N-acylphosphatidylethanolamine-hydrolyzing phospholipase D is an important determinant of uterine anandamide levels during implantation.
Implantation requires reciprocal interaction between blastocysts and a receptive uterus. In mice, one important player in this dialogue involves endocannabinoid signaling via cannabinoid receptor CB1. Anandamide is an endogenous cannabinoid ligand, and its levels are spatiotemporally regulated in the uterus during early pregnancy, showing lower levels in the receptive uterus and at the implantation site. However, the mechanism by which differential uterine anandamide gradients are established under different pregnancy status is not clearly understood. Using multiple approaches, we show here that uterine anandamide levels conducive to implantation are primarily regulated by spatiotemporal expression of Nape-Pld, the gene encoding N-acylphosphatidylethanolamine-hydrolyzing phospholipase D that generates anandamide. The expression is well correlated with its activity and anandamide levels. This study is clinically relevant, since elevated anandamide levels in peripheral circulation are associated with spontaneous pregnancy failure in women.
Guo
Yong
Y
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Wang
Haibin
H
Okamoto
Yasuo
Y
Ueda
Natsuo
N
Kingsley
Philip J
PJ
Marnett
Lawrence J
LJ
Schmid
Harald H O
HH
Das
Sanjoy K
SK
Dey
Sudhansu K
SK
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers; D015536:Down-Regulation / Q000502:physiology; D010064:Embryo Implantation / Q000502:physiology*; D063388:Endocannabinoids; D004967:Estrogens / Q000502:physiology; D005260:Female; D006868:Hydrolysis; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D010727:Phosphoric Diester Hydrolases / Q000502:physiology*; D053284:Polyunsaturated Alkamides; D011247:Pregnancy; D011374:Progesterone / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014599:Uterus / Q000201:enzymology / Q000378:metabolism*
D001095:Arachidonic Acids; D017931:DNA Primers; D063388:Endocannabinoids; D004967:Estrogens; D053284:Polyunsaturated Alkamides; D011374:Progesterone; C431824:N-acylphosphatidylethanolamine-hydrolyzing phosphodiesterase; D010727:Phosphoric Diester Hydrolases; C078814:anandamide