title: Serine threonine kinase receptor associated protein regulates early follicle development in the mouse ovary.
abstract: The molecular mechanisms involved in regulating the development of small, gonadotrophin-independent follicles are poorly understood; however, many studies have highlighted an essential role for TGFB ligands. Canonical TGFB signalling is dependent upon intracellular SMAD proteins that regulate transcription. STRAP has been identified in other tissues as an inhibitor of the TGFB-SMAD signalling pathway. Therefore, in this study we aimed to determine the expression and role of STRAP in the context of early follicle development. Using qPCR, Strap, Smad3 and Smad7 revealed similar expression profiles in immature ovaries from mice aged 4-16 days containing different populations of early growing follicles. STRAP and SMAD2/3 proteins co-localised in granulosa cells of small follicles using immunofluorescence. Using an established culture model, neonatal mouse ovary fragments with a high density of small non-growing follicles were used to examine the effects of Strap knockdown using siRNA and STRAP protein inhibition by immuno-neutralisation. Both interventions caused a reduction in the proportion of small, non-growing follicles and an increase in the proportion and size of growing follicles in comparison to untreated controls, suggesting inhibition of STRAP facilitates follicle activation. Recombinant STRAP protein had no effect on small, non-growing follicles, but increased the mean oocyte size of growing follicles in the neonatal ovary model and also promoted the growth of isolated preantral follicles in vitro Overall findings indicate STRAP is expressed in the mouse ovary and is capable of regulating development of small follicles in a stage-dependent manner.
authors.affiliation: Academic Unit of Reproductive and Developmental MedicineDepartment of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: Isam B
authors.initials: IB
authors.lastname: Sharum
authors.affiliation: Academic Unit of Reproductive and Developmental MedicineDepartment of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: Sofia
authors.initials: S
authors.lastname: Granados-Aparici
authors.affiliation: Academic Unit of Reproductive and Developmental MedicineDepartment of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Warrander
authors.affiliation: Academic Unit of Reproductive and Developmental MedicineDepartment of Oncology and Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: Felicity P
authors.initials: FP
authors.lastname: Tournant
authors.affiliation: Academic Unit of Reproductive and Developmental MedicineDepartment of Oncology and Metabolism, University of Sheffield, Sheffield, UK m.a.fenwick@shefield.ac.uk.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Fenwick
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D005260:Female; D055785:Gene Knockdown Techniques; D006107:Granulosa Cells / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000187:drug effects / Q000254:growth & development; D006080:Ovarian Follicle / Q000254:growth & development*; D010053:Ovary / Q000254:growth & development* / Q000378:metabolism; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D051896:Smad Proteins, Receptor-Regulated / Q000235:genetics; D051899:Smad2 Protein / Q000032:analysis; D051900:Smad3 Protein / Q000032:analysis / Q000235:genetics; D059467:Transcriptome; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C116758:STRAP protein, mouse; D051896:Smad Proteins, Receptor-Regulated; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016212:Transforming Growth Factor beta