Aberrant cannabinoid signaling impairs oviductal transport of embryos

Haibin Wang, Yong Guo, Dingzhi Wang, Philip J. Kingsley, Lawrence J. Marnett, Sanjoy K. Das, Raymond N. DuBois, Sudhansu K. Dey

Research output: Contribution to journalArticle

156 Scopus citations

Abstract

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 β-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 β2-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.

Original languageEnglish (US)
Pages (from-to)1074-1080
Number of pages7
JournalNature Medicine
Volume10
Issue number10
DOIs
StatePublished - Oct 1 2004

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Wang, H., Guo, Y., Wang, D., Kingsley, P. J., Marnett, L. J., Das, S. K., DuBois, R. N., & Dey, S. K. (2004). Aberrant cannabinoid signaling impairs oviductal transport of embryos. Nature Medicine, 10(10), 1074-1080. https://doi.org/10.1038/nm1104