Prostaglandins play a role in the labor process at term and pre-term in animal species and in primates. Mice lacking the ability to generate prostaglandins (PGHS-1 knock-outs) have protracted labors. The capacity for prostaglandin production by intrauterine tissues increases before the onset of labor. Furthermore, inhibitors of prostaglandin synthesis, such as indomethacin, effectively block uterine contractility and prolong gestation. Prostaglandins, including PGE₂ and PGF_2α, are formed from the obligate precursor arachidonic acid, which is liberated from membrane phospholipids through the activities of one or more isoforms of phospholipase C or phospholipase A₂. Arachidonic acid is converted to prostaglandins through prostaglandin H₂ synthase (PGHS) activity. There are two forms of PGHS: PGHS-1, which is described as constitutive, and PGHS-2, which is inducible by growth factors, cytokines, and glucocorticoids in human fetal membrane cells. Arachidonic acid can also be metabolized to compounds such as leukotrienes. Current evidence suggests that conversion of arachidonic acid to leukotrienes predominates in fetal membranes for much of gestation but decreases at term, at the time of increased PGHS activity, resulting in an increased output of primary prostaglandins.

In turn, the primary prostaglandins are metabolized through a nicotinamide adenine dinucleotide (NAD)–dependent 15-hydroxyprostaglandin dehydrogenase (PGDH) enzyme to inactive metabolites. PGDH activity is especially high in human chorion trophoblast, and this may provide an important metabolic barrier that prevents the passage of unmetabolized pros-taglandins—generated during pregnancy in amnion and chorion—from reaching the underlying decidua and myometrial tissue.

Prostaglandin action is effected through specific receptors, including the four main subtypes of receptors for PGE₂—EP-1, EP-2, EP-3, and EP-4—and the FP receptors for PGF_2α receptors exist in several isoforms produced by alternative splicing of a single gene product. EP-1 and EP-3 receptors mediate contractions of smooth muscle in several tissues through mechanisms that lead to increased calcium mobilization and to inhibition of intracellular cAMP. Activation of EP-2 and EP-4 receptors increases cAMP formation and relaxes smooth muscle. These different receptor subtypes are expressed in human myometrium throughout gestation. Thus, it is evident why a single ligand, PGE₂, may have different effects in different areas of the uterus, producing contractions (through EP-1 and EP-3) or relaxation (through EP-2 or EP-4), wherever a predominance of a particular receptor subtype occurs.

In human pregnancy, prostaglandin production is discretely compartmentalized between layers of the fetal membranes. PGHS activity predominates in amnion, PGE₂ is the major prostaglandin formed, and levels of mRNA and activity of the PGHS-2 isoform increase at the time of labor, both term and preterm. Chorion expresses both PGHS and PGDH enzyme activity. At term parturition, output of prostaglandins from chorion increases as PGHS-2 activity rises and PGDH declines. At preterm labor, activities of both PGHS-1 and PGHS-2 increase in chorion. Both PGHS enzymes are produced in decidua, although little change occurs in the levels of mRNA encoding these enzymes in this tissue at the time of labor. Studies have shown that human myometrium also expresses PGHS enzymes. Whether those prostaglandins that stimulate myometrial contractility are generated in myometrium, decidua, or the amniochorion layers is unclear.