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The Role of the Active Oxygen Produced from Gp91phox NADPH Oxidase on the Newborn Weight of Mouse Pups

Keiichi Hiramoto, Yurika Yamate, Takuji Shirasawa and Eisuke F. Sato

It is known that active oxygen plays an important role in a reproduction. However, no report has so far investigated the influence of active oxygen produced from gp91phox NADPH oxidase on newborns. In this study, we investigated the influence of active oxygen on the weight of newborns using graviditas gp91phox-knockout (gp91phox-/-) mice. Gestational C57BL/6j (control), gp91phox-/-, and insulin-like growth factor-1-knockout (IGF-1-/-) mice were examined and the weight of the newborn mouse pups were analyzed. Gp91phox-/- and IGF-1-/- mouse pups had low weight compared with control mice. When the control mice were treated with an inhibitor of reactive oxygen species (ROS), the newborn weight decreased. Conversely, when the gp91phox-/- mice were treated with an activator of ROS, the newborn weight increased, however, it remained low in the IGF-1-/- mice. Moreover, there were decreased levels of IL-1 in the plasma of graviditas gp91phox-/- mice compared with control and IGF-1-/- mice. Treatment with an IL-1 receptor antagonist in the control mice resulted in a low newborn weight, similar to the gp91phox-/- and IGF-1-/- mice. Furthermore, the expression of NLRP3 and caspase-1 in the uterus of graviditas gp91phox-/- mice was low compared with the control and IGF-1-/- mice. These results clearly indicate that gp91phox NADPH oxidase produces ROS during graviditas. The ROS activate NLRP3, and NLRP3 leads to the production of caspase-1, which subsequently increases IL-1, thereby finally inducing IGF-1. Because the newborn weight is determined by IGF-1, gp91phox appears to be important for promoting fetal growth during graviditas