Cooperative inflammation: The recruitment of inflammatory signaling in marsupial and eutherian pregnancy

Abstract

The evolution of viviparity in therian mammals, i.e. marsupials and "placental" mammals, occurred by retention of the conceptus in the female reproductive tract and precocious "hatching" from the shell coat. Both eutherian embryo implantation and the opossum embryo attachment reaction are evolutionarily derived from and homologous to a defensive inflammatory process induced after shell coat hatching. However, both lineages, marsupials and placental mammals, have modified the inflammatory response substantially. We review the induction, maintenance, and effects of inflammation throughout pregnancy, with special attention to the role of prostaglandins and the mucosal inflammatory response, both of which likely had roles in early mammalian viviparity. We propose that the key step was not only suppression of the inflammatory response after implantation in placental mammals, but also the transfer of the inflammatory cell-cell communication network to a different set of cell types than in generic inflammation. To support this conclusion we discuss evidence that pro-inflammatory signal production in the opossum is not limited to maternal cells, as expected in bona fide defensive inflammation, but also includes fetal tissues, in a process we term cooperative inflammation. The ways in which the inflammatory reaction was independently modified in these two lineages helps explain major life history differences between extant marsupials and eutherians.

Exometabolomic analysis of decidualizing human endometrial stromal and perivascular cells

“…coinciding with the initial inflammatory phase. 13 The secreted response at this time-point was also more pronounced in PVC than EnSC, in keeping with the topology of decidualization in vivo . 4 The PVC exometabolome on day 2 was enriched in higher energy metabolites linked to pyruvate metabolism and TCA cycle, indicative of Warburg effect or active metabolism.…”

“…Recent studies have shown that decidualization is a multistep differentiation process, which starts with an evolutionarily conserved acute cellular stress response, 12,13 characterized by a burst of reactive oxygen species (ROS) production and release of proinflammatory cytokines. 5,14–16 After a lag period of several days, differentiating cells lose their fibroblastic appearance and emerge as secretory decidual cells with abundant cytoplasm and prominent endoplasmic reticulum.…”

Exometabolomic Analysis of Decidualizing Human Endometrial Stromal and Perivascular Cells

“…Recent studies have shown that decidualization is a multistep differentiation process, which starts with an evolutionarily conserved acute cellular stress response ( Erkenbrack et al, 2018 ; Stadtmauer and Wagner, 2020 ), characterized by a burst of reactive oxygen species (ROS) production and release of proinflammatory cytokines ( Al-Sabbagh et al, 2011 ; Salker et al, 2012 ; Brighton et al, 2017 ; Lucas et al, 2020 ). After a lag period of several days, differentiating cells lose their fibroblastic appearance and emerge as secretory decidual cells with abundant cytoplasm and prominent endoplasmic reticulum ( Gellersen and Brosens, 2014 ).…”

Pregnant Females as Historical Individuals: An Insight From the Philosophy of Evo-Devo

“…Immune response in pregnant females would be expected for two reasons: first, because the embryo breaches physical tissue integrity during implantation, and second, because this wounding is caused by a tissue which is immunologically different from the female. However, as there is no maternal rejection of the embryo, traditional approaches have aimed to understand how the expected maternal immune reaction to implantation is “suppressed” by the fetus, for example via the manipulation of progesterone production, thus leading to an “immunological indolence or inertness of the mother” ( Medawar, 1953 ; see Stadtmauer and Wagner, 2020a , b and references therein).…”

“…Besides that, pregnancy needs to be recognized as a reproductive individuality which is irreducible to that of developmental or physiological individuality. Unlike the physiological systems participating in organismic maintenance (such as the digestive, circulatory or respiratory systems), reproductive functionalities are not just contributions to the self- or the scaffolded homeostasis of individual organisms, but to a different type of homeostasis, namely the maintenance of pregnancy as a relational process that might involve different physiological individuals ( Pavličev et al, 2017 ; Stadtmauer and Wagner, 2020a , b ). As a consequence, physiological and reproductive criteria of individuality do not necessarily render the same entities, although they might overlap at certain stages of the life cycle.…”