yoshihiro, Koshimoto, Chihiro, Hishikawa, Yoshitaka
Format: Article
Language:English
Subjects:
Analysis
Animals
Cell differentiation
Chromatin
Chromosomal proteins
Female
Fertility
folliculogenesis
Genetic transcription
HMGB1
HMGB2
HMGB2 Protein - genetics
HMGB2 Protein - metabolism
Immunohistochemistry
Mice
Mice, Inbred C57BL
Oocytes - metabolism
ovary
Ovary - metabolism
Transcription Factors - metabolism
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Summary: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. 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. 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. 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.
ISSN:1757-2215
1757-2215
DOI:10.1186/s13048-022-01071-4