Fluctuations of fatty acid amide hydrolase and anandamide levels during the human ovulatory cycle

Implantation is possible within a defined period of the menstrual cycle, referred to as the 'implantation window'. It is during this critical period that proper dialog can be established between the blastocyst and a receptive endometrium. If for any reason this dialog is not established or is altered, the embryo is aborted. The factors responsible for the interaction between the embryo and the mother at the moment of implantation remain poorly understood. Recent studies indicate that endocannabinoids may contribute to the development of an adequate milieu at the implantation site. Here we show that the levels of anandamide and of its degrading enzyme, the fatty acid amide hydrolase, in peripheral lymphocytes undergo specific variations during the various phases of the human ovulatory cycle. In particular, we found the highest levels of fatty acid amide hydrolase activity and protein content, parallelled by the lowest anandamide concentrations, in the period that temporally coincides with the putative window of implantation in humans. On the other hand, the anandamide-synthesizing phospholipase D, the anandamide membrane transporter and the anandamide-binding cannabinoid receptors of lymphocytes did not change during the menstrual cycle. This study indicates that high fatty acid amide hydrolase activity and low anandamide levels may be among the factors that co-operate in the success of implantation. This would add to our understanding of the pathophysiological and therapeutic implications of the endocannabinoid system in human fertility.