Contrary to widespread belief, the implantation of an embryo for the initiation of pregnancy is like a battle, in that the embryo uses a variety of coercive tactics to force its acceptance by the endometrium. We propose that embryo implantation involves a three-step process: (1) identification of a receptive endometrium; (2) superimposition of a blastocyst-derived signature onto the receptive endometrium before implantation; and finally (3) breaching by the embryo and trophoblast invasion, culminating in decidualization and placentation. We review here the story that is beginning to emerge, focusing primarily on the cells that are in "combat" during this process.

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Immune cell dysregulation and lymphopenia characterize COVID‐19 pathology in moderate to severe disease. While underlying inflammatory factors have been extensively studied, homeostatic and mucosal migratory signatures remain largely unexplored as causative factors. In this study, we evaluated the association of circulating IL‐6, soluble mucosal addressin cell adhesion molecule (sMAdCAM), and IL‐15 with cellular dysfunction characterizing mild and hypoxemic stages of COVID‐19. A cohort of SARS‐CoV‐2 infected individuals (n = 130) at various stages of disease progression together with healthy controls (n = 16) were recruited from COVID Care Centres (CCCs) across Mumbai, India. Multiparametric flow cytometry was used to perform in‐depth immune subset characterization and to measure plasma IL‐6 levels. sMAdCAM, IL‐15 levels were quantified using ELISA. Distinct depletion profiles, with relative sparing of CD8 effector memory and CD4+ regulatory T cells, were observed in hypoxemic disease within the lymphocyte compartment. An apparent increase in the frequency of intermediate monocytes characterized both mild as well as hypoxemic disease. IL‐6 levels inversely correlated with those of sMAdCAM and both markers showed converse associations with observed lympho‐depletion suggesting opposing roles in pathogenesis. Interestingly, IL‐15, a key cytokine involved in lymphocyte activation and homeostasis, was detected in symptomatic individuals but not in healthy controls or asymptomatic cases. Further, plasma IL‐15 levels negatively correlated with T, B, and NK count suggesting a compensatory production of this cytokine in response to the profound lymphopenia. Finally, higher levels of plasma IL‐15 and IL‐6, but not sMAdCAM, were associated with a longer duration of hospitalization.