Molecular hydrogen has a positive impact on pregnancy maintenance through enhancement of mitochondrial function and immunomodulatory effects on T cells

Aims: Molecular hydrogen (H-2) has attracted growing interest because of its implications in various diseases. However, the molecular mechanisms underlying the remarkable effect of a small amount of H-2 remain elusive. No knowledge has been available on the role of H-2 in the etiology of pregnancy disorders or its direct influence on human immune cells. Since maternal immunity, T cells in particular, plays a critical role in pregnancy maintenance. We investigated the effects of H-2 on T cells and its relation to preterm birth (PTB). Main methods: Exhaled H-2 concentrations in pregnant women were measured and correlated with cytokine concentrations in maternal and umbilical cord blood. H-2 was added to T cells collected from healthy donors, and differentiation and proliferation were examined. Energy metabolism was also examined. H-2 was administered to mice and cytokine expression was compared. Key findings: Our prospective observational study revealed that maternal production of H-2 is significantly lower in pregnant women with PTB, suggesting its potential as a biomarker for predicting PTB. We found that H-2 has clear associations with several maternal cytokines, and acts as an immunomodulator by exerting mitochondrial function in human T cells. Moreover, in vivo administration of H-2 to pregnant mice regulated inflammatory responses and reduced PTB caused by T cell activation, which further supports the notion that H-2 may contribute to prolonged gestation through its immunomodulatory effect. Significance: Measuring maternal H-2-production could be a potential clinical tool in the management of PTB, and H-2 may have positive impact on pregnancy maintenance.