Progesterone during pregnancy: endocrine-immune cross talk in mammalian species and the role of stress

Am J Reprod Immunol. 2007 Sep;58(3):268-79. doi: 10.1111/j.1600-0897.2007.00512.x.


Progesterone is critical for the establishment and the maintenance of pregnancy, both by its endocrine and immunological effects. The genomic actions of progesterone are mediated by the intracellular progesterone receptors; A and B. A protein called P-induced blocking factor (PIBF), by inducing a T(H2) dominant cytokine production, mediates the immunological effects of progesterone. Progesterone plays a role in uterine homing of NK cells and up-regulates HLA-G gene expression, the ligand for various NK inhibitory receptors. At high concentrations progesterone is a potent inducer of Th2-type cytokines as well as of LIF and M-CSF production by T cells. Though a key role for progesterone in creating local immunosuppression has been conserved during the evolution of an epitheliochorial placenta, there has been some divergence in the pattern of endocrine-immunological cross talk in Bovidae. In sheep, uterine serpin, a progesterone-induced endometrial protein, mediates the immunosuppressive effects of progesterone. Epidemiological studies suggest the role of stress in premature pregnancy termination and exposure to stress induces abortion in mice via a significant reduction in progesterone levels, accompanied by reduced serum levels of PIBF. These effects are corrected by progesterone supplementation. These findings indicate the significance of a progesterone-dependent immuno-modulation in maternal tolerance of the fetus, which is discussed in this review.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Endocrine System / drug effects
  • Endocrine System / physiology*
  • Female
  • Humans
  • Immune System / drug effects
  • Immune System / physiology*
  • Mice
  • Pregnancy
  • Pregnancy Outcome
  • Progesterone / pharmacology
  • Progesterone / physiology*
  • Stress, Physiological / metabolism*


  • Progesterone