Tumor Necrosis Factors: Pivotal Components of Pregnancy?1

Tumor necrosis factor alpha is a major component of the infection-stimulated cytokine milieux associated with preterm labor and pregnancy termination. As a consequence, this potent factor is thought by some to have exclusively negative effects on the course of pregnancy. Yet in humans and other mammals, messenger RNA hybridizing with tumor necrosis factor alpha cRNA probes and protein detected by anti-tumor necrosis factor alpha have been identified in normal cycling and pregnant uteri, placentas, and embryos, consistent with an important role for tumor necrosis factor in female reproduction and embryonic development. Here, evidence for this intriguing dichotomy is presented, unresolved aspects are discussed, and potential roles for uteroplacental and embryonic tumor necrosis factor are proposed.