Reproductive failure and reduced blood pressure in mice lacking the EP2 prostaglandin E-2 receptor

Prostaglandins (PGs) are bioactive lipids that modulate a broad spectrum of biologic processes including reproduction and circulatory homeostasis. Alt hough reproductive functions of mammals are influenced by PGs at numerous l evels, including ovulation, fertilization, implantation, and decidualizatio n, it is not clear which PGs are involved and whether a single mechanism af fects all reproductive functions. Using mice deficient in 1 of 4 prostaglan din E-2 (PGE(2)) receptors - specifically, the EP2 receptor - we show that Ep2(-/-) females are infertile secondary to failure of the released ovum to become fertilized in vivo. Ep2(-/-) ova could be fertilized in vitro, sugg esting that in addition to previously defined roles, PGs may contribute to the microenvironment in which fertilization takes place. In addition to its effects on reproduction, PGE2 regulates regional blood flow in various vas cular beds. However, its role in systemic blood pressure homeostasis is not clear. Mice deficient in the EP2 PGE2 receptor displayed resting systolic blood pressure that was significantly lower than in wild-type controls. Blo od pressure increased in these animals when they were placed on a high-salt diet, suggesting that the EP2 receptor may be these animals when they were placed on a high-salt diet, su,og involved in sodium handling by the kidne y. These studies demonstrate that PGE(2), acting through the EP2 receptor, exerts potent regulatory effects on two major physiologic processes: blood pressure homeostasis and in vivo fertilization of the ovum.