Prostaglandin E2 and Nitric Oxide production by paternal and maternal inherited iNOS in placental tissue in iNOS knockout mice treated with LPS

Abstract

MATERNAL INHERITED INOS IN PLACENTAL TISSUE IN INOS KNOCKOUT MICE TREATED WITH LPS HIDENORI TAKAHASHI, TOSHIAKI OKAWA, KEIYA FUJIMORI, AKIRA SATO, YURI VEDERNIKOV, GEORGE SAADE, ROBERT GARFIELD, Fukushima Medical University, Obstetrics & Gynecology, Fukushima, Japan, University of Texas Medical Branch at Galveston, Obstetrics & Gynecology, Galveston, Texas OBJECTIVE: To evaluate the effect of paternal or maternal iNOS on prostaglandin E2 (PGE2) and Nitric Oxide (NO) production by placental tissue of pregnant iNOS knockout (iNOSKO) mice and their control mice (C3HeN:C3H) treated with lipopolysaccharide (LPS). STUDY DESIGN: Nonpregnant (NonPreg) iNOSKO(iNOS / ) and C3H(iNOSC/C) and Pregnant (Preg) mice with genetic composition of placenta for mating as (A) male iNOSKO! female iNOSKO; iNOS / , (B) male iNOSKO! femaleC3H; iNOS /Cm, (C) male C3H! female iNOSKO; iNOSCp/ mice on day 14 of gestation were sacrificed 6 hours after intraperitoneal (i.p.) injection of LPS (400 mg/kg) or vehicle (n=8 per group). Uterine rings from NonPreg and Preg were equilibrated in Krebs-Henseleit solution. In some rings from Preg, a piece of placenta was left attached to the uterine wall. One ml sample of the solution was taken after 60 min incubation. The sample was analyzed for PGE2 by radioimmunoassay and NOx production. Statistical analysis was performed using one way ANOVA. RESULTS: (1) PGE2 Production: LPSsignificantly increased PGE2 production in both NonPreg C3H and iNOSKO mice compared without LPS. LPS also increased in placenta attached uterine tissue of all 3 types as (A), (B) and (C). (2)NOx Production: In NonPreg uterine tissue, LPS significantly increased NOx production in both C3H and iNOSKO mice. In Preg placentai tissue, increasing order of magnitude of NOx production without LPS; (A) iNOS( / ) =(C) iNOS ( /Cm)! (B) iNOS(Cp/ ) (p!0.05). LPS significantly increased NOx production in (C) (p!0.01), however, significantly decreased in (B) (p!0.05) and did not change in (A) compared without LPS. CONCLUSION: LPS, a crucial mediator of inflammation and infection, induced PGE2 and NOx production of uterine tissue in NonPreg mice independent of iNOS. However, in Preg mice then presense of the placenta with paternal iNOS decreased NOx production. This study indicates that physiological and pathophysiological iNOS in placental tissue originate from paternal and maternal tissue respectively.