Endocannabinoid 1 and 2 (CB1; CB2) receptor agonists affect negatively cow luteal function in vitro

Thirty to 40% of pregnancies are lost during the first third of pregnancy, which has been hypothesized to be due to inadequate progesterone secretion by the corpus luteum. Loss of luteal progesterone secretion during the estrous cycle is via uterine secretion of prostaglandin F2α (PGF2α). Cow luteal tissue secretion of prostaglandins (PG) E (PGE1 + PGE2) and PGF2α are derived from precursors in membrane phospholipids. Cow luteal tissue secretion of PGE and PGF2α increased linearly with time in culture with the PGE: ratio being 1:1. PGE1 or PGE2 are luteotropic in cows and ewes and antiluteolytic in vitro and in vivo in ewes. Endocannabinoids are also derived from phospholipids and are associated with infertility, presumably by reducing implantation; however, effects of endocannabinoids on luteal function have not been addressed. The objective of this experiment was to determine the effects of endocannabinoid type 1 and 2 receptor agonists and receptor antagonists or a fatty acid amide hydrolase (FAAH; catabolizes endocannabinoids) inhibitor, PGE1, or PGF2α on bovine luteal secretion of progesterone, PGE, and PGF2α in vitro. PGE and PGF2α was increased (P ≤ 0.05) with time in culture, while progesterone did not change (P ≥ 0.05) with time in vehicle-treated luteal slices in vitro. Progesterone was increased (P ≤ 0.05) by PGE1 and decreased (P ≤ 0.05) by PGF2α, CB1 or CB2 receptor agonists, or a FAAH inhibitor. Both PGE and PGF2α were decreased (P ≤ 0.05) by CB1 or CB2 receptor agonists or a FAAH inhibitor when compared to vehicle controls. It is concluded that endocannabinoid receptor agonists negatively affect cow luteal function in vitro and that the corpus luteum may also be a site for endocannabinoid decreased fertility as well as a reduction in implantation.