The novel peptide PFAP1 promotes primordial follicle activation by binding to MCM5

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.

The shared mechanism and potential diagnostic markers for premature ovarian failure and dry eye disease

“…Abnormalities in DNA replication are key to inducing reduced tearing and episodes of DED, which is consistent with the results of gene enrichment analysis. Primordial follicle depletion or dysfunction is key to the development of POF caused by MCM5, increasing the proliferation of primary granulosa cells, which, in turn, promotes the activation of primordial follicles in neonatal mouse ovaries 22 . The growth and development of mouse oocytes were found to be associated with three proteins of the MCM family: MCM2, MCM6, and MCM7 23 .…”