title: 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.
  
  
  BACKGROUND
  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.
authors.affiliation: a Department of Pharmaceutical Sciences , Suzuka University of Medical Science , Suzuka , Mie , Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hiramoto
authors.affiliation: a Department of Pharmaceutical Sciences , Suzuka University of Medical Science , Suzuka , Mie , Japan.
authors.forename: Yurika
authors.initials: Y
authors.lastname: Yamate
authors.affiliation: a Department of Pharmaceutical Sciences , Suzuka University of Medical Science , Suzuka , Mie , Japan.
authors.forename: Eisuke F
authors.initials: EF
authors.lastname: Sato
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D005260:Female; D005298:Fertility; D005838:Genotype; D005865:Gestational Age; D007070:Immunoglobulin A / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008098:Litter Size; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018396:Mucin-1 / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D010641:Phenotype; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014599:Uterus / Q000201:enzymology*
chemical_list: C587672:IL1B protein, mouse; D007070:Immunoglobulin A; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D018396:Mucin-1; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; C118370:interleukin-18 binding protein; C577056:muc1 protein, mouse; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D020170:Caspase 1
keywords: Gp91phox; interleukin-18; mucin1; reactive oxygen species