In the horse oviduct the EP receptor was most strongly
In the horse oviduct, the EP2 receptor was most strongly expressed in epithelial Andarine pathway particularly in nonciliated (secretory) epithelial cells as evidenced by IHC. Furthermore, relative amount of EP2 mRNA was greater in the ampulla than in the isthmus, although this likely reflects differences in the relative abundance of mucosa in each of these regions as the epithelia were not separated from the muscularis prior to isolation of RNA in the present study. The distinct immunolocalization of EP2 suggests a possible role in regulation of epithelial secretory function in the horse oviduct (Desantis et al., 2011). Evidence in EP2−/− mice demonstrates a clear role for EP2 in fertility with a reduction in cumulus expansion, reduced ovulation and impaired fertilization (Hizaki et al., 1999, Kennedy et al., 1999). Although much of the effect on fertility in EP2−/− mice was attributed to poor expansion of the cumulus and reduced fertilization rates, it appears likely that alteration in oviductal function may also contribute to the effects of the EP2 knockout in mice.
Overall, EP4 was a less abundant transcript than EP2 across regions and estrous cycle stages in the horse oviduct. Immunolabeling for EP4 was also present in epithelial cells, vascular endothelium, smooth muscle and serosa of the horse oviduct but appeared considerably less than EP2. Expression of EP4 in the oviductal mucosa appeared slightly greater in the apical portion of ciliated epithelial cells with distinct EP4 gene expression noted in single cells localized within the oviductal epithelium. These isolated cells with distinct labeling for EP4 may represent lymphocytes (Brinsko and Ball, 2006) because PGE2/EP4 signaling have been associated with differentiation and expansion of T lymphocytes (Sakata et al., 2010).
The widespread expression of EP2 and EP4 receptor genes in the horse oviduct imply that PGE2 has diverse effects on oviductal function in the horse. Expression of the EP4 receptor in oviductal mucosa suggests that PGE2 may have a role in regulation of ciliary activity as noted in the oviduct of rabbits and hamsters (Hermoso et al., 2001, Verdugo et al., 1980). Similarly, expression of the EP2 and EP4 receptor in circular smooth muscle of the oviduct suggests that these receptors may affect relaxation of the isthmic oviduct and thereby facilitate embryo transit secondary to embryonic secretion of PGE2. As noted earlier PGE2 affects gamete and early embryo transit in several species (Ortega-Moreno, 1995, Viggiano et al., 1992). In horses, embryonic secretion of PGE2 at Day 5 post-ovulation appears to regulate oviductal passage of the embryo into the uterus (Weber et al., 1991a, Weber et al., 1991b) apparently through relaxation of circular smooth muscle in the isthmic oviduct (Weber et al., 1995). Prostaglandin E2 binds specifically to the horse oviduct although there was no difference in binding between days 2 and 5 post-ovulation. There was greater PGE2 binding to the ampullar versus the isthmic oviduct (Weber et al., 1992), possibly reflecting the relatively larger contribution of the mucosa within the ampullar portion of the oviduct and the relatively greater expression of EP2 and EP4 in the ampulla.
Conclusions The current study does not address functional correlates for expression of EP2 and EP4 genes in the horse oviduct. Based on the data presented, there was no apparent differential regulation of expression of these PGE2 receptor genes across estrous cycle stage and in fact, gene expression was similar in tissues collected from prepubertal mares. Prostaglandin E2 has a wide variety of functions which have been identified. In the present study, localization of the EP2 and EP4 receptors to secretory epithelial cells, ciliated epithelial cells, putative lymphocytes, smooth muscle, and vascular endothelium suggest that PGE2 may have a wide variety of effects in the horse oviduct. The effects may include modulation of epithelial secretion, ciliary beat, muscular relaxation, immunomodulation and vasodilation. Future studies will be required to characterize these effects as well as how they are modulated through the EP2 and EP4 receptors.