Title of Project ; Analysis of differentiation of human luteal cells, using monoclonal antibodies that recognize differentiation-related antigens on luteal cells.

研究结果黄体在女性生殖过程中具有重要的生理功能。人们普遍认为，黄体是成功怀孕所必需的。黄体功能障碍被认为是不孕和/或习惯性流产的原因之一，此外，黄体功能不全可能导致子宫内膜增生和子宫内膜癌。此外，在黄体期，黄体细胞表现出形态和功能的变化。在CL形成过程中，卵泡细胞向黄体细胞分化，类固醇生成酶被诱导产生孕酮等，在CL消退过程中，黄体细胞出现凋亡变化。因此，黄体细胞是分析细胞分化的有用材料。为了探讨人卵巢黄体细胞的分化途径及其调控机制，我们采用小鼠单克隆抗体， ...更多信息 抗体（mAbs），并分析了细胞谱系和分化阶段特异性表达的细胞表面分子。(1)我们已经获得了几个单克隆抗体，识别颗粒细胞系特异性或卵泡膜细胞系特异性细胞表面分子。从这些数据中，我们提出了人颗粒细胞分化为大黄体细胞的月经CL和CL的早孕，和人卵泡内膜细胞分化为小黄体细胞。(2)我们发现月经期CL和妊娠期CL中有几种分子的表达谱是不同的。提示妊娠期CL与周期性CL具有不同的功能。(3)通过研究促性腺激素和细胞因子对黄体细胞分化相关抗原表达的影响，发现黄体细胞的分化不仅受促性腺激素的调节，还受细胞因子的调节。提示免疫因素参与了月经期CL与妊娠期CL的分化。(4)我们发现，整合素（细胞粘附分子）和细胞外基质之间的相互作用是黄体细胞分化的局部调节因子。少

Summary of Research ResultsCorpus luteum (CL) has important physiological functions in the female reproduction. It is generally accepted that corpus luteum is essential for successful pregnancy. Luteal dysfunction is assumed to be one of causes of infertility and/or habitual abortion.In addition, it is suggested that luteal insufficiency may cause endometrial hyperplasia and cancer. Furthermore, during the luteal phase, luteal cells show morphological and functional changes. During the CL formation, follicular cells differentiate to luteal cells, and steroidogenic enzymes are induced to produce progesterone and so on. During the CL regression, luteal cells demonstrate apoptotic changes. Therefore, luteal cells are useful materials for analysis of cell differentiation. However, differentiation of luteal cells are not understood, to date.To investigate the differentiation pathways and regulatory mechanisms of differentiation of human luteal cells in the ovary, we raised murine monoclonal … More antibodies (mAbs) against human luteal cells, and analyzed the cell-lineage-and differentiation stage-specifically expressed molecules on cell surface. (1) We have obtained several mAbs that recognize granulosa cell lineage-specific or thecal cell lineage-specific cell surface molecules. From these data, we proposed the human granulosa cells differentiate to large luteal cells of the menstrual CL and also CL of early pregnancy, and that human theca interna cells differentiate to small luteal cells. (2) We have found expression profiles of several molecules are different between the menstrual CL and CL of pregnancy. This suggest that CL of pregnancy have different functions from CL of the cycle. (3) Though the study on the effect of gonadotropins and cytokines on the expression of the differentiation-related antigens on luteal cells, we have found that differentiation of luteal cells are regulated not only by gonadotropins but also by cytokines. This suggests that immunological factors are involved in the differentiation of menstrual CL to CL of pregnancy. (4) We have found that the interaction between integrins (cell adhesion molecules) and extracellular matrices are local regulator of the differentiation of luteal cells. Less