title: BCL2-modifying factor promotes germ cell loss during murine oogenesis.
abstract: Apoptosis plays a prominent role during ovarian development by eliminating large numbers of germ cells from the female germ line. However, the precise mechanisms and regulatory proteins involved in germ cell death are yet to be determined. In this study, we characterised the role of the pro-apoptotic BH3-only protein, BCL2-modifying factor (BMF), in germ cell apoptosis in embryonic and neonatal mouse ovaries. BMF protein was immunohistochemically localised to germ cells at embryonic days 15.5 (E15.5) and E17.5 and postnatal day 1 (PN1), coincident with entry into the meiotic prophase, but was undetectable at E13.5, and only present at low levels at PN3 and PN5. Consistent with this expression pattern, loss of BMF in female mice was associated with a decrease in apoptosis at E15.5 and E17.5. Furthermore, increased numbers of germ cells were found in ovaries from Bmf(-/-) mice compared with WT animals at E15.5 and PN1. However, germ cell numbers were comparable between Bmf(-/-) and WT ovaries at PN3, PN5 and PN10. Collectively, these data indicate that BMF mediates foetal oocyte loss and its action limits the maximal number of germ cells attained in the developing ovary, but does not influence the number of primordial follicles initially established in ovarian reserve.
authors.affiliation: Hudson Institute of Medical ResearchClayton, Victoria, Australia.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Vaithiyanathan
authors.affiliation: Development and Stem Cells ProgramMonash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Seng H
authors.initials: SH
authors.lastname: Liew
authors.affiliation: Development and Stem Cells ProgramMonash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
authors.forename: Nadeen
authors.initials: N
authors.lastname: Zerafa
authors.affiliation: Hudson Institute of Medical ResearchClayton, Victoria, Australia.
authors.forename: Thilini
authors.initials: T
authors.lastname: Gamage
authors.affiliation: The Walter and Eliza Hall Institute of Medical ResearchParkville, Victoria, Australia.
authors.forename: Michele
authors.initials: M
authors.lastname: Cook
authors.affiliation: The Walter and Eliza Hall Institute of Medical ResearchParkville, Victoria, Australia Department of Medical BiologyUniversity of Melbourne, Parkville, Victoria, Australia.
authors.forename: Lorraine A
authors.initials: LA
authors.lastname: O'Reilly
authors.affiliation: The Walter and Eliza Hall Institute of Medical ResearchParkville, Victoria, Australia Department of Medical BiologyUniversity of Melbourne, Parkville, Victoria, Australia.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouillet
authors.affiliation: The Walter and Eliza Hall Institute of Medical ResearchParkville, Victoria, Australia Department of Medical BiologyUniversity of Melbourne, Parkville, Victoria, Australia.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Scott
authors.affiliation: The Walter and Eliza Hall Institute of Medical ResearchParkville, Victoria, Australia Department of Medical BiologyUniversity of Melbourne, Parkville, Victoria, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
authors.affiliation: Hudson Institute of Medical ResearchClayton, Victoria, Australia Department of Obstetrics and GynaecologyMonash University, Clayton, Victoria, Australia.
authors.forename: Jock K
authors.initials: JK
authors.lastname: Findlay
authors.affiliation: Development and Stem Cells ProgramMonash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia Karla.Hutt@monash.edu.
authors.forename: Karla J
authors.initials: KJ
authors.lastname: Hutt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D005854:Germ Cells / Q000378:metabolism / Q000473:pathology*; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009865:Oocytes / Q000378:metabolism / Q000473:pathology*; D009866:Oogenesis / Q000502:physiology*; D010053:Ovary / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C435486:Bmf protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2