Mouse blastocyts release a lipid which activates anandamide hydrolase in intact uterus

M. Maccarrone, M. DeFelici, F. G. Klinger, N. Battista, F. Fezza, E. Dainese, G. Siracusa, A. Finazzi-Agrò

Research output: Contribution to journalArticle


Anandamide (N-arachidonoylethanolamine, AEA) is a major endocannabinoid, known to impair mouse pregnancy and embryo development and to induce apoptosis in blastocysts. Here we show that mouse blastocysts rapidly (within 30 min of culture) release a soluble compound, that increases by ∼2.5-fold the activity of AEA hydrolase (fatty acid amide hydrolase, FAAH) present in the mouse uterus, without affecting FAAH gene expression at the translational level. This 'FAAH activator' was produced by both trophoblast and inner cell mass cells, and its initial biochemical characterization showed that it was fully neutralized by adding lipase to the blastocyst-conditioned medium (BCM), and was potentiated by adding trypsin to BCM. Other proteases, phospholipases A2, C or D, DNAse I or RNAse A were ineffective. BCM did not affect the AEA-synthesizing phospholipase D, the AEA-binding cannabinoid receptors, or the selective AEA membrane transporter in mouse uterus. The FAAH activator was absent in uterine fluid from pregnant mice and could not be identified with any factor known to be released by blastocysts. In fact, platelet-activating factor inhibited non-competitively FAAH in mouse uterus extracts, but not in intact uterine horns, whereas leukotriene B4 or prostaglandins E2 and F2α had no effect. Overall, it can be suggested that blastocysts may protect themselves against the noxious effects of uterine endocannabinoids by locally releasing a lipid able to cross the cell membranes and to activate FAAH. The precise molecular identity of this activator, the first ever reported for FAAH, remains to be elucidated.

Original languageEnglish
Pages (from-to)215-221
Number of pages7
JournalMolecular Human Reproduction
Issue number4
Publication statusPublished - Apr 2004



  • Anandamide
  • Enzyme activation
  • Fertility
  • Hydrolysis
  • Implantation

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Genetics
  • Developmental Biology
  • Embryology
  • Cell Biology

Cite this

Maccarrone, M., DeFelici, M., Klinger, F. G., Battista, N., Fezza, F., Dainese, E., Siracusa, G., & Finazzi-Agrò, A. (2004). Mouse blastocyts release a lipid which activates anandamide hydrolase in intact uterus. Molecular Human Reproduction, 10(4), 215-221.