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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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Representative polygraph tracings of longitudinal muscle strips. Uterine strips were isolated from uteri of gestation day 20 rats and exposed in muscle baths to 0.2% DMSO (solvent control) or 1, 10 or 100 μM lindane for 1 h. After exposure, the strips were rinsed 3 times and monitored in fresh physiological salt solution without test chemicals for an additional 5 h. A) Five minutes prior to exposure and 30 min after initiating a 1-h exposure (arrows mark addition of test chemical). B) 4.5 hours after rinsing (10 min shown).
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Figure 1: Representative polygraph tracings of longitudinal muscle strips. Uterine strips were isolated from uteri of gestation day 20 rats and exposed in muscle baths to 0.2% DMSO (solvent control) or 1, 10 or 100 μM lindane for 1 h. After exposure, the strips were rinsed 3 times and monitored in fresh physiological salt solution without test chemicals for an additional 5 h. A) Five minutes prior to exposure and 30 min after initiating a 1-h exposure (arrows mark addition of test chemical). B) 4.5 hours after rinsing (10 min shown).

Mentions: Figure 1A shows representative polygraph tracings of muscle contractions of gestation day (GD) 20 uterine strips before and during exposure to 0.2% DMSO (solvent control) or 1, 10 or 100 μM lindane. These concentrations of lindane were selected based upon previous reports that this was an effective concentration range for inhibition of contractions in GD10 uterine strips [7] and for inhibition of gap junction intercellular communication between myometrial myocytes in culture [8,30]. As seen in Figure 1A, the addition of 10 μM or 100 μM lindane, but not 1 μM lindane or DMSO (solvent control), rapidly decreased the peak amplitude (force) of spontaneous phasic contractions. Inherent differences between uterine strips in basal contractility were not uncommon, as seen in the examples in Figure 1. Consequently, to quantify changes in contractions, the data were expressed as percent basal contraction force for individual strips prior to summarization, as described in Methods.


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

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

Representative polygraph tracings of longitudinal muscle strips. Uterine strips were isolated from uteri of gestation day 20 rats and exposed in muscle baths to 0.2% DMSO (solvent control) or 1, 10 or 100 μM lindane for 1 h. After exposure, the strips were rinsed 3 times and monitored in fresh physiological salt solution without test chemicals for an additional 5 h. A) Five minutes prior to exposure and 30 min after initiating a 1-h exposure (arrows mark addition of test chemical). B) 4.5 hours after rinsing (10 min shown).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Representative polygraph tracings of longitudinal muscle strips. Uterine strips were isolated from uteri of gestation day 20 rats and exposed in muscle baths to 0.2% DMSO (solvent control) or 1, 10 or 100 μM lindane for 1 h. After exposure, the strips were rinsed 3 times and monitored in fresh physiological salt solution without test chemicals for an additional 5 h. A) Five minutes prior to exposure and 30 min after initiating a 1-h exposure (arrows mark addition of test chemical). B) 4.5 hours after rinsing (10 min shown).
Mentions: Figure 1A shows representative polygraph tracings of muscle contractions of gestation day (GD) 20 uterine strips before and during exposure to 0.2% DMSO (solvent control) or 1, 10 or 100 μM lindane. These concentrations of lindane were selected based upon previous reports that this was an effective concentration range for inhibition of contractions in GD10 uterine strips [7] and for inhibition of gap junction intercellular communication between myometrial myocytes in culture [8,30]. As seen in Figure 1A, the addition of 10 μM or 100 μM lindane, but not 1 μM lindane or DMSO (solvent control), rapidly decreased the peak amplitude (force) of spontaneous phasic contractions. Inherent differences between uterine strips in basal contractility were not uncommon, as seen in the examples in Figure 1. Consequently, to quantify changes in contractions, the data were expressed as percent basal contraction force for individual strips prior to summarization, as described in Methods.

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