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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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Concentration-dependent effects of lindane on sustained inhibition of Lucifer yellow dye transfer. Lucifer yellow dye transfer between myometrial cells was inhibited in a concentration-dependent manner 24 h after initiating 1-h or 24-h treatments with 100 μM lindane (ANOVA, p ≤ 0.0001. Mean values ± S.E.M. are shown (n = 5–8 culture dishes; 7–22 cells were injected per dish). Vertical bars with different letters have means that are significantly different from each other in pair-wise comparisons (Student-Newman-Keuls, p ≤ 0.05).
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Figure 8: Concentration-dependent effects of lindane on sustained inhibition of Lucifer yellow dye transfer. Lucifer yellow dye transfer between myometrial cells was inhibited in a concentration-dependent manner 24 h after initiating 1-h or 24-h treatments with 100 μM lindane (ANOVA, p ≤ 0.0001. Mean values ± S.E.M. are shown (n = 5–8 culture dishes; 7–22 cells were injected per dish). Vertical bars with different letters have means that are significantly different from each other in pair-wise comparisons (Student-Newman-Keuls, p ≤ 0.05).

Mentions: The effect of exposure duration on lindane-induced inhibition of Lucifer yellow dye transfer was examined further in an experiment that included concentrations ranging from 0.01 μM to 100 μM lindane. As shown in Figure 8, lindane significantly inhibited dye transfer in similar concentration-dependent manners 24 h after a 1-h exposure or after a 24-h continuous exposure (ANOVA, p ≤ 0.0001). Regardless of whether exposure was for 1 h or 24 h, 0.01 μM lindane had no significant effect on dye transfer 24 h after initiating exposure. In contrast, 0.1 μM lindane significantly depressed dye transfer to 81.1 ± 3.1% and 81.6 ± 3.1% 24 h after initiating exposure for 1 h or 24 h, respectively, compared with solvent controls (Fig. 8, p ≤ 0.05). Dye transfer was depressed further in cultures exposed to 1, 10 or 100 μM lindane compared with controls and 0.01 μM lindane (p ≤ 0.05), although a concentration-dependent response was not observed in this concentration range (Fig. 8). These results show that brief (1 h) and extended (24 h) exposures to lindane inhibited myometrial gap junction communication to similar extents, as measured by Lucifer yellow dye transfer, and that a low concentration of lindane (0.1 μM) inhibited myometrial gap junction communication in a sustained manner. There was not a significant difference between the percentage of cells excluding trypan blue in the solvent (DMSO) control and the 100 μM lindane treatment group 24 h after exposure (data not shown), indicating an absence of overt cytotoxicity.


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

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

Concentration-dependent effects of lindane on sustained inhibition of Lucifer yellow dye transfer. Lucifer yellow dye transfer between myometrial cells was inhibited in a concentration-dependent manner 24 h after initiating 1-h or 24-h treatments with 100 μM lindane (ANOVA, p ≤ 0.0001. Mean values ± S.E.M. are shown (n = 5–8 culture dishes; 7–22 cells were injected per dish). Vertical bars with different letters have means that are significantly different from each other in pair-wise comparisons (Student-Newman-Keuls, p ≤ 0.05).
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Related In: Results  -  Collection

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Figure 8: Concentration-dependent effects of lindane on sustained inhibition of Lucifer yellow dye transfer. Lucifer yellow dye transfer between myometrial cells was inhibited in a concentration-dependent manner 24 h after initiating 1-h or 24-h treatments with 100 μM lindane (ANOVA, p ≤ 0.0001. Mean values ± S.E.M. are shown (n = 5–8 culture dishes; 7–22 cells were injected per dish). Vertical bars with different letters have means that are significantly different from each other in pair-wise comparisons (Student-Newman-Keuls, p ≤ 0.05).
Mentions: The effect of exposure duration on lindane-induced inhibition of Lucifer yellow dye transfer was examined further in an experiment that included concentrations ranging from 0.01 μM to 100 μM lindane. As shown in Figure 8, lindane significantly inhibited dye transfer in similar concentration-dependent manners 24 h after a 1-h exposure or after a 24-h continuous exposure (ANOVA, p ≤ 0.0001). Regardless of whether exposure was for 1 h or 24 h, 0.01 μM lindane had no significant effect on dye transfer 24 h after initiating exposure. In contrast, 0.1 μM lindane significantly depressed dye transfer to 81.1 ± 3.1% and 81.6 ± 3.1% 24 h after initiating exposure for 1 h or 24 h, respectively, compared with solvent controls (Fig. 8, p ≤ 0.05). Dye transfer was depressed further in cultures exposed to 1, 10 or 100 μM lindane compared with controls and 0.01 μM lindane (p ≤ 0.05), although a concentration-dependent response was not observed in this concentration range (Fig. 8). These results show that brief (1 h) and extended (24 h) exposures to lindane inhibited myometrial gap junction communication to similar extents, as measured by Lucifer yellow dye transfer, and that a low concentration of lindane (0.1 μM) inhibited myometrial gap junction communication in a sustained manner. There was not a significant difference between the percentage of cells excluding trypan blue in the solvent (DMSO) control and the 100 μM lindane treatment group 24 h after exposure (data not shown), indicating an absence of overt cytotoxicity.

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