A pronounced uterine pro-inflammatory response at parturition is an ancient feature in mammals

Abstract

Regulating maternal immunity is necessary for successful human pregnancy. Whether this is needed in mammals with less invasive placentation is subject to debate. Indeed, the short gestation times in marsupials have been hypothesized to be due to a lack of immune regulation during pregnancy. Alternatively, the maternal marsupial immune system may be unstimulated in the absence of a highly invasive placenta. Transcripts encoding pro-inflammatory cytokines were found to be overrepresented in the whole uterine transcriptome at terminal pregnancy in the opossum, To investigate this further, immune gene transcripts were quantified throughout opossum gestation. Transcripts encoding pro-inflammatory cytokines remained relatively low during pre- and peri-attachment pregnancy stages. Levels dramatically increased late in gestation, peaking within 12 h prior to parturition. These results mirror the spike of inflammation seen at eutherian parturition but not at attachment or implantation. Our results are consistent with the role of pro-inflammatory cytokines at parturition being an ancient and conserved birth mechanism in therian mammals.

Multiomic immune clockworks of pregnancy

“…In nonhuman primates, inflation of a balloon within the amniotic cavity increased maternal plasma interleukin (IL)-1β, tumor necrosis factor (TNF)α, IL-8, and IL-6 and prompted uterine contractions [188]. It is well known that these pro-inflammatory cytokines TNFα and IL-1β and production of prostaglandins are strongly associated with active labor in both mice and humans [65,67,106,151].…”

Recent advances in understanding evolution of the placenta: insights from transcriptomics

“…Transcriptomic analysis has thrown new light on the evolution of the decidualization process 63 , 64 . Kin et al .…”

“…In an extension of this work, transcriptomic data were used to explore differences and similarities between the decidual response and the inflammatory response 68 , 69 . It was shown for the opossum that the brief period of attachment between fetal membranes and the uterus was characterized by expression of the full repertoire of genes characterizing the inflammatory response 63 , 69 . In eutherians, on the other hand, some components were missing.…”

Immune Regulation in Eutherian Pregnancy: Live Birth Coevolved with Novel Immune Genes and Gene Regulation

“…This is followed by the formation of the placenta (Figure b), which serves nutritive and immune‐modulatory roles for the remainder of the pregnancy. Conserved sets of inflammatory markers and immune pathways are involved in both eutherian implantation and marsupial attachment and labor . However, in contrast to marsupials, eutherians experience major switches in the overall activities of the immune system in the uterus during pregnancy: the upregulation of inflammation in the uterus during implantation is followed by an extended anti‐inflammatory period (Figure b), which likely stems from the need to protect the developing fetus from detrimental immune responses.…”

“…Conserved sets of inflammatory markers and immune pathways are involved in both eutherian implantation and marsupial attachment and labor. [5,9] However, in contrast to marsupials, eutherians experience major switches in the overall activities of the immune system in the uterus during pregnancy: the upregulation of inflammation in the uterus during implantation is followed by an extended anti-inflammatory period [5,10] (Figure 1b), which likely stems from the need to protect the developing fetus from detrimental immune responses. Toward the end of pregnancy, the eutherian uterus experiences a spike in inflammation yet again, resulting in the initiation of labor.…”