Gene expression analysis of human fetal ovarian primordial follicle formation.
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.
Fowler
Paul A
PA
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
Flannigan
Samantha
S
Mathers
Anna
A
Gillanders
Kim
K
Lea
Richard G
RG
Wood
Maureen J
MJ
Maheshwari
Abha
A
Bhattacharya
Siladitya
S
Collie-Duguid
Elaina S R
ES
Baker
Paul J
PJ
Monteiro
Ana
A
O'Shaughnessy
Peter J
PJ
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
D001324:Autoantigens; D051792:Basic Helix-Loop-Helix Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C539077:FIGLA protein, human; C527221:NLRP5 protein, human