Expression of PDGFs and Their Receptors in the Fetal and Adult Sheep Ovary.

Abstract

Platelet derived growth factors (PDGFs) and their receptors are key regulators of cell growth and angiogenesis, especially during fetal development. In rodents and humans, expression of PDGF mRNA was observed in specific ovarian compartments and the addition of PDGF to follicles in culture increased their size and enhanced the transition from primordial to primary follicles. Differences in the pattern of PDGF expression were noted depending on the species or age studied. However the effect of follicular health on expression has not been examined in depth. The objectives of this study were to determine the cell specific gene expression of PDGF ligands (PDGFA, B and C) and their receptors (PDGFRA and B) during ovarian and follicular development in sheep. Ovaries were collected from fetuses on days 55, 75 and 95 of gestation and from ewes at 4 weeks, 10 months, 2 years and 8 years of age and examined using in situ hybridization. During fetal life, PDGFA expression was sometimes associated with the vasculature and extra ovarian rete. Consistent expression was noted in the surface epithelium and in oocytes in both ovigerous cords and formed follicles. No expression was observed in granulosa cells of formed follicles or connecting rete. Fetal expression of PDGFB was similar to PDGFA at days 55 and 75; however no expression was apparent in the rete and by day 95 expression was largely confined to the surface epithelium. Expression of PDGFC was concentrated in the surface epithelium and cells surrounding the vasculature, with little or no expression observed in oocytes, follicles or in cells of the rete system. Postnatally, PDGFA and B were expressed in oocytes at all stages of follicular development from primordial to large antral follicles and in granulosa cells from the primary stage. Granulosa cell expression of PDGFC was evident in large preantral and small antral follicles. Thecal expression was not apparent until the large preantral stage and was initially restricted to PDGFB. At antral stages PDGFB was expressed predominantly in the theca interna while PDGFA was expressed in both theca interna and externa. PDGF receptors were not expressed in follicles until after antrum formation with PDGFRA expression in both theca interna and externa while PDGFRB expression was limited to theca interna. In general, atresia resulted in decreased expression of PDGFA and B in granulosa cells, increased expression of PDGFA and B in the thecal layers, increased expression of PDGFC in the granulosa and the appearance of PDGFC expression in the thecal layers. Only PDGFA expression was consistently noted in components of the ovarian rete system. Expression of PDGFA, B and C and PDGFRA and B was apparent throughout the CL, with receptor expression often associated with the vasculature. Cells associated with the vasculature showed expression of PDGFA, B and C, as well as PDGFA and B. Changes in expression patterns at different stages of follicular development along with changes associated with follicular atresia are consistent with a role for these factors in regulation of follicular development. (poster)