Cytokines modulate preimplantation development and pregnancy.

Using two different models of pregnancy failure in mice, we show in this communication that preimplantation embryonic development can be controlled, in vivo, with cytokines. In one model, described by us previously, CSF-1 is shown to block gestations in plugged females due to its induction of defective early development. Pregnancies and preimplantation development are shown here to be restored to normal by TNF alpha or GM-CSF but not by TGF beta 1. In the second model, we reveal that CBA/J females plugged by various male strains produce spontaneously an extremely high proportion of abnormal precompaction embryos. Normal morulae and blastocysts, able to further develop and implant in vitro, are shown here to be induced by TNF alpha and to a lesser extent by GM-CSF and IL-1 alpha. These results suggest strongly that cytokines are potent modulators of early development. They may provide new and interesting insights into early events of mammalian embryonic development.