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


CONCLUSIONS
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.
Toxicology Program, Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA. rlc@umich.edu
Rita K
RK
Loch-Caruso
Kay A
KA
Criswell
Carmen M
CM
Grindatti
Kelly A
KA
Brant
D000818:Animals; D002021:Buffers; D002478:Cells, Cultured; D005260:Female; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000378:metabolism; D009215:Myometrium / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology
D002021:Buffers; D007546:Isoquinolines; D001556:Hexachlorocyclohexane; C017475:lucifer yellow