Heme oxygenase is downregulated in stress-triggered and interleukin-12-mediated murine abortion

Abstract

Heme oxygenases (HOs) are responsible for heme degradation. Besides their enzymatic activities, HOs are involved in tissue protection. Failing upregulation of HOs has been linked to increased necrosis in inflammatory tissues. Interestingly, previously published data indicated that mice exposed to sonic stress during early gestation show an augmented production of decidual inflammatory T-helper 1 (Thl) cytokines, thus resulting in increased abortion rate. No data linked the Thl-inducer interleukin (IL)-12 with the event of abortion. As little is known about the role of HO in pregnancy maintenance, we evaluated the expression of decidual and placental HO-1 and HO-2 in the abortionprone murine mating combination CBA/J x DBA/2 J with (1) CBA/J female control mice, (2) CBA/J mice exposed to stress during early gestation and (3) CBA/J females injected with recombinant IL-12. Decidual and placental HOs protein expression was analysed by immunohistochemistry and mRNA levels by real time polymerase chain reaction (PCR). As expected, an increased abortion rate was present in mice exposed to stress compared with the control. IL-12 injections also boosted the abortion rate compared with control mice, mimicking the effect of stress. HOs' proteins could be detected in placenta and decidua. Real time PCR revealed lower levels of HO-1 and HO-2 mRNA in stress-triggered and IL-12-injected mice. We conclude that increased Thl-cytokine levels during murine pregnancy may result in low expression of HO-1 and HO-2, thus leading to placental necrosis and foetal rejection.