title: Development of steroid signaling pathways during primordial follicle formation in the human fetal ovary.
abstract: BACKGROUND
  Ovarian primordial follicle formation is critical for subsequent human female fertility. It is likely that steroid, and especially estrogen, signaling is required for this process, but details of the pathways involved are currently lacking.
  
  
  OBJECTIVE
  The aim was to identify and characterize key members of the steroid-signaling pathway expressed in the second trimester human fetal ovary.
  
  
  METHODS
  We conducted an observational study of the female fetus, quantifying and localizing steroid-signaling pathway members.
  
  
  METHODS
  The study was conducted at the Universities of Aberdeen, Edinburgh, and Glasgow.
  
  
  METHODS
  Ovaries were collected from 43 morphologically normal human female fetuses from women undergoing elective termination of second trimester pregnancies.
  
  
  METHODS
  We measured mRNA transcript levels and immunolocalized key steroidogenic enzymes and steroid receptors, including those encoded by ESR2, AR, and CYP19A1.
  
  
  RESULTS
  Levels of mRNA encoding the steroidogenic apparatus and steroid receptors increased across the second trimester. CYP19A1 transcript increased 4.7-fold during this period with intense immunostaining for CYP19A detected in pregranulosa cells around primordial follicles and somatic cells around oocyte nests. ESR2 was localized primarily to germ cells, but androgen receptor was exclusively expressed in somatic cells. CYP17A1 and HSD3B2 were also localized to oocytes, whereas CYP11A1 was detected in oocytes and some pregranulosa cells.
  
  
  CONCLUSIONS
  The human fetal ovary expresses the machinery to produce and detect multiple steroid signaling pathways, including estrogenic signaling, with the oocyte acting as a key component. This study provides a step-change in our understanding of local dynamics of steroid hormone signaling during the key period of human primordial follicle formation.
authors.affiliation: Centre for Reproductive Endocrinology and Medicine, Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom. p.a.fowler@abdn.ac.uk
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fowler
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
authors.forename: Philippa T
authors.initials: PT
authors.lastname: Saunders
authors.forename: Hazel
authors.initials: H
authors.lastname: Kinnell
authors.forename: J Ian
authors.initials: JI
authors.lastname: Mason
authors.forename: Dean B
authors.initials: DB
authors.lastname: Evans
authors.forename: Siladitya
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Samantha
authors.initials: S
authors.lastname: Flannigan
authors.forename: Stephen
authors.initials: S
authors.lastname: Franks
authors.forename: Ana
authors.initials: A
authors.lastname: Monteiro
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Shaughnessy
mesh_terms: D000704:Analysis of Variance; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D009865:Oocytes / Q000378:metabolism*; D010053:Ovary / Q000196:embryology / Q000378:metabolism*; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D011944:Receptors, Androgen; D001141:Aromatase