Modulation of the novel cannabinoid receptor - GPR55 - during rat fetoplacental development.

ABSTRACT

Decidualization process involves the morphological and functional transformation of endometrial stromal cells into decidual cells. This is a finely regulated process, which involves proliferation and differentiation of stromal cells into decidual cells, which is followed by regression of the decidual tissue, mainly by apoptosis, necessary to accommodate the growing embryo. Together with the endogenous cannabinoids (ECs) and the respective metabolizing-enzymes, the cannabinoid receptors complete the endocannabinoid system (ECS). Two cannabinoid receptors have been described so far, CB1 and CB2, though a third has been suggested, CB3. Although the ECS role in several biological functions, including reproductive processes, is now well documented, the current state of knowledge about this system is still incomplete. In order to investigate the expression of GPR55, referred as the novel cannabinoid receptor 3 (CB3), in the uterine maternal tissues during normal pregnancy we analysed its expression by Q-PCR, Western blot and immunohistochemistry during fetoplacental period. We found higher protein levels on day 14, after full development of mesometrial decidua. In addition, GPR55 was found in uterine natural killer (uNK) cells pointing to an involvement in the immunological reactions that occur during pregnancy. The prominent expression of GPR55 in decidual cells suggests a role in mediating cannabinoid signalling during fetoplacental development. Additionally, we have studied the effects resulting from its activation in primary decidual cell cultures, which revealed a potential modulation of cell viability through GPR55. The data presented here may clarify the role of GPR55 in fetoplacental development and highlights the presence of a new target for cannabinoid signalling during pregnancy.