Many ingredient of the inflammatory response appear to play roles in the process of implantation. Cytokine secretion from the lymphocyte infiltrate in the endometrium activates cellular lysis of trophoblast, perhaps an important process in limiting invasion. Other suppressor cells are present to inhibit the maternal immune response to the implanting embryo. Autocrine/paracrine factors which have been identified in both trophoblast and endometrium include interleukin-2 and colony stimulating factor-1 (CSF-1).

Invasion by the trophoblast is limited by the formation of the decidual cell layer in the uterus. Fibroblast-like cells in the stroma are transformed into glycogen and lipid-rich cells. In the human, decidual cells surround blood vessels late in the nonpregnant cycle, but extensive decidualization does not occur until pregnancy is established. Ovarian steroids govern decidualization, and in the human a combination of estrogen and progesterone is critical. In animals, implantation is preceded by an increase in uterine stromal capillary permeability at the precise site where the blastocyst will attach. The localized nature of this reaction and of decidualization in rodents raises the possibility that a signal from the embryo might be an important triggering stimulus. Thus, maternal recognition of and preparation for pregnancy may depend upon receiving signals released by the embryo.
Boving suggested that the release of CO2 by the embryo in the form of bicarbonate raises the pH of the embryo surface, which, in turn, increases its stickiness. CO2 may also act as a signal to induce a decidual response in the mother.

Histamine may initiate the decidual response. Antihistamines given systemically or directly into the uterus prevent the decidual response in rats. This was disputed when other workers found that systemic antihistamines were not effectual in preventing the decidual response. However, there are two different receptors for histamines, HI and H2. These are not blocked by the same agents, and early experiments demonstrating a lack of effect of antihistamines may have utilized only a block to one receptor. Blockage of both receptors in rats is follittleed by a decrease in the number of implantation sites. Mast cells in the uterus are a major source of histamine, but it is possible that the embryo can also synthesize histamine. This would explain why the increase in capillary permeability and decidualization in the endometrium is localized to areas near the implanting embryo.