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Article
Nature Medicine  10, 1074 - 1080 (2004)
Published online: 19 September 2004; | doi:10.1038/nm1104


There is a Corrigendum (December 2004) associated with this Article.

Aberrant cannabinoid signaling impairs oviductal transport of embryos

Haibin Wang1, Yong Guo1, Dingzhi Wang2, Philip J Kingsley3, Lawrence J Marnett3, Sanjoy K Das1, 4, Raymond N DuBois2, 4, 5 & Sudhansu K Dey1, 5, 6

1  Department of Pediatrics, Division of Reproductive and Developmental Biology, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, Tennessee 37232, USA.

2  Department of Medicine, Division of Reproductive and Developmental Biology, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, Tennessee 37232, USA.

3  Department of Biochemistry, Institute of Chemical Biology, Division of Reproductive and Developmental Biology, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, Tennessee 37232, USA.

4  Department of Cancer Biology, Division of Reproductive and Developmental Biology, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, Tennessee 37232, USA.

5  Department of Pharmacology, Division of Reproductive and Developmental Biology, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, Tennessee 37232, USA.

6  Departments of Cell and Developmental Biology, Division of Reproductive and Developmental Biology, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, Tennessee 37232, USA.

Correspondence should be addressed to Sudhansu K Dey sk.dey@vanderbilt.edu
Ectopic pregnancy is a major reproductive health issue. Although other underlying causes remain largely unknown, one cause of ectopic pregnancy is embryo retention in the fallopian tube. Here we show that genetic or pharmacologic silencing of cannabinoid receptor CB1 causes retention of a large number of embryos in the mouse oviduct, eventually leading to pregnancy failure. This is reversed by isoproterenol, a beta-adrenergic receptor agonist. Impaired oviductal embryo transport is also observed in wild-type mice treated with methanandamide. Collectively, the results suggest that aberrant cannabinoid signaling impedes coordinated oviductal smooth muscle contraction and relaxation crucial to normal oviductal embryo transport. Colocalization of CB1 and beta2-adrenergic receptors in the oviduct muscularis implies that a basal endocannabinoid tone in collaboration with adrenergic receptors coordinates oviductal motility for normal journey of embryos into the uterus. Besides uncovering a new regulatory mechanism, this study could be clinically relevant to ectopic pregnancy.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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