Inflammation in the endometrium of the tammar wallaby (Macropus eugenii) at the time of birth.

graphical abstractABSTRACT: Pregnancy involves inflammatory processes, and the endometrium is populated by a range of immune cells whose functions depend on pregnancy length, species and placentation type. In eutherians, prolonged embryo-maternal contact during placentation implies mechanisms of immune tolerance to the semi-allogeneic fetus. However, at the time of birth, inflammatory processes prevail. Marsupials provide an opportunity to identify mechanisms of placentation and parturition in a lineage separate from that of eutherian mammals. Here, we identified and quantified crucial immune cells in the tammar wallaby endometrium in gravid and nongravid uteri at term. Neutrophils and T cells were labeled with anti-myeloperoxidase (MPO) and anti-CD3, respectively, and were counted manually. Automated cell counts were used to quantify macrophages stained with Perls' Prussian blue stain. The yolk sac, which represents the embryonic part of the placenta, was morphologically described by light microscopy. In the gravid endometrium, we found significantly more MPO-positive neutrophils and CD3+ T cells than in the nongravid endometrium, whereas macrophages were significantly more abundant in the non-gravid endometrium. Embryonic trophoblast giant cells showed fringed margins, vacuolated cytoplasm, and degenerating nuclei. We conclude that the inflammatory processes observed at the time of birth are likely to be a sterile inflammation triggered by the aging and deteriorating embryonic trophoblast, which might be a limiting factor for the short marsupial pregnancy. Our findings present a base model for understanding the evolution of maternal-fetal immune interactions and the induction of birth. LAY SUMMARY: During mammalian pregnancy, the mother's immune system could treat the embryo as foreign because it expresses antigens inherited from the father. In eutherian mammals, such as humans, which have longer pregnancies than marsupials, this immune response is suppressed until the onset of birth. Marsupials, such as the tammar wallaby, have a restricted period of embryo-maternal contact. We compared the amount of different immune cells in the pregnant and nonpregnant uteri of tammar wallabies at the time of birth. We found that neutrophils, which are part of the nonspecific immune system, were the predominant cell type in the uterus carrying the embryo. Together with the degeneration of placental cells that we observed, these findings suggest that marsupial birth is preceded by a nonspecific inflammatory response triggered by the aging placenta rather than an adverse specific reaction against the fetus. Our study contributes to the understanding of the evolution of the immune environment that supports live birth.