Reply to Liu: Inflammation before implantation both in evolution and development

In a paper in PNAS (1) we show that, in opossums, endometrial inflammation follows attachment of the embryo to the uterine wall. We argue that this is similar to what occurred in the first live-bearing mammals, and that inflammatory signaling seen at implantation in eutherians evolved from this attachment-induced inflammation. In a letter on our paper, Liu (2) presents evidence of endometrial inflammatory gene expression in mice before embryonic attachment. Liu infers that inflammatory signaling at implantation cannot be a consequence of embryonic attachment because inflammation precedes implantation in mice and humans. Liu alternatively proposes that inflammation during implantation in eutherians has evolved because the embryo coopted L-selectin expression, allowing it to “act” like a leukocyte and facilitate endometrial infiltration. This is an interesting hypothesis, because it may explain why inflammatory … [↵][1]1To whom correspondence should be addressed. Email: oliver.griffith{at}yale.edu. [1]: #xref-corresp-1-1