ELUCIDATION OF REGULATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR EXPRESSION IN THE LUTEAL DEVELOPMENT OF GOATS.

在项目的第一年（2001年），我们检测了羊黄体发育过程中VFGF受体Flk-1和Flt-1基因表达的变化，以阐明VEGF信号系统的调控机制。结果表明，在黄体发育早期，Flk-1基因表达增加，而Flk-1可能参与VEGF信号的转导。然而，Flt-1的基因表达在黄体发育过程中没有变化，而在黄体维持期增加。Flt-1似乎是VEGF的诱饵受体。这些结果表明，在山羊黄体发育过程中，VEGF可能部分通过VEGF受体Flk-1刺激血管生成，并且VEGF的信号转导可能在受体水平上受到调节。为了阐明前列腺素（PG）在羊体黄体发育中的作用，寻找一种早期黄体的回归方法，研究了PG合成酶和PGI_2受体基因表达的变化，以及PG合成酶抑制剂对黄体发育的影响。结果表明，PGI_2受体（IP-R和PPARδ） mrna在黄体发育早期均有升高。此外，结果还表明，在排卵后，PG抑制剂苯丁酮直接进入黄体，可以部分抑制黄体发育，但抑制不完全。上述结果提示PG，特别是PGI_2可能在山羊黄体发育中起一定作用，但尚需进一步研究寻找早期黄体回归的方法。综上所述，本研究提示VEGF受体Flk-1基因表达的增加可能参与了山羊黄体发育时期VEGF信号转导的调控。此外，这些研究表明PGs，特别是PGI_2可能在黄体发育中起作用。少

In the first year of the research project (2001), changes of gene expression of the VFGF receptor, or Flk-1 and Flt-1 were examined during the development of caprine corpora lutea to elucidate any regulation mechanism of VEGF signaling system. The results showed that the gene expression of Flk-1, which seems to play a role for transduction of VEGF signaling, increased in the early stage of the luteal development. However, the gene expression of Flt-1, which seems to act as a decoy receptor for VEGF, did not change during the luteal development and increased in the period of luteal maintenance. These results suggest that VEGF may stimulate angiogenesis partly through a VEGF receptor, Flk-1, during The luteal development in the goat and that the signal transduction of VEGF may be regulated at the level of the receptor.In the second year of the research project (2002), to elucidate roles of prostaglandins (PG) in the development of caprine corpora lutea and to look for a method to regress … More the early corpora lutea, changes of gene expressions ofPG synthases and PGI_2 receptors, and effects of PG synthase inhibitors on luteal development were examined. As the results, it was shown that both mRNAs of the PGI_2 receptors, or IP-R and PPARδ increased in the early stage of the luteal development. Furthermore, the result also showed that the luteal development was partially inhibited by the direct administration of phenylbutazone, a PG inhibitor, into the corpus luteum just after ovulation, but the inhibition was not complete. These results suggest that PG, especially PGI_2, may play roles in the luteal development in the goat, but further studies are required to find a method for regression of the early corpus luteum.In conclusion, the present studies indicate a possibility that the increase of gene expression of a VEGF receptor, Flk-1, may participate in regulation of signal transduction of VEGF in the period of luteal development in goats. Besides, these studies suggest that PGs, especially PGI_2, may play a role in the luteal development. Less