Endocrine Abstracts

BMPs form part of the TGFβ superfamily, which are important regulators of proliferation and differentiation in many cell types. The intraovarian production of specific BMP members and their receptors in a stage-specific manner is crucial for normal follicle development to proceed. Regulation of BMP signalling pathways can occur by intracellular inhibition of the signal transducers (Smads), or by BMP antagonists that bind extracellular BMPs to prevent or alter ligand–receptor interactions. Currently little is known about the spatio-temporal expression of BMP antagonists in the ovary or how they relate to early follicle development. We used the neonatal/juvenile mouse ovary model to examine mRNA expression of 19 candidate genes chosen based on their ability to interact with TGFβ superfamily members. All antagonists were amplified by RT-PCR in a range of adult mouse tissues and most (14) were detectable in young ovaries. Levels of each transcript were profiled in ovaries at 4, 8, 12 and 21 days of age by quantitative RT-PCR. On day 4 ovaries were enriched with mainly naked oocytes and primordial follicles, whereas days 8, 12 and 21 were characterised by the emergence of primary, secondary and larger preantral follicles respectively. Elevated gene expression was detectable on day 21 relative to earlier ages for connective tissue growth factor (Ctgf), follistatin (Fst), HtrA serine peptidase 1 (Htra1), noggin (Nog), gremlin 2 (Grem2) and twisted gastrulation homolog 1 (Twsg1) (P<0.05). Localisation of Fst, Htra1 and Grem2 by in situ hybridisation corroborated PCR results and revealed similar patterns of labelling with strong expression in granulosa cells of developing follicles. Intriguingly, Fst and Htra1 were expressed most strongly near the oocyte. The presence of multiple BMP antagonists in the young ovary implies the actions of certain growth factors may be neutralised and further highlights another important level of intraovarian regulation of follicle development.