The thrombospondin-1 receptor CD36 is an important mediator of ovarian angiogenesis and folliculogenesis

Abstract

BackgroundOvarian angiogenesis is a complex process that is regulated by a balance between pro- and anti-angiogenic factors. Physiological processes within the ovary, such as folliculogenesis, ovulation, and luteal formation are dependent upon adequate vascularization and anything that disrupts normal angiogenic processes may result in ovarian dysfunction, and possibly infertility. The objective of this study was to evaluate the role of the thrombospondin-1 (TSP-1) receptor CD36 in mediating ovarian angiogenesis and regulating ovarian function.MethodsThe role of CD36 was evaluated in granulosa cells in vitro and ovarian morphology and protein expression were determined in wild type and CD36 null mice.ResultsIn vitro, CD36 inhibition increased granulosa cell proliferation and decreased apoptosis. Granulosa cells in which CD36 was knocked down also exhibited an increase in expression of survival and angiogenic proteins. Ovaries from CD36 null mice were hypervascularized, with increased expression of pro-angiogenic vascular endothelial growth factor (VEGF) and its receptor VEGFR-2. Ovaries from CD36 null mice contained an increase in the numbers of pre-ovulatory follicles and decreased numbers of corpora lutea. CD36 null mice also had fewer number of offspring compared to wild type controls.ConclusionsThe results from this study demonstrate that CD36 is integral to the regulation of ovarian angiogenesis by TSP-1 and the expression of these family members may be useful in the control of ovarian vascular disorders.

Matricellular Proteins and Related ADAMTS Genes in Infertility

“…Overexpression of TSP-1 inhibits angiogenesis and consequently the folliculogenesis, driving the follicle to atresia. 47 Tenascin functions in ECM as an anti-adhesive, whereas fibronectin counteracts. Tenascin is expressed along with fibronectin in the tissues, in addition to whose its function requires, too, the presence of fibronectin.…”

The impact of tumor receptor heterogeneity on the response to anti-angiogenic cancer treatment

“…Thus, the fold-change of angiogenic ratio reflects how the anti-angiogenic therapy changes the amount of phosphorylated pro-angiogenic receptors relative to the activated anti-angiogenic receptors, which together mediate tumor angiogenesis. Multiple experimental studies qualitatively explore the activated (phosphorylated) levels of the angiogenic receptors in the context of the TSP1-VEGF axis; 47,[53][54][55][56] however, quantitative data needed to validate our model are still missing. Therefore, a direct comparison with the clinical measurements is not possible.…”

Role of pigment epithelium-derived factor in the reproductive system

“…TPS was found to be expressed in and secreted from granulosa cells regulated by gonadotropins. Knockout of TPS receptor has been correlated with increased ovarian vascularization and VEGF expression (Osz et al 2014). Hyaluronic acid, which is produced by cumulus cells, inhibits the activity of endothelial cells in vitro, an activity that is not hormonally regulated (Tempel et al 2000).…”

“…However, even after 70 years of research, the literature dealt more with the nature of the physiological pro-angiogenic factor of the ovary than with that of the anti-angiogenic one. Two anti-angiogenic candidates were suggested, thrombospondin (TPS; Osz et al 2014) and hyaluronic acid (Tempel et al 2000). TPS was found to be expressed in and secreted from granulosa cells regulated by gonadotropins.…”