Estrogen withdrawal induces macrophage invasion in the rabbit corpus luteum

Macrophages within the corpus luteum are associated with spontaneous luteal regression in a number of species. However, an understanding of the consequences of macrophage recruitment on the functional capacity and responsiveness of the luteal tissue has remained elusive. Here we investigate the temporal appearance of macrophages and their potential impact in corpora lutea of rabbits, in which a rapid fall in progesterone synthesis and premature regression of the corpus luteum are initiated by withdrawal of the luteotropic hormone estradiol-17beta. Removal of estradiol implants, placed subcutaneously, induced a significant increase in the average number of macrophages per high-power field (hpf) in corpora lutea (p < 0.05) within 72 h. Replacement of the estradiol implants 48 h after their removal resulted in a marginal rebound of plasma progesterone and a variable number of luteal macrophages (range: 6-160 macrophages/hpf) among the 11 rabbits. A third experiment revealed that the relative numbers of macrophages within the corpora lutea have no apparent relationship to rates of progesterone synthesis in vitro: progesterone production (ng/mg tissue) did not differ (p > 0.05) between corpora lutea of estradiol-maintained rabbits and those of estradiol-replaced rabbits despite obvious differences in numbers of luteal macrophages (2 +/- 1 vs. 42 +/- 10 macrophages/hpf, respectively; p < 0.05). We conclude that the entry/recruitment of macrophages into the rabbit corpus luteum is sensitive to the luteotropic hormone estradiol-17beta and that the presence of macrophages does not preclude the continuation of progesterone production in surviving luteal tissue revitalized after estradiol removal/replacement.