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Gene Expression Analysis of Human Fetal Ovarian Primordial Follicle Formation

Divisions of Applied Medicine (Centre for Reproductive Endocrinology and Medicine) (P.A.F., S.F., A.M., K.G., E.S.R.C.-D.) and Applied Health Sciences (M.J.W., A.M., S.B.), Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom; School of Veterinary Medicine and Sciences (R.G.L.), University of Nottingham, Sutton Bonington LE15 5RD, United Kingdom; and Division of Cell Sciences (P.J.B., A.M., P.J.O.), University of Glasgow Veterinary School, Glasgow G61 1QH, United Kingdom

Address all correspondence and requests for reprints to: Prof. Paul A. Fowler, Ph.D., Centre for Reproductive Endocrinology and Medicine, Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, United Kingdom. E-mail: p.a.fowler{at}abdn.ac.uk.

Context: 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.

Design: We conducted an observational study of the female fetal gonad, comparing gene expression before and during primordial follicle formation.

Setting: The study was conducted at the Universities of Aberdeen, Glasgow, and Nottingham.

Patients/Participants: Ovaries were collected from 51 morphologically normal human female fetuses of women undergoing elective termination of normal second trimester pregnancies.

Main Outcome Measures: 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.

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