Loch-Caruso Rita K, Criswell Kay A, Grindatti Carmen M, Brant Kelly A
Toxicology Program, Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA.
Reprod Biol Endocrinol. 2003 Oct 3;1:62. doi: 10.1186/1477-7827-1-62.
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.
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.
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.
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.
缝隙连接的大小和丰度在分娩时增加，形成一个细胞间通讯网络，使子宫能够产生分娩胎儿所需的有力、协调的收缩。林丹是一种用于人类和兽医治疗疥疮和虱子以及农业应用的杀虫剂，它在体外抑制子宫收缩，抑制子宫肌层缝隙连接，并且与大鼠妊娠期延长有关。本研究的目的是调查短期接触林丹是否会引起大鼠子宫收缩活动和子宫肌层缝隙连接细胞间通讯的持续抑制。
为了检查对子宫收缩的影响，从妊娠晚期（第20天）大鼠分离的子宫纵条在肌肉浴中暴露于林丹，并在暴露于林丹期间和之后监测自发相性收缩的变化。利用培养的子宫肌层细胞间荧光素黄染料转移来监测缝隙连接细胞间通讯。
在1小时的暴露期间，10微摩尔/升和100微摩尔/升的林丹降低了子宫收缩的峰值力和频率，但1微摩尔/升的林丹没有。去除暴露缓冲液后，暴露于100微摩尔/升林丹的子宫条收缩力仍显著降低，在林丹暴露停止后5小时恢复到低于基础水平的50%。在培养的子宫肌层肌细胞中，在短至10分钟、低至0.1微摩尔/升林丹暴露24小时后，观察到荧光素黄染料转移受到显著的持续抑制。
体外短期接触林丹对分娩所需的子宫肌层功能有长期影响，抑制妊娠晚期大鼠子宫的自发相性收缩和子宫肌层细胞培养中的缝隙连接细胞间通讯。
