Estrogen withdrawal Induces Macrophage Invasion in the Rabbit Corpus Luteum1

Abstract

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.

Progesterone on an oestrogen background enhances prolactin-induced apoptosis in regressing corpora lutea in the cyclic rat: possible involvement of luteal endothelial cell progesterone receptors

“…Conversely, in this study, large numbers of apoptotic cells without any changes in the macrophage population were present at short times after PRL treatment. This agrees with previous studies in different species that suggested that the mere presence of increased numbers of macrophages is not enough to induce luteal cell death (Naftalin et al 1997, Gaytán et al 1998.…”

Cell death induced by serum deprivation in luteal cells involves the intrinsic pathway of apoptosis

“…There is ample evidence that macrophage invasion and phagocytosis of the apoptotic bodies takes place in regressing corpora lutea (Hehnke et al 1994, Townson et al 1996, Gaytan et al 1997, Naftalin et al 1997, Bowen et al 1999. Thus, because primary cultures of rat macrophages are feasible (Sugino et al 1996), and rat macrophage cell lines are available (Rao et al 2002), it seems reasonable to perform experiments in which transformed luteal cells are induced to die by serum deprivation in the presence of autologous macrophages.…”

Possible Actions of Tumor Necrosis Factor-.ALPHA. in Ovarian Function

“…Since it has been shown that high concentrations of ET-1 decrease P 4 production of bovine luteal cells [48], TNFα-induced ET-1 secretion from the endothelial cells may act on luteal cells as an anti-steroidogenic agent in the CL concomitant with endometrial PGF2α in cattle. Moreover, PGF2α-induced steroid reduction results in the activation of inflammatory cells followed by TNFα and interferon-γ (IFNγ) secretion in the CL of cows [49], pigs [50], and rabbits [51]. TNFα in combination w ith IFNγ reduces P4 production and the num ber of via ble cells , although TNFα alone shows little, if any, effect [33,52].…”

“…The number of leukocytes increases at the time of luteolysis in the CL [49][50][51]. Interactions between TNFα and IFNγ are also considered to be important in the structural regression of the CL.…”

“…Interactions between TNFα and IFNγ are also considered to be important in the structural regression of the CL. A decrease in the P4 level and interruption of growth factor signaling in the CL may promote activation of inflammatory cells resulting in increased TNFα and IF Nγ p r odu c ti on [50,51 ]. T N Fα in du c es a significant increase in the expression of major histocompatibility (MHC) class I glycoproteins in cultured bovine luteal cells [33].…”