The novel peptide PFAP1 promotes primordial follicle activation by binding to MCM5. Issue 5 (22nd April 2023)

• Record Type: Journal Article
• Authors: Zhang, Yan; Wang, Hanbin; Zhu, Ye; Hou, Xiaojing; Li, Xing; Zhou, Xiaomei; Ge, Lili; Xu, Juan; Su, Yiping
• Is Part Of: FASEB journal. Volume 37:Issue 5(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-04-22
• Subjects: endogenous peptide -- granulosa cells -- MCM5 -- premature ovarian failure -- primordial follicle activation; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202201495RR
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: Premature ovarian failure (POF) is a complication of ovarian dysfunction resulting from the depletion or dysfunction of primordial follicles (PFs) in the ovaries. However, residual follicles that have the potential to be activated are present in POF or aged women. Little is known about the mechanisms by which the remaining dormant PFs in POF patients are activated. Using mass spectrometry, we screened differentially generated peptides extracted from the ovarian cortical tissue biopsies of patients with or without POF, during which we identified PFAP1, a peptide that significantly promoted the activation of PFs in the ovaries of 3 dpp mice in vitro. PFAP1 reversed age‐related fertility damage in vivo to a certain extent, promoted estrogen (E2) and anti‐mullerian hormone (AMH) production ( p < .05), and decreased the levels of follicle‐stimulating hormone (FSH) ( p < .05). In newborn mouse ovaries, PFAP1 could bind to the protein minichromosome maintenance protein 5 (MCM5) and inhibit its ubiquitination and degradation. In addition, PFAP1 promoted the proliferation of GCs, probably by regulating the function and production of MCM5. In conclusion, PFAP1 could promote the activation of PFs in the ovaries of newborn mice, partially restore the ovarian function of aged mice, and increase the proliferation of primary granulosa cells (GCs) by regulating the function of MCM5. PFAP1 is a promising novel peptide that may be developed into a new therapeutic agent for POF and other ovarian diseases. Abstract : A novel peptide PFAP1, which was highly enriched in ovarian cortical tissues from patients with normal ovary compared with that in POF patients, could promote primordial follicle activation in vitro and alleviate age‐related reproductive dysfunction in vivo. Mechanistically, the function of PFAF1 was at least partially mediated by binding and blocking ubiquitination of MCM5 in granulosa cells.