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. 2009 Dec;15(12):771-7.
doi: 10.1093/molehr/gap065. Epub 2009 Aug 25.

The Forkhead Transcription Factor FOXL2 Is Expressed in Somatic Cells of the Human Ovary Prior to Follicle Formation

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Free PMC article

The Forkhead Transcription Factor FOXL2 Is Expressed in Somatic Cells of the Human Ovary Prior to Follicle Formation

K Duffin et al. Mol Hum Reprod. .
Free PMC article

Abstract

Interactions between germ cells and surrounding somatic cells are central to ovarian development as well as later function. Disruption of these interactions arising from abnormalities in either cell type can lead to premature ovarian failure (POF). The forkhead transcription factor FOXL2 is a candidate POF factor, and mutations in the FOXL2 gene are associated with syndromic and non-syndromic ovarian failure. Foxl2-deficient mice display major defects in primordial follicle activation with consequent follicle loss, and earlier roles in gonadal development and sex determination have also been suggested. However, despite its importance no data presently exist on its expression in the developing human ovary. Expression of FOXL2 mRNA was demonstrated in the human fetal ovary between 8 and 19 weeks gestation, thus from soon after sex determination to primordial follicle development. Expression in the ovary was higher after 14 weeks than at earlier gestation weeks and was very low in the fetal testis at all ages examined. Immunolocalization revealed FOXL2 expression to be confined to somatic cells, both adjacent to germ cells and those located in the developing ovarian stroma. These cells are the site of action of oocyte-derived activin signalling, but in vitro treatment of human fetal ovaries with activin failed to reveal any regulation of FOXL2 transcription by this pathway. In summary, the expression of FOXL2 in somatic cells of the developing human ovary before and during follicle formation supports a conserved and continuing role for this factor in somatic/germ cell interactions from the earliest stages of human ovarian development.

Figures

Figure 1
Figure 1
Detection and quantification of FOXL2 gene expression in the human fetal gonad. (A) Expression of FOXL2 and GAPDH mRNA in the human fetal ovary and testis. Samples at indicated gestational age were analysed by RT–PCR. ‘+’ and ‘−’indicate the presence or absence of reverse transcriptase during cDNA synthesis. M: 100 bp ladder, bl: water blank in PCR reaction. (B) Quantitative PCR measurement of FOXL2 expression in the human fetal ovary at gestations of 8–9 weeks, 14–15 and 18–19 weeks as indicated, n = 4–5 per group. (C) Quantitative PCR measurement of Foxl2 expression in embryonic and post-natal mouse ovary at ages indicated, n = 3-5 per group. Both human and mouse data were analysed by ANOVA with Duncan's post hoc test using earliest gestation as comparator, *P < 0.05.
Figure 2
Figure 2
Immunolocalization of FOXL2 in the human fetal ovary. A and B, 14 weeks; C and D, 19 weeks. Positive immunofluorescence for FOXL2 is green, counterstain is propidium iodide (red), hence nuclear FOXL2 is yellow. Inset in (A) is negative control. (E, F) Double immunofluorescence for FOXL2 (green) and OCT4 (red) in human fetal ovary showing absence of colocalization, with FOXL2 expressed by somatic cells and OCT4 by germ cells. E, 9 weeks gestation; F, 19 weeks. Blue nuclear stain is DAPI. G: germ cell, S: somatic cell. Scale bars are 50 µm (A, applies to E and F) or 10 µm (B, C, D).
Figure 3
Figure 3
Expression of FOXL2 in disaggregated human fetal ovary (17–19 weeks gestation) cultured with activin A (10 ng/ml) for 4 or 24 h as indicated, or with follistatin (400 ng/ml, 24 h) versus untreated control cultures. Mean ± SEM, n = 5.

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