Aberrant cannabinoid signaling impairs oviductal transport of embryos.
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.
Wang
Haibin
H
Department of Pediatrics, Division of Reproductive and Developmental Biology, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, Tennessee 37232, USA.
Guo
Yong
Y
Wang
Dingzhi
D
Kingsley
Philip J
PJ
Marnett
Lawrence J
LJ
Das
Sanjoy K
SK
DuBois
Raymond N
RN
Dey
Sudhansu K
SK
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids; D015139:Blotting, Southern; D004624:Embryo Transfer; D005187:Fallopian Tubes / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology*; D051379:Mice; D008957:Models, Genetic; D009119:Muscle Contraction / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism*; D010066:Ovum Transport / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D001095:Arachidonic Acids; D043884:Receptor, Cannabinoid, CB1; C088155:methanandamide; D007545:Isoproterenol; D009638:Norepinephrine