ABSTRACT
Cystic ovarian disease (COD) is one of the main causes of infertility in dairy cattle. It has been shown that intra-ovarian factors, such as members of the insulin-like growth factor (IGF) system, may contribute to follicular persistence. The bioavailability of IGF to initiate its response by binding to specific receptors (IGFRs) depends on interactions with related compounds, such as pregnancy-associated plasma protein A (PAPP-A). The aim of this study was to determine IGFR1 and PAPP-A expression both in follicles at different stages of development and in cysts, to evaluate the roles in the etiopathogenesis of COD in cattle. The mRNA expression of PAPP-A was higher in granulosa cells of large tertiary follicles than in cysts, whereas the protein PAPP-A present in the follicular fluid from these follicles showed no differences. Although no PAPP-A mRNA expression was detected in smaller tertiary follicles, in their follicular fluid, this protease was detected in lesser concentration than in cysts. The mRNA expression of IGFR1 was lower in granulosa cells from cystic follicles than in those from tertiary ones. However, the protein expression of this receptor presented the highest levels in cystic structures, probably to increase the possibility of IGF response. The data obtained would indicate that animals with COD have an altered regulation of the IGF system in the ovary, which could be involved in the pathogenesis of this disease in cattle.
Subject(s)
Cattle Diseases/physiopathology , Ovarian Cysts/veterinary , Pregnancy-Associated Plasma Protein-A/physiology , Receptor, IGF Type 1/physiology , Animals , Cattle , Cattle Diseases/etiology , Female , Follicular Fluid/chemistry , Gene Expression , Granulosa Cells/chemistry , Immunohistochemistry , Ovarian Cysts/chemistry , Ovarian Cysts/physiopathology , Ovarian Follicle/chemistry , Pregnancy , Pregnancy-Associated Plasma Protein-A/analysis , Pregnancy-Associated Plasma Protein-A/genetics , RNA, Messenger/analysis , Receptor, IGF Type 1/analysis , Receptor, IGF Type 1/geneticsABSTRACT
Cystic ovarian disease (COD) is one of the main factors responsible for reproductive disorders in cattle. Although the pathogenesis and mechanism of cyst formation are not fully understood, it has been proposed that the IGF system could play an essential role, as it is a key intraovarian regulator. The aim of the present study was to determine whether the altered levels in IGF1 detected in bovines with COD are associated with changes at mRNA level or with differential modulation by IGFBPs. The mRNA levels of the IGF components studied were analyzed by real time PCR and in situ hybridization, and IGFBP expression and activity were assayed by immunohistochemistry and ligand blot, respectively. Results showed a decreased IGF1 mRNA level due to a lower granulosa cell gene expression in cystic follicles (P<0.05). Results also showed variations in IGFBP expression in the intraovarian cellular compartment and concentration in follicular fluid, and suggest that IGFBP3 is a key regulator of intrafollicular IGF1 in animals with COD.
