Luteal regression in the normally cycling rat: Apoptosis, monocyte chemoattractant protein-1, and inflammatory cell involvement

In hypophysectomized rats, prolactin induces regression of the corpora lute a. Luteal regression is accompanied by infiltration of monocytes/macrophage s, declines in luteal mass and plasma progestins, and increased staining fo r monocyte chemoattractant protein-1 (MCP-1). We investigated whether simil ar events are induced during the estrous cycle, after the proestrous prolac tin surge. Rats were killed on proestrus or on estrus, and one ovary was fr ozen for immunohistochemical detection of MCP-1, monocytes/macrophages (ED1 -positive), and differentiated macrophages (ED2-positive) and for in situ d etection of apoptotic nuclei. Corpora lutea of the current (proestrus) or p receding (estrus) cycle were dissected from the ovaries of additional rats and frozen for the same analyses and for determination of total protein con tent. In sections of whole ovaries, intensity and distribution of MCP-1 sta ining were increased in corpora lutea of multiple ages on estrus as compare d to proestrus, as were numbers of differentiated macrophages and apoptotic nuclei per high-power field. Sections of isolated corpora lutea showed the se increases on estrus, and the number of monocytes/macrophages per high-po wer field was also significantly increased. Accompanying these inflammatory /immune events, the corpora lutea on estrus showed decreased weight and tot al protein per corpus luteum, as compared to corpora lutea on proestrus. Th ese changes are consistent with a proposed role for prolactin in the initia tion of luteal apoptosis and of a sequence of inflammatory/immune events th at accompany regression of the rat corpus luteum during the normal estrous cycle.