Effects of vasoactive substances on ovarian function and implantation in the molecular biological approach

本研究旨在探讨血管内皮细胞衍生的血管活性物质，即一氧化氮(NO)/一氧化氮合酶（NOS）系统和一氧化碳(CO)/血红素加氧酶（HO）系统对性激素诱导的分泌期人子宫内膜细胞和着床期人蜕膜细胞分化的影响。并主要应用分子生物学方法对猪颗粒细胞的卵泡发育或黄体生成进行了研究。这些研究表明，由iNOS局部合成的NO可能参与子宫内膜功能的调控，NO/NOS系统在维持妊娠中发挥重要作用。此外，CO/HO系统可能在正常月经期子宫内膜功能的局部控制中发挥作用。CO/HO还可能参与控制胎盘血管功能，保护合胞滋养细胞和内皮细胞免受氧化损伤。在卵巢功能方面，这些结果表明，在中等成熟的PGC中，NO通过抑制P450芳香化酶活性来抑制E2的独立于cGMP的分泌，并强烈提示PGC中的NO/NOS系统在卵泡发育的不同阶段对甾体生成的调节不同。另一方面，我们认为CO/HO系统催化反应的产物可能是调节PGC细胞凋亡的重要自分泌/旁分泌因子。

The aim of the present study was undertaken to investigate some vasoactive substances derived from vascular endotherial cells, namely the nitric oxide(NO)/NO synthase(NOS) system and the carbon monoxide (CO)/heme oxygenase (HO) system, on the differentiation induced by sex steroid hormones in human endometrial cells of the secretory phase and human decidual cells in implantation, and on the follicular development or luteinization in porcine granulose cells by mainly using molecular biological methods. These studies reveal that NO locally synthesized by iNOS could be involved in the control of endometrial functions, and NO/NOS system play an important role in the maintenance of pregnancy. Furthermore, it is suggested that the CO/HO system possibly play a role in the local control of endometrial function in normal menstrual periods. CO/HO may also be involved in the control of placental vascular function, which protect the syncytiotrophoblast and endothelium against oxidative injury. In ovarian functions, these results demonstrate that NO inhibits E2 secretion independent of cGMP by inhibiting P450 aromatase activity in moderately mature PGC, and strongly suggest that the NO/NOS system in PGC regulates steroidogenesis differently during different phase of follicular development. On the other hand, we conclude that products of reactions catalyzed by CO/HO system are likely to be important autocrine/paracrine factors that regulate apoptosis in PGC.