Fxna, a novel gene differentially expressed in the rat ovary at the time of folliculogenesis, is required for normal ovarian histogenesis

Cecilia Garcia-Rudaz, Felix Luna, Veronica Tapia, Bredford Kerr, Lois Colgin, Francesco Galimi, Gregory A. Dissen, Neil D. Rawlings, Sergio R. Ojeda

    Research output: Contribution to journalArticle

    10 Scopus citations

    Abstract

    In rodents, the formation of ovarian follicles occurs after birth. In recent years, several factors required for follicular assembly and the growth of the newly formed follicles have been identified. We now describe a novel gene, Fxna, identified by differential display in the neonatal rat ovary. Fxna encodes an mRNA of 5.4 kb, and a protein of 898 amino acids. Fxna is a transmembrane metallopeptidase from family M28, localized to the endoplasmic reticulum. In the ovary, Fxna mRNA is expressed in granulosa cells; its abundance is maximal 48 hours after birth, i.e. during the initiation of follicular assembly. Reducing Fxna mRNA levels via lentiviral-mediated delivery of short hairpin RNAs to neonatal ovaries resulted in substantial loss of primordial, primary and secondary follicles, and structural disorganization of the ovary, with many abnormal follicles containing more than one oocyte and clusters of somatic cells not associated with any oocytes. These abnormalities were not attributable to either increased apoptosis or decreased proliferation of granulosa cells. The results indicate that Fxna is required for the organization of somatic cells and oocytes into discrete follicular structures. As an endoplasmic reticulum-bound peptidase, Fxna may facilitate follicular organization by processing precursor proteins required for intraovarian cell-to-cell communication.

    Original languageEnglish (US)
    Pages (from-to)945-957
    Number of pages13
    JournalDevelopment
    Volume134
    Issue number5
    DOIs
    StatePublished - Mar 1 2007

    Keywords

    • Follicular assembly
    • Follicular growth
    • Ovarian development
    • Peptidases
    • siRNAs

    ASJC Scopus subject areas

    • Molecular Biology
    • Developmental Biology

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