**5.5 Prostaglandins**

Placentitis is characterized by the production of proinflammatory cytokines (such as IL-6 and IL-8) and PGs [175, 176]. PG release increases uterine contractility and consequently the risk of premature delivery [138]. Proinflammatory cytokines and the PGs of the FPU increases both in response to inflammation/infection, inducing premature activation of the fetal hypothalamic-pituitary-adrenal (HPA) axis [177], accelerating fetal maturation before parturition [138, 178]. The fetal adrenal produces both progestins and, once sufficiently mature, cortisol. Fetal cortisol, in turn, enhances placental and uterine PGs production, further enhancing uterine contractility and resulting in fetal delivery. Since the maturation of the equine fetus occurs later in gestation [137] this implies that placentitis or maternal disease could be devastating to the newborn foal. However, early fetal maturation likely counterbalances premature delivery and may help improve the chances for foal survival [138, 178]. The supplementation with progestin and PG synthetase inhibitor can maintain equine pregnancy in the presence of PGF2 insults [146, 147]. In addition, Esteller-Vico et al. [170] showed that estrogen suppression resulted in a decrease in circulating PGFM, which suggests that estrogens partially regulate PG production during pregnancy since PGFM concentrations were lower but still increased during the last trimester of equine gestation in letrozole-treated mares.
