title: From primordial germ cells to primordial follicles: a review and visual representation of early ovarian development in mice.
abstract: BACKGROUND
  Normal development of reproductive organs is crucial for successful reproduction. In mice the early ovarian developmental process occurs during the embryonic and postnatal period and is regulated through a series of molecular signaling events. Early ovarian development in mice is a seventeen-day process that begins with the rise of six primordial germ cells on embryonic day five (E5) and ends with the formation of primordial follicles on postnatal day two (P2).
  
  
  RESULTS
  We reviewed the current literature and created a visual representation of early ovarian development that depicts the important molecular events and associated phenotypic outcomes based on primary data. The visual representation shows the timeline of key signaling interactions and regulation of protein expression in different cells involved in ovarian development. The major developmental events were divided into five phases: 1) origin of germ cells and maintenance of pluripotency; 2) primordial germ cell migration; 3) sex differentiation; 4) formation of germ cell nests; and 5) germ cell nest breakdown and primordial follicle formation.
  
  
  CONCLUSIONS
  This review and visual representation provide a summary of the current scientific understanding of the key regulation and signaling during ovarian development and highlights areas needing further study. The visual representation can be used as an educational resource to link molecular events with phenotypic outcomes; serves as a tool to generate new hypotheses and predictions of adverse reproductive outcomes due to perturbations at the molecular and cellular levels; and provides a comprehendible foundation for computational model development and hypothesis testing.
authors.affiliation: Institute of Environmental Health, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd. Mail code HRC3, Portland, OR, 97239, USA.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Wear
authors.affiliation: Institute of Environmental Health, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd. Mail code HRC3, Portland, OR, 97239, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: McPike
authors.affiliation: School of Public Health, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd. Mail code GH230, Portland, OR, 97239, USA. watanabk@ohsu.edu.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D002465:Cell Movement; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D038081:Organogenesis; D006080:Ovarian Follicle / Q000166:cytology* / Q000502:physiology*; D010053:Ovary / Q000196:embryology* / Q000502:physiology*; D012733:Sex Differentiation; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
keywords: Conceptual model; Early ovarian development; Molecular signaling; Mouse