The thrombospondin-1 receptor CD36 is an important mediator of ovarian angiogenesis and folliculogenesis
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RESEARCH
Open Access
The thrombospondin-1 receptor CD36 is an important mediator of ovarian angiogenesis and folliculogenesis Kata Osz, Michelle Ross and Jim Petrik*
Abstract Background: Ovarian 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. Methods: The 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. Results: In 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. Conclusions: The 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. Keywords: Ovary, CD36, Thrombospondin, Folliculogenesis, Angiogenesis
Background Ovarian folliculogenesis, ovulation, and formation of the corpus luteum require complex and coordinated interaction of numerous autocrine, paracrine, and endocrine factors to regulate important physiologic processes such as angiogenesis. Angiogenesis is the formation of new blood vessels from pre-existing vasculature. In the adult, angiogenesis is generally quiescent except for the vascularization required for wound healing. However, the female reproductive tract, including the ovaries, and uterus are unique as they are adult tissues that undergo cyclic angiogenic processes to facilitate processes important to reproduction. An important regulator of ovarian angiogenesis is vascular * Correspondence: [email protected] Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada
endothelial growth factor (VEGF), which stimulates endothelial proliferation, migration, and survival, and we have shown that through interaction with its receptor VEGFR2, it is an important survival factor for extravascular ovarian cells [1]. Thrombospondin-1 (TSP-1) is a large (450 kDa) multimodular glycoprotein encoded by the THSB1 gene that was originally identified as a major component of platelet α-granules [2,3]. Since then, TSP-1 has bee
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