title: Gene expression analysis of human fetal ovarian primordial follicle formation.
abstract: BACKGROUND
  Primordial follicle formation dictates the maximal potential female reproductive capacity and establishes the ovarian reserve. Currently, little is known about this process in the human.
  
  
  OBJECTIVE
  The aim of the study was to identify genes associated with the onset of human fetal primordial follicle formation in morphologically normal human fetuses.
  
  
  METHODS
  We conducted an observational study of the female fetal gonad, comparing gene expression before and during primordial follicle formation.
  
  
  METHODS
  The study was conducted at the Universities of Aberdeen, Glasgow, and Nottingham.
  
  
  METHODS
  Ovaries were collected from 51 morphologically normal human female fetuses of women undergoing elective termination of normal second trimester pregnancies.
  
  
  METHODS
  We performed fetal ovarian transcript expression by Affymetrix array and quantitative RT-PCR and gene product expression and localization by Western blot and immunohistochemistry.
  
  
  RESULTS
  Five transcripts were down-regulated and 61 were up-regulated in ovaries from older fetuses (18-20 wk) in which primordial follicle formation had started compared with younger (15-16 wk) fetuses in which no primordial follicles were observed. The altered genes contribute to major functions, including gene expression, tissue morphology, and apoptosis, that are essential for ovarian development. NALP5, the most highly regulated transcript, is an oocyte-specific maternal effect gene that is regulated downstream of FIGLA.
  
  
  CONCLUSIONS
  NALP5 probably plays a key role in the onset of human primordial follicle formation and thus the establishment of ovarian reserve in women.
authors.affiliation: Division of Applied Medicine, Centre for Reproductive Endocrinology and Medicine, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom. p.a.fowler@abdn.ac.uk
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fowler
authors.forename: Samantha
authors.initials: S
authors.lastname: Flannigan
authors.forename: Anna
authors.initials: A
authors.lastname: Mathers
authors.forename: Kim
authors.initials: K
authors.lastname: Gillanders
authors.forename: Richard G
authors.initials: RG
authors.lastname: Lea
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Wood
authors.forename: Abha
authors.initials: A
authors.lastname: Maheshwari
authors.forename: Siladitya
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Elaina S R
authors.initials: ES
authors.lastname: Collie-Duguid
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Baker
authors.forename: Ana
authors.initials: A
authors.lastname: Monteiro
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Shaughnessy
mesh_terms: D000028:Abortion, Induced; D001324:Autoantigens / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D009865:Oocytes / Q000502:physiology; D006080:Ovarian Follicle / Q000502:physiology*; D010053:Ovary / Q000502:physiology; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D014158:Transcription, Genetic
chemical_list: D001324:Autoantigens; D051792:Basic Helix-Loop-Helix Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C539077:FIGLA protein, human; C527221:NLRP5 protein, human