Chlamydia infection causes loss of pacemaker cells and inhibits oocyte transport in the mouse oviduct.
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.
Dixon
Rose Ellen
RE
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada.
Hwang
Sung Jin
SJ
Hennig
Grant W
GW
Ramsey
Kyle H
KH
Schripsema
Justin H
JH
Sanders
Kenton M
KM
Ward
Sean M
SM
D000818:Animals; D000831:Animals, Newborn; D001683:Biological Clocks / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002690:Chlamydia Infections / Q000473:pathology / Q000503:physiopathology*; D023502:Chlamydia muridarum / Q000502:physiology; D002923:Cilia / Q000473:pathology; D004594:Electrophysiology; D005187:Fallopian Tubes / Q000378:metabolism / Q000382:microbiology / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009119:Muscle Contraction / Q000502:physiology; D009865:Oocytes / Q000502:physiology*; D009924:Organ Culture Techniques