Development of the Rete Ovarii in the Sheep Ovary

Abstract

The rete ovarii is commonly described as a vestigial network of cells and tubules. While functions have been proposed for the rete during foetal ovarian development, its presence in the postnatal ovary is the subject of conflicting reports and no function has been attributed to the rete postnatally. The aim of this study was to assess the presence of the rete ovarii throughout foetal and adult life in the sheep ovary. An additional aim was to use structural information, cell proliferation data and gene expression data to review roles of the rete prenatally and propose roles postnatally.

Sheep ovaries were collected at days 55, 75 and 95 of gestation and at four weeks, seven months, two years and eight years of age postnatally. Serial sections were examined to determine structure, stereology performed to estimate rete volumes and BrdU immunohistochemistry performed to determine cell proliferations rates. In situ hybridisation was performed to determine expression of key genes involved in follicular development namely Follistatin (FST), Anti Mullerian Hormone (AMH), Aromatase (Cyp19A), Bone Morphogenetic Protein 4 (BMP4), Wilms Tumour (WT-1) as well as the Platelet Derived Growth Factors (PDGFA, PDGFB, PDGFC, PDGFD) and their receptors (PDGFRA, PDGFRB). Results show that cells of the rete arise from the regressing glomeruli and collecting ducts of the mesonephros. Mesangial cells appear to be the predominant cell of origin. Migration of the rete into the ovary occurs as a large membrane bound structure from day 55 to day 95 of gestation, at this time non membrane bound mesonephric derived cell streams are also apparent in the foetal ovary. Both CR and IR were present in all ovaries examined. While initially ER,, CR and IR are connected, the IR becomes isolated from the CR and ER during mid to late gestation. Differences in morphology, PAS staining patterns and gene expression also become apparent during this time period. Stereology showed that both IR and CR reached peak volumes at four weeks postnatally and declined thereafter. Labelling of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU) showed that peak proliferation rates of rete cells was achieved at day 95 of gestation. Significant levels of rete cell proliferation continued through until eight years of age. WT-1 gene was consistently expressed in rete cells and FST was expressed in the CR at most ages studied and at all ages in the IR. PDGFA and Cyp19A were expressed at foetal ages, while PDGFB and PDGFC were expressed in the IR at eight years of age. The results show that elements of the rete system have the potential to play roles in ovarian function through until at least eight years of age in the sheep. Functions ascribed to the rete during foetal ovarian development, notably in the initiation of meiosis may not be attributed to the rete but rather may be a function of the mesonephric derived cell streams. Cells of the rete may play a role in the development of the vasculature during foetal development through an oestrogen/PDGFA mechanism. Differences between the ER, CR and IR point to functional differences between rete components. There is no evidence to suggest that the rete plays a role in the initiation of follicle growth, however throughout both prenatal and postnatal life, cells of the rete appear to play a role in populating the ovarian cortex.