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Determination of Cell Type Specificity and Estrous Cycle Dependency of Monocyte Chemoattractant Protein-1 Expression in Corpora Lutea of Normally Cycling Rats in Relation to Apoptosis and Monocyte/Macrophage Accumulation¹

^a Graduate School of Natural Science and Technology ^b Graduate School of Medical Science, Kanazawa University, Takara-machi, Kanazawa, Ishikawa 920-0934, Japan

In regressive corpora lutea, apoptosis of luteal cells, expression of monocyte chemoattractant protein-1 (MCP-1), and accumulation of monocytes/macrophages occur. However, whether these three events are correlated and what cell type expresses MCP-1 have yet to be determined. To clarify these issues, we performed histochemical examinations to determine the localization and the numbers of MCP-1 mRNA-containing cells, apoptotic cells, and monocytes/macrophages in corpora lutea of normally cycling rats. We found that the Mcp-1 gene is expressed in nonapoptotic steroidogenic luteal cells. Corpora lutea that contained MCP-1 mRNA-expressing cells increased in number at estrus together with those containing apoptotic luteal cells. When individual corpora lutea at estrus were analyzed, those with many MCP-1-expressing cells contained few apoptotic cells, and vice versa. These results collectively suggest the following pathway for apoptosis- and MCP-1-dependent regression of the corpus luteum: 1) luteal cells are induced to undergo apoptosis at estrus, and the activation of Mcp-1 gene expression follows in nonapoptotic luteal cells; 2) monocytes/macrophages are chemoattracted by MCP-1 toward corpora lutea containing apoptotic luteal cells; and 3) monocytes/macrophages invade corpora lutea and eliminate apoptotic luteal cells by phagocytosis.

¹ Supported by the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research), the Sumitomo Foundation, the Honjin Foundation, the Hayashi Memorial Foundation for Female Natural Scientists, and the Japan Science Society.

² Correspondence: Yoshinobu Nakanishi, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920-0934, Japan. FAX: 81 76 234 4480; nakanaka{at}kenroku.kanazawa-u.ac.jp

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