Chlamydia Infection Causes Loss of Pacemaker Cells and Inhibits Oocyte Transport in the Mouse Oviduct
Chlamydia Infection Causes Loss of Pacemaker Cells and Inhibits Oocyte Transport in the Mouse Oviduct
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DOI：
10.1095/biolreprod.108.073833
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发表时间：
2009-04-01
影响因子：
3.6
通讯作者：
Ward, Sean M.
中科院分区：
文献类型：
--
作者：
Dixon, Rose Ellen;Hwang, Sung Jin;Ward, Sean M.
沙眼衣原体是一种常见的性传播细菌感染，导致美国每年的医疗保健费用超过 20 亿美元。衣原体感染会损害输卵管，导致宫外孕和输卵管因素不孕，但输卵管功能缺陷的原因却知之甚少。我们研究了输卵管收缩在卵子运输中的作用，发现潜在的电起搏器活动负责输卵管运动和卵子运输。特殊的起搏细胞，称为卡哈尔输卵管间质细胞 (ICC-OVI)，负责起搏器活动。 ICC-OVI 标记有 KIT 蛋白抗体，形成与输卵管整个长度上的平滑肌细胞相关的致密网络。使用 KIT 中和抗体选择性去除 ICC-OVI 会导致电节律性丧失和输卵管推进性收缩丧失。我们测试了感染是否会对 ICC-OVI 产生不利影响。感染鼠衣原体的小鼠表现出输卵管、输卵管扩张和自发收缩活动丧失。形态学检查显示 ICC-OVI 网络中断，电生理记录显示内在起搏器活性丧失，但基底平滑肌膜电位没有变化。衣原体感染还与白细胞中 NOS2 (iNOS) 和 PTGS2 (COX II) 的上调有关。 ICC-OVI 和起搏器活性的丧失会导致输卵管假性梗阻和卵母细胞推进收缩的丧失。这加上输卵管分泌物的滞留，可能会导致输卵管因素不孕的发生。
Chlamydia trachomatis is a common sexually transmitted bacterial infection that results in health care costs in the United States that exceed $2 billion per year. Chlamydia infections cause damage to the oviducts, resulting in ectopic pregnancy and tubal factor infertility, but the reasons for defective oviduct function are poorly understood. We have investigated the role of oviduct contractions in egg transport and found that underlying electrical pacemaker activity is responsible for oviduct motility and egg transport. Specialized pacemaker cells, referred to as oviduct interstitial cells of Cajal (ICC-OVI), are responsible for pacemaker activity. The ICC-OVI, labeled with antibodies to KIT protein, form a dense network associated with the smooth muscle cells along the entire length of the oviduct. Selective removal of ICC-OVI with KIT-neutralizing antibody resulted in loss of electrical rhythmicity and loss of propulsive contractions of the oviduct. We tested whether infection might adversely affect the ICC-OVI. Mice infected with Chlamydia muridarum displayed dilation of oviducts, pyosalpinx, and loss of spontaneous contractile activity. Morphological inspection showed disruption of ICC-OVI networks, and electrophysiological recordings showed loss of intrinsic pacemaker activity without change in basal smooth muscle membrane potential. Chlamydia infection also was associated with upregulation of NOS2 (iNOS) and PTGS2 (COX II) in leukocytes. Loss of ICC-OVI and pacemaker activity causes oviduct pseudo-obstruction and loss of propulsive contractions for oocytes. This, accompanied by retention of oviduct secretions, may contribute to the development of tubal factor infertility.