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Influence of progesterone on myometrial contractility in pregnant mice treated with lipopolysaccharide
Author(s) -
Anbe Hiroshi,
Okawa Toshiaki,
Sugawara Noboru,
Takahashi Hidenori,
Sato Akira,
Vedernikov Yuri P.,
Saade George R.,
Garfield Robert E.
Publication year - 2007
Publication title -
journal of obstetrics and gynaecology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 50
eISSN - 1447-0756
pISSN - 1341-8076
DOI - 10.1111/j.1447-0756.2007.00653.x
Subject(s) - nitric oxide , medicine , endocrinology , lipopolysaccharide , contractility , metabolite , prostaglandin
Aim: To evaluate the effect of progesterone on interleukin (IL)‐6, prostaglandin (PG) E 2 and nitric oxide (NO) metabolite (NOx) production and contractile activity by NO in pregnant mice treated with lipopolysaccharide (LPS). Methods: Pregnant C57BL mice on day 14 of gestation were killed 6 h after i.p. injection of LPS (400 μg/kg) or vehicle. Progesterone (2 mg) was subcutaneously injected 2 h before LPS treatment. Uterine rings were equilibrated in Krebs‐Henseleit solution (37°C) bubbled with 20% O 2 and 5% CO 2 (pH 7.4) for sampling and isometric tension recording. IL‐6, PGE 2 and NOx productions were measured from the bathing solution. Changes in spontaneous contractile activity in response to cumulative concentrations of l ‐arginine, diethylamine/nitric oxide (DEA/NO, the NO donor), and 8‐bromo‐cGMP (8‐br‐cGMP) were compared. Integral contractile activity over 10 min after each concentration was calculated and expressed as percentage change from basal activity. Statistical analyses were performed using one‐way anova followed by Dunnett's test (significance was defined as P < 0.05). Results: Interleukin‐6 (34.7 ± 6.0 pg/g tissue), PGE 2 (66.8 ± 6.7 pg/g tissue) and NOx (51.0 ± 5.4 pmol/2 mL/g wet tissue) production were significantly stimulated by LPS treatment (138.2 ± 23.2, 147.0 ± 29.0, 98.6 ± 16.2, respectively; P < 0.05). l ‐arginine, DEA/NO and 8‐br‐cGMP concentration‐dependently inhibited spontaneous contractions in uterine rings both in LPS‐treated and ‐untreated animals. Treatment with LPS significantly attenuated the maximal inhibition induced by l ‐arginine, DEA/NO and 8‐br‐cGMP in uterine rings from pregnant mice. Progesterone significantly decreased the levels of IL‐6 production (74.9 ± 12.1, P < 0.05), but not PGE 2 and NOx production, and contractile responses by l ‐arginine, DEA/NO and 8‐br‐cGMP. Conclusions: The administration of LPS is associated with increases in IL‐6, PGE 2 and NO, and these increases may or may not have a role to play in LPS‐induced preterm labor. Progesterone reduced the LPS‐induced increase in IL‐6 production and this may be one of the ways that progesterone reduces the risk of preterm labor.