2. Academic Validation
  3. CCAAT/enhancer binding protein beta (C/EBPβ) regulates the formation of the ovarian reserve

CCAAT/enhancer binding protein beta (C/EBPβ) regulates the formation of the ovarian reserve

  • Commun Biol. 2025 Sep 30;8(1):1394. doi: 10.1038/s42003-025-08798-y.
Xiaoyuan Zhang # 1 2,  Yue Zeng # 1,  Zhanzhong Qiao 1,  Kexin Qin 1,  Pei Li 1,  Jiamao Yan 1 2,  Teng Zhang 2,  Yang Zhou 3,  Junjie Wang 4,  Wei Shen 5
Affiliations

Affiliations

  • 1 College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China.
  • 2 State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock (R2BGL), College of Life Sciences, Inner Mongolia University, Hohhot, China.
  • 3 State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock (R2BGL), College of Life Sciences, Inner Mongolia University, Hohhot, China. zhouyang106@126.com.
  • 4 College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China. 202101017@qau.edu.cn.
  • 5 College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, China. wshen@qau.edu.cn.
  • # Contributed equally.
PMID: 41028284 DOI: 10.1038/s42003-025-08798-y
Abstract

The primordial follicle (PF) pool (also known as ovarian reserve) is the only source of functional eggs during the reproductive lifespan, which formed at embryonic stage in most female mammals and is no longer renewed. CCAAT/enhancer binding protein beta (C/EBPβ) is a transcription factor (TF) and widely expressed in adult ovarian granulosa cells, but its role in the early ovarian development remains unclear. Here, we showed that C/EBPβ was enhanced during PF formation process in mice, and underwent nuclear translocation in germ cells along with the PF assembly (PFA) process. Importantly, the in vitro knockdown of C/EBPβ could inhibit the related proteins expression, resulting in the obstruction of PF formation. Mechanistically, the chromatin accessibility analysis revealed that C/EBPβ binds to the promoter region of the histone acetylase encoding gene Ep300 to promotes its expression, and enhance neurotrophic tyrosine receptor kinase (NTRK) signaling (required for PF formation) by maintaining chromatin accessibility of Furin promoter region. Interestingly, our results verified that the nuclear translocation of C/EBPβ is regulated by its phosphorylation level, and Lamin B1 acts as a "gatekeeper" molecule for the process. In summary, this report suggests that C/EBPβ is a key regulator for the establishment of ovarian reserve in mice.

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