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 F(2)alpha (
PGF(2)alpha). Cow luteal tissue secretion of
prostaglandins (PG) E (
PGE(1)+
PGE(2)) and
PGF(2)alpha are derived from precursors in membrane
phospholipids. Cow luteal tissue secretion of
PGE and
PGF(2)alpha increased linearly with time in culture with the
PGE: ratio being 1:1.
PGE(1) or
PGE(2) 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,
PGE(1), or
PGF(2)alpha on bovine luteal secretion of
progesterone,
PGE, and
PGF(2)alphain vitro.
PGE and
PGF(2)alpha was increased (P< or =0.05) with time in culture, while
progesterone did not change (P> or =0.05) with time in vehicle-treated luteal slices in vitro.
Progesterone was increased (P< or =0.05) by
PGE(1) and decreased (P< or =0.05) by
PGF(2)alpha, CB(1) or CB(2) receptor agonists, or a FAAH inhibitor. Both
PGE and
PGF(2)alpha were decreased (P< or =0.05) by CB(1) or CB(2) 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.