Mechanisms Regulating Follicular Development and Selection of the Dominant Follicle

Reproductive function is an integrated process encompassing both extra-ovarian signals, such as gonadotrophins, and intrafollicular factors, such as locally produced growth factors. Initiation of primordial follicle growth and the early stages of folliculogenesis can occur without gonadotrophins. However, in vivo and in vitro studies indicate that FSH may stimulate the rate of preantral follicle growth and that it can take only 3 months for a primordial follicle to reach the ovulatory stage. Antral follicle development from 2 and 4 mm in diameter in sheep and cattle, respectively, is gonadotrophin dependent. During the oestrous cycle a transient increase in circulating FSH precedes the recruitment of a group of follicles. Recruited follicles are characterized by induction of expression of mRNAs encoding a range of steroidogenic enzymes, gonadotrophin receptors and local regulatory factors. As follicles continue to mature, there is a transfer of dependency from FSH to LH, which may be part of the mechanism involved in selection of follicles for continued growth. The mechanism of selection of the ovulatory follicle seems to be linked to the timing of mRNA expression encoding LHr and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in granulosa cells. Locally produced growth factors, such as the insulin-like growth factors (IGFs) and members of the transforming growth factor beta (TGFbeta) superfamily (inhibins, activins and bone morphogenetic proteins (BMPs)), work in concert with gonadotrophins throughout the follicular growth continuum. The roles of growth factors in follicular development and survival are dependent on gonadotrophin status and differentiation state, including morphology. In conclusion, it is the integration of extraovarian signals and intrafollicular factors that determine whether a follicle will continue to develop or be diverted into atretic pathways, as is the case for most of the follicles in monovulatory species, such as cattle.