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

Abstract

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.

HMGB2 Promotes De Novo Lipogenesis to Accelerate Hepatocyte Proliferation During Liver Regeneration

“…3–5 Recently, we reported the pivotal role of HMGB2 in male and female reproductive tissues. 6–8 We also reported the crucial role of HMGB2 in the regulation of hepatocyte proliferation and cellular size during mouse liver regeneration. 9 However, the detailed molecular mechanisms of HMGB2 in regulating liver regeneration remain largely unknown.…”

“…Our other recent studies have also confirmed that HMGB2 is important for cell proliferation in mouse liver, testis, and ovary. [6][7][8] In recent studies, HMGB2 has been reported to be a novel adipogenic gene. The expression of HMGB2 induces adipogenesis in mesenchymal stem cells and fat infiltration into skeletal muscles through the HMG-B2-PDGFRα signaling cascade.…”

“…Our other recent studies have also confirmed that HMGB2 is important for cell proliferation in mouse liver, testis, and ovary. 6–8…”

“…Then, next primary antibody was reacted for overnight and repeated its detection with rhodamine-conjugated tyramide and then counterstained with 4′,6-diamidino-2-phenylindole (DAPI). 6,8 3, 3′-diaminobenzidine (DAB) visualization was used for FAT/CD36 and SREBP1 detection. As a negative control, normal mouse or rabbit IgG was used at the same concentration instead of the primary antibody in each experiment.…”

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

“…Following publication of the original article [ 1 ], the authors identified an error in authorgroup. Author name Fidya Fidya should be Fidya.…”