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

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.