Robinson R S, Nicklin L T, Hammond A J, Schams D, Hunter M G, Mann G E
Division of Animal Physiology, University of Nottingham, Loughborough, LEICS LE12 5RD, United Kingdom.
Biol Reprod. 2007 Jul;77(1):28-36. doi: 10.1095/biolreprod.106.055434. Epub 2007 Mar 14.
Luteal inadequacy is a major cause of infertility in a number of species. During the early luteal phase, progesterone production requires the rapid growth of the corpus luteum (CL), which is in turn dependent on angiogenesis. In the present study, we examined the temporal changes in vascular endothelial growth factor A (VEGFA), fibroblast growth factor 2 (FGF2) and secreted protein, acidic, cysteine-rich (osteonectin) (SPARC) during the follicular-luteal transition and CL development in the cow. Luteal VEGFA concentrations increased as the CL developed but were lower in the regressing CL. Conversely, luteal FGF2 concentrations were highest immediately postovulation in the collapsed follicle and declined as the CL developed. Furthermore, three FGF2 isoforms were present in the collapsed follicle, but only one isoform was detected in older CL. Interestingly, FGF2 concentrations increased in the regressing CL. Western blot analysis for SPARC showed the presence of two isoforms, which were constitutively expressed throughout CL development. Further studies investigated the regulation of FGF2 by LH, which showed that FGF2 concentrations in preovulatory follicular fluid were higher in those animals that had experienced an LH surge. Moreover, LH stimulated FGF2 production in dispersed luteal cells. Conversely, the LH surge had no effect on follicular fluid VEGFA concentrations. In conclusion, FGF2 was more dynamic than VEGFA and SPARC during the follicular-luteal transition, which suggests that FGF2 plays a key role in the initiation of angiogenesis at this time. Furthermore, it is likely that this is stimulated by the LH surge. The results also suggest that VEGFA and SPARC have a more constitutive, but essential, role in the development of the CL vasculature.
黄体功能不全是许多物种不孕的主要原因。在黄体早期,孕酮的产生需要黄体(CL)的快速生长,而这又依赖于血管生成。在本研究中,我们检测了牛卵泡 - 黄体转变和CL发育过程中血管内皮生长因子A(VEGFA)、成纤维细胞生长因子2(FGF2)和富含酸性半胱氨酸的分泌蛋白(骨连接蛋白,SPARC)的时间变化。随着CL的发育,黄体VEGFA浓度升高,但在退化的CL中较低。相反,黄体FGF2浓度在排卵后立即在塌陷卵泡中最高,并随着CL的发育而下降。此外,塌陷卵泡中存在三种FGF2异构体,但在较老的CL中仅检测到一种异构体。有趣的是,FGF2浓度在退化CL中增加。SPARC的蛋白质印迹分析显示存在两种异构体,它们在整个CL发育过程中组成性表达。进一步的研究调查了LH对FGF2的调节作用,结果表明,经历过LH峰的动物排卵前卵泡液中的FGF2浓度较高。此外,LH刺激分散的黄体细胞产生FGF2。相反,LH峰对卵泡液VEGFA浓度没有影响。总之,在卵泡 - 黄体转变过程中,FGF2比VEGFA和SPARC更具动态性,这表明FGF2此时在血管生成起始中起关键作用。此外,这可能是由LH峰刺激的。结果还表明,VEGFA和SPARC在CL脉管系统的发育中具有更具组成性但必不可少的作用。