REGULATION OF THE ENDOCANNABINOID SYSTEM DURING EARLY PREGNANCY IN THE RAT.

RIBEIRO ML; BILLI S; SORDELLI M; VERCELLI C; FRANCHI A

Santiago, Chile

Congreso; SLIMP 2004; 2005

Placenta Association for the Americas

Anandamide (AEA) is synthesized by the murine uterus during early pregnancy. High AEA is toxic for the embryo and the implantation process. It is well known that estradiol (E) peaks prior to implantation. We have previously observed that AEA synthesis is highest during estrous in the rat uterus. Thus, the aims of the present work were to characterize AEA synthesis during early pregnancy and if it is regulated by progesterone (P) and E. Methods: Wistar control rats were sacrificed on days 1 to 6 of gestation. Another group of Wistar rats were ovariectomized on day 4 of gestation, treated with vehicle, P (2 mg/kg) or E (0.1 mg/kg) and sacrificed on day 8 of pregnancy (delayed implantation model). The uterine tissue was obtained. AEA synthesis was determined by the conversion of [14C]-arachidonic acid into [14C]-AEA. Results: During early pregnancy, AEA production remained constant until day 5 of gestation (1.40±0.13 nmoles AEA/mg prot/h), when the peak of E has been reported, and diminished towards day 6 (p<0.01). On day 6, implantation sites showed lower AEA production compared to inter-implantation sites (p<0.05). In the delayed implantation model, P that maintains the uterus in a refractory state to implantation, stimulated AEA synthesis (0.22±0.01 vs 0.35±0.03 nmoles AEA/mg prot/h), while E, that turns the uterus receptive to the blastocysts, did not modify it. Conclusions: These results indicate that in the rat uterus, AEA production is selectively modulated by P and E, suggesting that these ovarian hormones could be regulating the level of AEA during implantation, a crucial step in early gestation and successful pregnancies. Supported by PICT 10901 (Argentina).