Intraluteal Prostaglandin Biosynthesis and Signaling Are Selectively Directed Towards PGF2alpha During Luteolysis but Towards PGE2 During the Establishment of Pregnancy in Sheep1

ABSTRACT In ruminants, endometrial prostalgandin (PG) F2alpha causes functional luteolysis, whereas luteal synthesis of PGF2alpha is required for structural luteolysis. PGE2 is considered to be a luteoprotective mediator. Molecular aspects of luteal PGF2alpha and PGE2 biosynthesis and signaling during the estrous cycle and establishment of pregnancy are largely unknown. The objectives of the present study were 1) to determine the regulation of proteins involved in PGF2alpha and PGE2 biosynthesis, catabolism, transport and signaling in the corpus luteum (CL); 2) to investigate the transport of interferon tau (IFNT), PGF2alpha, and PGE2 from the uterus to the ovary through the vascular utero-ovarian plexus (UOP); and 3) to compare the intraluteal production of PGF2alpha and PGE2 on Days 12, 14, and 16 of the estrous cycle and pregnancy in sheep. Our results indicate that luteal PG biosynthesis is selectively directed towards PGF2alpha at the time of luteolysis and towards PGE2 during the establishment of pregnancy. Moreover, the ability of the CL of early pregnancy to resist luteolysis is due to increased intraluteal biosynthesis of PGE2 and PGE2 receptor (PTGER) 2 (also known as EP2)- and PTGER4 (also known as EP4)-mediated signaling. We also found that IFNT protein is not transported through the UOP from the uterus to the ovary; in contrast, a large proportion of endometrial PGE2 is transported from the uterus to the ovary through the UOP. These results indicate that endometrial PGE2 stimulated by pregnancy is transported locally to the ovary, which increases luteal PGE2 biosynthesis and hence activates luteal PTGER2 and PTGER4 signaling, thus protecting the CL during the establishment of pregnancy in sheep.