Gp91phox NADPH oxidase modulates litter size by regulating mucin1 in the uterus of mice

Abstract

Active oxygen derived from gp91phox is critical for gestation. However, no reports have evaluated the relationship between reactive oxygen species (ROS) and the number of births in a given pregnancy. In this study, we examined the influence of ROS produced by gp91phox activity on the number of births using C57BL/6j (control) and gp91phox-knockout (gp91phox−/-) mice. The number of births in gp91phox−/- mice was found to be lower than that in control mice. We observed sequential increases in gp91phox, ROS, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), caspase-1, and interleukin-18 (IL-18), followed by increased expression of mucin1 (MUC1), in control mice. However, none of these markers were upregulated in gp91phox−/- mice. In addition, in control mice administered IL-18 or MUC1 inhibitors, the number of births decreased to a number similar to that of gp91phox−/- mice. These results suggest that ROS derived from gp91phox activity altered the inflammatory system and produced IL-18, which subsequently increased the expression of MUC1, thereby modulating fetal development. Abbreviations: IL-1 β: interleukin-1β; IL-18: interleukin-18; NLRP3: nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3; IgA: immunoglobulin A; MUC1: mucin1