Osz Kata, Ross Michelle, Petrik Jim
Department of Biomedical Sciences, University of Guelph, Guelph, ON N1G 2W1, Canada.
Reprod Biol Endocrinol. 2014 Mar 14;12:21. doi: 10.1186/1477-7827-12-21.
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.
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.
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.
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.
卵巢血管生成是一个复杂的过程，受促血管生成因子和抗血管生成因子之间的平衡调节。卵巢内的生理过程，如卵泡发生、排卵和黄体形成，依赖于充足的血管化，任何破坏正常血管生成过程的因素都可能导致卵巢功能障碍，甚至可能导致不孕。本研究的目的是评估血小板反应蛋白-1（TSP-1）受体CD36在介导卵巢血管生成和调节卵巢功能中的作用。
在体外评估CD36在颗粒细胞中的作用，并在野生型和CD36基因敲除小鼠中测定卵巢形态和蛋白表达。
在体外，抑制CD36可增加颗粒细胞增殖并减少细胞凋亡。敲低CD36的颗粒细胞还表现出生存和血管生成蛋白表达增加。CD36基因敲除小鼠的卵巢血管化过度，促血管生成的血管内皮生长因子（VEGF）及其受体VEGFR-2的表达增加。CD36基因敲除小鼠的卵巢中排卵前卵泡数量增加，黄体数量减少。与野生型对照相比，CD36基因敲除小鼠的后代数量也较少。
本研究结果表明，CD36是TSP-1调节卵巢血管生成所必需的，这些家族成员的表达可能有助于控制卵巢血管疾病。
