A Novel Integrated View of the Role of Prostaglandins for Recognition and Establishment of Pregnancy in Ruminants

Abstract

Prostaglandins are important regulators of fertility in most mammals. Prostaglandins F₂α (PGF₂α) and E₂ (PGE₂) appear as the most active PGs in reproduction and often mediate opposite reactions at the time of establishment and termination of pregnancy. These prostaglandins and possibly also prostacyclin (PGI₂) are responsible for the regulation of luteolysis, implantation, and parturition. In cows, endometrial PGF₂α is the luteolytic hormone whereas PGE, may favour maternal recognition of pregnancy. During the bovine oestrous cycle, days 16-17 are considered as the "critical period" for either maternal recognition of pregnancy (MRP), in the presence of a viable embryo or luteolysis and return to a new oestrous cycle. In ruminants, trophoblastic interferon tau (IFNt) is known as the pregnancy recognition signal. We have found over the years that the mechanism of MRP is more complex than initially anticipated and involves regulation of PG action at the level of biosynthesis, catabolism, transport and receptors. For instance, in the bovine endometrium where the production of PGF₂α is abundant and tightly modulated, we have found that the PGF synthase responsible for its production is not the enzyme previously identified in lung or liver but rather an aldose reductase with a new function, AKR1B5. This enzyme and others like PGH synthase 1 and 2 and PGE synthases are also tightly modulated to control the relative concentration of PGF₂α and PGE₂. Moreover, inspite of their lipid structure, PGs diffuse pooriy through plasma membranes because they are charged negatively. We have identified a novel prostaglandin transporter bPGT that is expressed in the genital tract in a spatio-temporal manner in order to allow the transfer of PGs produced at critical periods of the oestrous cycle or during pregnancy. Finally, the action of individual PGs is regulated at the level of their receptors. A good understanding of PG action in the regulation of reproductive function requires that we consider all these factors. We intend to present here an integrated view of PG action on the function of the female genital tract at the critical period of recognition of pregnancy.