Abstract
Among prostaglandins, Prostaglandin E2 (PGE2) (PGE2) is considered especially important for decidualization, ovulation, implantation and pregnancy. Four major PGE2 receptor subtypes, EP1, EP2, EP3, EP4, as well as peroxisome proliferator-activated receptors (PPARs), mediate various PGE2 effects via their coupling to distinct signaling pathways. This review summarizes up-to-date literatures on the role of prostaglandin E2 receptors in female reproduction, which could provide a broad perspective to guide further research in this field. PGE2 plays an indispensable role in decidualization, ovulation, implantation and pregnancy. However, the precise mechanism of Prostaglandin E2 (EP) receptors in the female reproductive system is still limited. More investigations should be performed on the mechanism of EP receptors in the pathological states, and the possibility of EP agonists or antagonists clinically used in improving reproductive disorders.
Highlights
Prostaglandin (PG) E2, one of the prostanoid family, is a lipid mediator formed commonly in human bodies, and it plays the central role in female fertilization [1]
The most important one is that EP4, rather than EP2, couples to Gi/Go and is responsible for the subsequent phosphoinositide-3 kinase (PI3K) pathway, E2 receptors (EPs) receptors and peroxisome proliferator-activated receptors (PPARs) can be expressed in the endometrium, the ovary, and placenta [13,14]
EP1, EP2 and EP4 agonists promote the migration of HTR-8/SVneo cells, and Leukemia inflammatory inhibitor (LIF) stimulates the expression of EP1, EP2 and EP4 to benefit extravillous trophoblast (EVT) invasion in the first trimester of pregnancy [74]
Summary
Prostaglandin (PG) E2, one of the prostanoid family, is a lipid mediator formed commonly in human bodies, and it plays the central role in female fertilization [1]. PGE2 plays an indispensable role in decidualization, ovulation, implantation and pregnancy. PGE2 is transported across the plasma membrane by multidrug resistance protein 4 (MRP4) [10] and activates its receptors. Gq and activates the PLC/DAG/PKC pathway to stimulate NF-κB gene expression. 1; inhibitor; Gq—G-protein alpha q; Gs—G alpha stimulator; PAI-1—plasminogen activator. The most important one is that EP4, rather than EP2, couples to Gi/Go and is responsible for the subsequent PI3K pathway, EP receptors and PPARs can be expressed in the endometrium, the ovary, and placenta [13,14]. COX-2−/− female mice showed a reduction in ovulation and severe failure in fertilization, implantation and decidualization [15], implying that COX-2-generated prostaglandins and their receptors play an important role in female reproduction. We attempt to summarize present knowledge of prostaglandin E2 receptors in the regulating of various physiological and pathological states of female reproduction
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