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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-dependent effects on Lucifer yellow dye transfer after exposure to lindane. A 1-h treatment of rat myometrial cells with 100 μM lindane initially abolished Lucifer yellow dye transfer (zero hour time-point), and then after removal of lindane exposure buffer and rinsing, this inhibition first reversed before redeveloping (ANOVA, p ≤ 0.0001). Mean values ± S.E.M. are shown (n = 3–5 culture dishes; 8–14 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). Cultures exposed to solvent (DMSO) alone for 1 h were assessed 24 h after rinsing, and were found to transfer dye to 98.4 ± 1.7% of neighboring cells (data not shown on graph).
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Figure 6: Time-dependent effects on Lucifer yellow dye transfer after exposure to lindane. A 1-h treatment of rat myometrial cells with 100 μM lindane initially abolished Lucifer yellow dye transfer (zero hour time-point), and then after removal of lindane exposure buffer and rinsing, this inhibition first reversed before redeveloping (ANOVA, p ≤ 0.0001). Mean values ± S.E.M. are shown (n = 3–5 culture dishes; 8–14 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). Cultures exposed to solvent (DMSO) alone for 1 h were assessed 24 h after rinsing, and were found to transfer dye to 98.4 ± 1.7% of neighboring cells (data not shown on graph).

Mentions: At the end of a 1-h exposure to 100 μM lindane and before rinsing, Lucifer yellow dye transfer was abolished between myometrial cells in culture (Fig. 6, zero time point), as expected based on previous reports [8,30]. After rinsing, intercellular transfer Lucifer yellow dye initially improved before declining again (Fig. 6, ANOVA, p ≤ 0.0001). Within 30 min after rinsing, dye transfer had recovered to 99.5 ± 0.5% (p ≤ 0.05 compared with zero time point), a level similar to that observed in solvent control cultures assessed 24 h after a 1-h exposure (98.4 ± 1.7%, data not shown on graph). However, dye transfer declined in the lindane-exposed cell cultures in a time-dependent manner to 81.6 ± 1.8% after 1 h (p ≤ 0.05 compared with 0.5 h after rinsing), and reached a minimum by 4 h that persisted for 24 h (p ≤ 0.05 compared with 0, 0.5, 1 and 2 h after rinsing; Fig. 6). This pattern of dye transfer indicates that lindane-induced inhibition of myometrial gap junction communication, as measured by Lucifer yellow dye transfer, was initially rapidly reversible, but that a secondary and sustained inhibition of dye transfer developed in the absence of further exposure to lindane after a brief delay.


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-dependent effects on Lucifer yellow dye transfer after exposure to lindane. A 1-h treatment of rat myometrial cells with 100 μM lindane initially abolished Lucifer yellow dye transfer (zero hour time-point), and then after removal of lindane exposure buffer and rinsing, this inhibition first reversed before redeveloping (ANOVA, p ≤ 0.0001). Mean values ± S.E.M. are shown (n = 3–5 culture dishes; 8–14 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). Cultures exposed to solvent (DMSO) alone for 1 h were assessed 24 h after rinsing, and were found to transfer dye to 98.4 ± 1.7% of neighboring cells (data not shown on graph).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC222921&req=5

Figure 6: Time-dependent effects on Lucifer yellow dye transfer after exposure to lindane. A 1-h treatment of rat myometrial cells with 100 μM lindane initially abolished Lucifer yellow dye transfer (zero hour time-point), and then after removal of lindane exposure buffer and rinsing, this inhibition first reversed before redeveloping (ANOVA, p ≤ 0.0001). Mean values ± S.E.M. are shown (n = 3–5 culture dishes; 8–14 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). Cultures exposed to solvent (DMSO) alone for 1 h were assessed 24 h after rinsing, and were found to transfer dye to 98.4 ± 1.7% of neighboring cells (data not shown on graph).
Mentions: At the end of a 1-h exposure to 100 μM lindane and before rinsing, Lucifer yellow dye transfer was abolished between myometrial cells in culture (Fig. 6, zero time point), as expected based on previous reports [8,30]. After rinsing, intercellular transfer Lucifer yellow dye initially improved before declining again (Fig. 6, ANOVA, p ≤ 0.0001). Within 30 min after rinsing, dye transfer had recovered to 99.5 ± 0.5% (p ≤ 0.05 compared with zero time point), a level similar to that observed in solvent control cultures assessed 24 h after a 1-h exposure (98.4 ± 1.7%, data not shown on graph). However, dye transfer declined in the lindane-exposed cell cultures in a time-dependent manner to 81.6 ± 1.8% after 1 h (p ≤ 0.05 compared with 0.5 h after rinsing), and reached a minimum by 4 h that persisted for 24 h (p ≤ 0.05 compared with 0, 0.5, 1 and 2 h after rinsing; Fig. 6). This pattern of dye transfer indicates that lindane-induced inhibition of myometrial gap junction communication, as measured by Lucifer yellow dye transfer, was initially rapidly reversible, but that a secondary and sustained inhibition of dye transfer developed in the absence of further exposure to lindane after a brief delay.

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