Transport of Prostaglandin F2α Pulses from the Uterus to the Ovary at the Time of Luteolysis in Ruminants Is Regulated by Prostaglandin Transporter-Mediated Mechanisms

Abstract

In ruminants, prostaglandin F2α (PGF2α) is the uterine luteolytic hormone. During luteolysis, PGF2α is synthesized and released from the endometrium in a pulsatile pattern. The unique structure of the vascular utero-ovarian plexus (UOP) allows transport of luteolytic PGF2α pulses directly from the uterus to the ovary, thus bypassing the systemic circulation. However, the underlying molecular mechanism is not known. The objective of the present study was to determine a role for PG transporter protein (PGT) in the compartmental transport of PGF2α from uterus to ovary through the UOP at the time of luteolysis using the sheep as a ruminant model. [3H]PGF2α, with or without a PGT inhibitor, was infused into UOP, and PGF2α transport and PGT protein expression were determined. Results indicate that PGT protein is expressed in tunica intima, tunica media, and tunica adventitia of the utero-ovarian vein and the ovarian artery of the UOP, and the expression levels are higher on d 10–15 compared with d 3–6 of the estrous cycle. Pharmacological inhibition of PGT prevented transport of exogenous [3H]PGF2α as well as oxytocin-induced endogenous luteolytic PGF2α pulse up to 80% from uterine venous blood into ovarian arterial blood through the UOP at the time of luteolysis in sheep. Taken together, these results indicate that at the time of luteolysis, transport of PGF2α from uterus to ovary through the UOP is regulated by PGT-mediated mechanisms. These findings also suggest that impaired PGT-mediated transport of PGF2α from the utero-ovarian vein into the ovarian artery could adversely influence luteolysis and thus affect fertility in ruminants.