Low fatty acid amide hydrolase and high anandamide levels are associated with failure to achieve an ongoing pregnancy after IVF and embryo transfer.
Human reproduction is a rather inefficient process, yet the molecular reasons for this inefficiency remain unknown. IVF and embryo transfer (IVF-embryo transfer) also results in a high frequency of implantation failures and early spontaneous abortions. Here we show that the anandamide (AEA)-degrading enzyme, fatty acid amide hydrolase (FAAH), had significantly lower activity (46 +/- 17 versus 161 +/- 74 pmol/min per mg protein) and protein content (0.10 +/- 0.03 versus 0.23 +/- 0.06 units) in lymphocytes of IVF-embryo transfer patients who failed to achieve an ongoing pregnancy than in those who become pregnant, and this was paralleled by a significant increase in blood AEA (4.0 +/- 2.2 pmol/ml and 0.9 +/- 1.0 pmol/ml respectively). The blood levels of the other endocannabinoid, 2-arachidonoylglycerol, or of the AEA congener, N-palmitoylethanolamine, which are metabolized by enzymes different from FAAH, was not different between the pregnant and nonpregnant women, nor was there any difference in the activity of the AEA membrane transporter or the amounts of cannabinoid receptors in lymphocytes. Taken together with the reported negative effects of AEA on embryo implantation, this study indicates that low FAAH activity and subsequent increased AEA levels in blood might be one of the causes of implantation failure or pregnancy loss, thereby leading to a better understanding of the pathophysiological and therapeutic implications of endocannabinoids in human fertility.
Maccarrone
Mauro
M
Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, I-00133 Rome, Italy. maccarrone@med.uniroma2.it
Bisogno
Tiziana
T
Valensise
Herbert
H
Lazzarin
Natalia
N
Fezza
Filomena
F
Manna
Claudio
C
Di Marzo
Vincenzo
V
Finazzi-Agrò
Alessandro
A
D000328:Adult; D000581:Amidohydrolases / Q000097:blood*; D001095:Arachidonic Acids / Q000097:blood*; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000378:metabolism; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000502:physiology; D004624:Embryo Transfer; D063388:Endocannabinoids; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D053284:Polyunsaturated Alkamides; D011237:Predictive Value of Tests; D011247:Pregnancy; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000502:physiology; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D018997:Chorionic Gonadotropin, beta Subunit, Human; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000099252:Fatty Acid Amide Hydrolases; C078814:anandamide