Follicle development can be divided into
gonadotrophin-independent, gonadotrophin-responsive
and gonadotrophin-dependent phases. The basic level of
control of folliculogenesis lies with the actions of an
extensively observed but poorly understood range of
somatic and germ cell derived local factors that
constitute an intrafollicular developmental cascade that
regulates the proliferative and differentiative phases of
follicle development. As follicle development
progresses, the follicle become increasingly responsive
to the actions of the pituitary gonadotrophins FSH and
LH and during these phases of development local
factors act to modulate the actions of gonadotrophins so
that the fate of each follicle depends on an intrafollicular
balance between local factors which augment
or attenuate gonadotrophic actions. Gonadotrophins are
therefore not a prerequisite for the continued growth of
gonadotrophin-responsive pre-antral follicles, but FSH
does appear to stimulate development and these actions
are modulated by local growth factors, such as IGFs,
AMH and BMPs. Naturally occurring mutations in
sheep for a number of these factors or there receptors
have provided insights into their roles during both the
early and terminal stages of follicle development and we
have recently produced extensive evidence supporting a
major role for members of the BMP system in
regulating follicle selection mechanisms through
increased activation of gonadotrophic augmentors
(BMP-6), decreased activation of attenuators (BMP-15,
GDF-9, AMH) or a combination of these two
mechanisms resulting in the deregulation of the normal
follicle selection mechanisms. The terminal stages of
follicle development, however, remain primarily under
the control of the pituitary gonadotrophins, with both
FSH and LH having essential and inter-related roles in
regulating final maturation and selection of the
ovulatory follicle and the oocyte which it contains.
