Regulation of Numbers of Macrophages in the Endometrium of the Sheep by Systemic Effects of Pregnancy, Local Presence of the Conceptus, and Progesterone

Abstract

Many species exhibiting hemochorial placentation experience an accumulation of macrophages in the endometrium during pregnancy. For the present study, it was tested whether macrophages also accumulate in the endometrium of the sheep, which is a species undergoing an epitheliochorial placentation. An additional objective was to determine whether regulation of endometrial macrophage number occurs via systemic or local signals and whether progesterone is one of these signals. The approach was to evaluate presence of macrophages immunohistochemically using antibodies to CD68 and CD14. Tissues examined were from cyclic ewes in the luteal phase of the estrous cycle, unilaterally-pregnant ewes at day 140 of pregnancy in which pregnancy was surgically confined to one uterine horn, ovariectomized ewes, and ovariectomized ewes treated with progesterone for 44 days. Macrophages were localized predominately to the stromal compartment of the stratum compactum region of the endometrium. In non-pregnant ewes, macrophages were not abundant regardless of physiological status. Increased numbers of endometrial macrophages were seen for both the pregnant and non-pregnant uterine horns of unilaterally pregnant ewes. Numbers of macrophages were higher in the endometrium from the pregnant uterine horn than from endometrium from the non-pregnant uterine horn. Results indicate that macrophages accumulate in the endometrium by day 140 of pregnancy in the sheep and that this induction is because of both systemic and local signals. Progesterone appears not to be an important regulator of numbers of endometrial macrophages.

Deviations in populations of peripheral blood mononuclear cells and endometrial macrophages in the cow during pregnancy

“…An increase in the relative number of gdT cells in peripheral blood 3 weeks before parturition followed by decrease to initial values at the time of parturition has been noted by others (Van Kampen & Mallard 1997). The recruitment of macrophages to the pregnant uterus has been described in many species such as humans (Heikkinen et al 2003, Cupurdija et al 2004, Kim et al 2007), mice (Hunt et al 1985), and sheep (Tekin & Hansen 2004). Present results indicate that this process occurs in the cow also with numbers increasing by days 54-100 of pregnancy.…”

“…Thus, the maternal immune system in the cow is constantly adjusting to the conceptus. Given this pattern of immunological change, which is also seen in other species with epitheliochorial placenta (Lee et al 1992, Yu et al 1993, Baker et al 1999, Majewski et al 2001, Tekin & Hansen 2004, it seems more likely that evolution of a epitheliochorial placenta occurred because of increases in efficiency of placental transport (Leiser et al 1997) or increased maternal control over the vascular supply to the conceptus (Mess & Carter 2007) rather than to change the fundamental characteristics of the maternal-fetal immunological relationship.…”

“…There is some evidence, however, that the immunological adjustments to pregnancy in species with epitheliochorial placentation are similar to those seen in the mouse and human. In the sheep, for example, pregnancy is associated with an increase in the number of macrophages in stroma (Tekin & Hansen 2004) and in the number of gdT cells in the luminal epithelium and immediately adjacent stroma (Lee et al 1992, Majewski et al 2001. There is evidence for specific downregulation of maternal cytotoxic lymphocytes towards paternal antigens in pregnant mares (Baker et al 1999), and there is accumulation of cells with NK activity during early pregnancy in the pig (Yu et al 1993).…”

Immunoendocrine aspects of endometrial function and implantation

“…Nevertheless, in the ovine uterus, low concentrations of progesterone can block tissue graft rejection (Majewski & Hansen 2002, and this has been associated with the induction of a uterine immunoregulatory protein belonging to the serpin family of proteinase inhibitors (see later). The accumulation of macrophages and gd T-cells in the ovine uterus during pregnancy also appears to be partly under sex steroid regulation (Tekin & Hansen 2004).…”

Developing a conceptual model of possible benefits of condensed tannins for ruminant production

“…The γδ T-cells populate the blood and usually enrich lymphatic tissues, lungs, skin, reproductive tract and small intestine epithelia. Immune-physiological reproductive evidence suggests that increased numbers of γδ T-cells in endometrial luminal epithelium are not only dependent upon conceptus stimulus (Tekin and Hansen, 2004) but also on systemic signals (i.e. maternal blood circulation; Majewski et al, 2001;Oliveira et al, 2012).…”