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Sustained inhibition of rat myometrial gap junctions and contractions by lindane.

Loch-Caruso RK, Criswell KA, Grindatti CM, Brant KA - Reprod. Biol. Endocrinol. (2003)

Bottom Line: Gap junctions increase in size and abundance coincident with parturition, forming an intercellular communication network that permits the uterus to develop the forceful, coordinated contractions necessary for delivery of the fetus.To examine effects on uterine contraction, longitudinal uterine strips isolated from late gestation (day 20) rats were exposed to lindane in muscle baths and monitored for changes in spontaneous phasic contractions during and after exposure to lindane.After removal of the exposure buffer, contraction force remained significantly depressed in uterine strips exposed to 100 micro M lindane, returning to less than 50% basal levels 5 h after cessation of lindane exposure.

View Article: PubMed Central - HTML - PubMed

Affiliation: Toxicology Program, Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA. rlc@umich.edu

ABSTRACT

Background: Gap junctions increase in size and abundance coincident with parturition, forming an intercellular communication network that permits the uterus to develop the forceful, coordinated contractions necessary for delivery of the fetus. Lindane, a pesticide used in the human and veterinary treatment of scabies and lice as well as in agricultural applications, inhibits uterine contractions in vitro, inhibits myometrial gap junctions, and has been associated with prolonged gestation length in rats. The aim of the present study was to investigate whether brief exposures to lindane would elicit sustained inhibition of rat uterine contractile activity and myometrial gap junction intercellular communication.

Methods: To examine effects on uterine contraction, longitudinal uterine strips isolated from late gestation (day 20) rats were exposed to lindane in muscle baths and monitored for changes in spontaneous phasic contractions during and after exposure to lindane. Lucifer yellow dye transfer between myometrial cells in culture was used to monitor gap junction intercellular communication.

Results: During a 1-h exposure, 10 micro M and 100 micro M lindane decreased peak force and frequency of uterine contraction but 1 micro M lindane did not. After removal of the exposure buffer, contraction force remained significantly depressed in uterine strips exposed to 100 micro M lindane, returning to less than 50% basal levels 5 h after cessation of lindane exposure. In cultured myometrial myocytes, significant sustained inhibition of Lucifer yellow dye transfer was observed 24 h after lindane exposures as brief as 10 min and as low as 0.1 micro M lindane.

Conclusion: Brief in vitro exposures to lindane have long-term effects on myometrial functions that are necessary for parturition, inhibiting spontaneous phasic contractions in late gestation rat uterus and gap junction intercellular communication in myometrial cell cultures.

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Time- and concentration-related effects of lindane on uterine contraction force (A) and frequency (B). Uterine strips were exposed to lindane (1, 10 or 100 μM) as described in Figure 1. The average peak force of contraction and the average frequency of contraction were calculated relative to basal (pretreatment) values, as described in Methods, over 30-min intervals of a 1-h exposure. Changes in contraction force and frequency were analyzed by separate repeated measures analysis of variance (ANOVA) for concentration, exposure duration, and interaction effects, with repeated measures on exposure duration. Lindane decreased uterine contraction frequency and force in concentration-dependent and time-dependent manners, with a significant interaction between concentration and exposure duration (ANOVA, p ≤ 0.001). Vertical bars with different letters have means that are significantly different from each other in pairwise comparisons (Student-Newman-Keuls, p ≤ 0.05). Values shown are mean ± SEM of 7 uterine strips. Error bars not visible are too small to be displayed graphically.
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Figure 2: Time- and concentration-related effects of lindane on uterine contraction force (A) and frequency (B). Uterine strips were exposed to lindane (1, 10 or 100 μM) as described in Figure 1. The average peak force of contraction and the average frequency of contraction were calculated relative to basal (pretreatment) values, as described in Methods, over 30-min intervals of a 1-h exposure. Changes in contraction force and frequency were analyzed by separate repeated measures analysis of variance (ANOVA) for concentration, exposure duration, and interaction effects, with repeated measures on exposure duration. Lindane decreased uterine contraction frequency and force in concentration-dependent and time-dependent manners, with a significant interaction between concentration and exposure duration (ANOVA, p ≤ 0.001). Vertical bars with different letters have means that are significantly different from each other in pairwise comparisons (Student-Newman-Keuls, p ≤ 0.05). Values shown are mean ± SEM of 7 uterine strips. Error bars not visible are too small to be displayed graphically.

Mentions: Uterine strips treated with solvent (controls) or 1 μM lindane showed no significant differences in peak contraction force or frequency during the 1-h exposure (Fig. 2). In contrast, the average peak force and frequency of contraction decreased in concentration-dependent (ANOVA, p ≤ 0.001) and time-dependent (ANOVA, p ≤ 0.001) manners during 1-h exposures to 10 μM or 100 μM lindane (Fig. 2). During the first half hour of exposure, the average peak force of contraction was depressed by 100 μM lindane to 60.8 ± 4.0 %, a significant decrease in comparison with the 100 μM lindane group basal (pretreatment) and the time-matched 1 μM lindane treatment group (95.1 ± 1.6 %) (Fig. 2A, p ≤ 0.05), but not compared with time-matched solvent (DMSO) controls (87.6 ± 9.7 %). During the 0.5–1 h exposure period, the average peak force of contraction was further depressed by 10 μM to 11.7 ± 5.5% and by 100 μM lindane to 0.0 ± 0.0 %, significantly different from the preceding 0–0.5 h exposure period for each respective lindane treatment, time-matched solvent (DMSO) controls (94 ± 10.3%), and the time-matched 1 μM lindane treatment group (97.8 ± 2.7 %) (Fig. 2A, p ≤ 0.05).


Sustained inhibition of rat myometrial gap junctions and contractions by lindane.

Loch-Caruso RK, Criswell KA, Grindatti CM, Brant KA - Reprod. Biol. Endocrinol. (2003)

Time- and concentration-related effects of lindane on uterine contraction force (A) and frequency (B). Uterine strips were exposed to lindane (1, 10 or 100 μM) as described in Figure 1. The average peak force of contraction and the average frequency of contraction were calculated relative to basal (pretreatment) values, as described in Methods, over 30-min intervals of a 1-h exposure. Changes in contraction force and frequency were analyzed by separate repeated measures analysis of variance (ANOVA) for concentration, exposure duration, and interaction effects, with repeated measures on exposure duration. Lindane decreased uterine contraction frequency and force in concentration-dependent and time-dependent manners, with a significant interaction between concentration and exposure duration (ANOVA, p ≤ 0.001). Vertical bars with different letters have means that are significantly different from each other in pairwise comparisons (Student-Newman-Keuls, p ≤ 0.05). Values shown are mean ± SEM of 7 uterine strips. Error bars not visible are too small to be displayed graphically.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC222921&req=5

Figure 2: Time- and concentration-related effects of lindane on uterine contraction force (A) and frequency (B). Uterine strips were exposed to lindane (1, 10 or 100 μM) as described in Figure 1. The average peak force of contraction and the average frequency of contraction were calculated relative to basal (pretreatment) values, as described in Methods, over 30-min intervals of a 1-h exposure. Changes in contraction force and frequency were analyzed by separate repeated measures analysis of variance (ANOVA) for concentration, exposure duration, and interaction effects, with repeated measures on exposure duration. Lindane decreased uterine contraction frequency and force in concentration-dependent and time-dependent manners, with a significant interaction between concentration and exposure duration (ANOVA, p ≤ 0.001). Vertical bars with different letters have means that are significantly different from each other in pairwise comparisons (Student-Newman-Keuls, p ≤ 0.05). Values shown are mean ± SEM of 7 uterine strips. Error bars not visible are too small to be displayed graphically.
Mentions: Uterine strips treated with solvent (controls) or 1 μM lindane showed no significant differences in peak contraction force or frequency during the 1-h exposure (Fig. 2). In contrast, the average peak force and frequency of contraction decreased in concentration-dependent (ANOVA, p ≤ 0.001) and time-dependent (ANOVA, p ≤ 0.001) manners during 1-h exposures to 10 μM or 100 μM lindane (Fig. 2). During the first half hour of exposure, the average peak force of contraction was depressed by 100 μM lindane to 60.8 ± 4.0 %, a significant decrease in comparison with the 100 μM lindane group basal (pretreatment) and the time-matched 1 μM lindane treatment group (95.1 ± 1.6 %) (Fig. 2A, p ≤ 0.05), but not compared with time-matched solvent (DMSO) controls (87.6 ± 9.7 %). During the 0.5–1 h exposure period, the average peak force of contraction was further depressed by 10 μM to 11.7 ± 5.5% and by 100 μM lindane to 0.0 ± 0.0 %, significantly different from the preceding 0–0.5 h exposure period for each respective lindane treatment, time-matched solvent (DMSO) controls (94 ± 10.3%), and the time-matched 1 μM lindane treatment group (97.8 ± 2.7 %) (Fig. 2A, p ≤ 0.05).

Bottom Line: Gap junctions increase in size and abundance coincident with parturition, forming an intercellular communication network that permits the uterus to develop the forceful, coordinated contractions necessary for delivery of the fetus.To examine effects on uterine contraction, longitudinal uterine strips isolated from late gestation (day 20) rats were exposed to lindane in muscle baths and monitored for changes in spontaneous phasic contractions during and after exposure to lindane.After removal of the exposure buffer, contraction force remained significantly depressed in uterine strips exposed to 100 micro M lindane, returning to less than 50% basal levels 5 h after cessation of lindane exposure.

View Article: PubMed Central - HTML - PubMed

Affiliation: Toxicology Program, Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA. rlc@umich.edu

ABSTRACT

Background: Gap junctions increase in size and abundance coincident with parturition, forming an intercellular communication network that permits the uterus to develop the forceful, coordinated contractions necessary for delivery of the fetus. Lindane, a pesticide used in the human and veterinary treatment of scabies and lice as well as in agricultural applications, inhibits uterine contractions in vitro, inhibits myometrial gap junctions, and has been associated with prolonged gestation length in rats. The aim of the present study was to investigate whether brief exposures to lindane would elicit sustained inhibition of rat uterine contractile activity and myometrial gap junction intercellular communication.

Methods: To examine effects on uterine contraction, longitudinal uterine strips isolated from late gestation (day 20) rats were exposed to lindane in muscle baths and monitored for changes in spontaneous phasic contractions during and after exposure to lindane. Lucifer yellow dye transfer between myometrial cells in culture was used to monitor gap junction intercellular communication.

Results: During a 1-h exposure, 10 micro M and 100 micro M lindane decreased peak force and frequency of uterine contraction but 1 micro M lindane did not. After removal of the exposure buffer, contraction force remained significantly depressed in uterine strips exposed to 100 micro M lindane, returning to less than 50% basal levels 5 h after cessation of lindane exposure. In cultured myometrial myocytes, significant sustained inhibition of Lucifer yellow dye transfer was observed 24 h after lindane exposures as brief as 10 min and as low as 0.1 micro M lindane.

Conclusion: Brief in vitro exposures to lindane have long-term effects on myometrial functions that are necessary for parturition, inhibiting spontaneous phasic contractions in late gestation rat uterus and gap junction intercellular communication in myometrial cell cultures.

Show MeSH
Related in: MedlinePlus