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Abstract
An important but poorly understood process in ovarian
biology is the transition of the
developmentally arrested primordial follicle to the
developing primary follicle. Interactions
between the epithelial and mesenchymal cells of the
follicle are critical for the coordination of
ovarian follicle development. The mesenchymal growth
factor keratinocyte growth factor (KGF)
(i.e. fibroblast growth factor-7, FGF7) and the epithelial
growth factor Kit Ligand (KITL) are
known to interact to coordinate the growth of later stage
antral follicles. The hypothesis tested in
the current study is that KGF acts as a mesenchymal factor
to promote the primordial to primary
follicle transition. A postnatal 4-day-old rat ovary organ
culture system was used to investigate
the actions of KGF. KGF treatment promoted 65% of
follicles to undergo the primordial to
primary follicle transition, while only 45% undergo
development in control ovaries.
Neutralizing antibody for KGF was found to attenuate the
stimulatory action of KITL, but
neutralizing antibody for KITL was not able to attenuate
the stimulatory action of KGF. Further
analysis demonstrated that KGF was found to stimulate the
expression of KITL (i.e. mRNA
levels) by granulosa cells. KITL in turn was found to
stimulate the expression of KGF to create
a positive feedback loop. Interestingly, KGF expression
was localized to selected mesenchymal
cells (i.e. precursor theca cells) surrounding the
developing primordial follicle. Observations
suggest developing granulosa cells of the primordial
follicles produce KITL that helps recruit
precursor theca cells to the follicle that then produce
KGF that acts on the granulosa to amplify
KITL expression and support primordial follicle
development. KGF appears to be a
mesenchymal factor that promotes the primordial to primary
follicle transitions.
Key words:
Ovary
Follicle
Granulosa cells
Oocyte development
Theca cells
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