title: Fxna, a novel gene differentially expressed in the rat ovary at the time of folliculogenesis, is required for normal ovarian histogenesis.
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.
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR , USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garcia-Rudaz
authors.forename: Felix
authors.initials: F
authors.lastname: Luna
authors.forename: Veronica
authors.initials: V
authors.lastname: Tapia
authors.forename: Bredford
authors.initials: B
authors.lastname: Kerr
authors.forename: Lois
authors.initials: L
authors.lastname: Colgin
authors.forename: Francesco
authors.initials: F
authors.lastname: Galimi
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Dissen
authors.forename: Neil D
authors.initials: ND
authors.lastname: Rawlings
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Ojeda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001483:Base Sequence; D049109:Cell Proliferation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D045726:Metalloproteases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D006080:Ovarian Follicle / Q000254:growth & development / Q000378:metabolism; D010053:Ovary / Q000254:growth & development* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid
chemical_list: C519596:Ermp1 protein, rat; D008565:Membrane Proteins; D012333:RNA, Messenger; D045726:Metalloproteases