Meeting Abstract
Embryo implantation is the first step in the establishment of pregnancy in eutherian (placental) mammals. Although pregnancy arose before the common ancestor of marsupials and eutherians (Theria), implantation is unique to Eutheria. The ancestral therian pregnancy likely involved a brief fetal-maternal attachment followed by birth rather than implantation, as in many marsupials. Here, we elucidate the evolutionary mechanism by which the ancestral fetal-maternal attachment was transformed into implantation. We used transcriptomics and immunohistochemistry of uteri of four eutherians – armadillo, hyrax, tenrec, and rabbit; and a marsupial outgroup, opossum. This allows inference of the eutherian ancestral state. Our results show that implantation evolved from an ancestral inflammatory response, a natural uterine reaction to the fetus when pregnancy arose in Theria. In Eutheria, this inflammation was domesticated such that the fetal-maternal attachment results in embryo implantation rather than birth. This was achieved by retaining components of the inflammatory response beneficial to placentation (angiogenesis, vascular permeability); while blocking the detrimental neutrophil infiltration through suppression of IL17A cytokine signaling. Using in vitro experiments, we show that the suppression of IL17A signaling was caused by uterine decidual cells, a novel cell-type in Eutheria. These results provide a mechanistic understanding of the early evolution of eutherian pregnancy, and also identify the ancestral function of an evolutionary novelty, the decidual cell-type.
