Bone morphogenetic proteins and folliculogenesis: lessons from the Booroola mutation.
The Booroola phenotype is associated with a point mutation in the kinase domain of the bone morphogenetic protein receptor 1 B (BMPR1 B), and is characterized by 'precocious' differentiation of ovarian follicles, leading to the production of large numbers of ovulatory follicles that are smaller in diameter than wild-type follicles. These smaller follicles attain differentiation markers, such as expression of mRNA for P450 aromatase and inhibin-betaA subunit, granulosa cell LH receptors and aromatase activity, earlier than follicles from wild-type ewes. However, the preovulatory follicles from mutant ewes collectively secrete similar quantities of oestradiol, androstenedione and inhibin A in exactly the same pattern as wild-type ewes, which result in similar concentrations of FSH. The available evidence strongly indicates that the Booroola mutation exerts its action at the ovary rather than by altering gonadotrophin secretion. The bone morphogenetic protein (BMP) receptors and putative ligands are ubiquitously expressed within the ovary and BMPs seem to be involved in the paracrine regulation of FSH action. Thus, if the mutation is causing a reduction in BMPR1 B signalling, it may act on an inhibitor of follicle differentiation. Further research in this area will concentrate on the elucidation of the natural ligands for BMPR1 B at different stages of follicle development and examine the effect of BMPR1 B mutation on the downstream signalling cascade.
Souza
C J H
CJ
Department of Reproductive and Developmental Sciences, University of Edinburgh, Centre for Reproductive Biology, 49 Little France Crescent, Edinburgh EH16 4SB, UK. csouza@cenargen.embrapa.br
Campbell
B K
BK
McNeilly
A S
AS
Baird
D T
DT
D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D008098:Litter Size / Q000235:genetics; D006080:Ovarian Follicle / Q000502:physiology*; D010053:Ovary / Q000378:metabolism; D010060:Ovulation / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000235:genetics*; D012756:Sheep / Q000196:embryology / Q000235:genetics*
D019485:Bone Morphogenetic Proteins; D017978:Receptors, Growth Factor; D007987:Gonadotropin-Releasing Hormone; D005640:Follicle Stimulating Hormone; D017346:Protein Serine-Threonine Kinases; D052005:Bone Morphogenetic Protein Receptors, Type I