Bacterial Lipopolysaccharide Induces an Endocrine Switch from Prostaglandin F2α to Prostaglandin E2 in Bovine Endometrium

Abstract

Escherichia coli infection of the endometrium causes uterine disease after parturition and is associated with prolonged luteal phases of the ovarian cycle in cattle. Termination of the luteal phase is initiated by prostaglandin F(2alpha) (PGF) from oxytocin-stimulated endometrial epithelial cells. Compared with normal animals, the peripheral plasma of animals with E. coli infection of the endometrium had higher concentrations of lipopolysaccharide (LPS) and prostaglandin E(2) (PGE) but not PGF. Endometrial explants accumulated predominantly PGE in the culture medium in response to LPS, and this effect was not reversed by oxytocin. Endometrial cells expressed the Toll-like receptor 4/CD14/MD-2 receptor complex necessary to detect LPS. Epithelial and stromal cells treated with LPS had higher steady-state media concentrations of PGE rather than PGF. Arachadonic acid is liberated from cell membranes by phospholipase 2 (PLA2) enzymes and converted to prostaglandins by synthase enzymes. Treatment of epithelial and stromal cells with LPS did not change the levels of PGE or PGF synthase enzymes. However, LPS stimulated increased levels of PLA2 group VI but not PLA2 group IV C immunoreactive protein in epithelial cells. Endometrial cells expressed the E prostanoid 2 and E prostanoid 4 receptors necessary to respond to PGE, which regulates inflammation as well as being luteotropic. In conclusion, LPS detection by endometrial cells stimulated the accumulation of PGE rather than PGF, providing a mechanism to explain prolonged luteal phases in animals with uterine disease, and this PGE may also be important for regulating inflammatory responses in the endometrium.

Parturition to resumption of ovarian cyclicity: comparative aspects of beef and dairy cows

“…Furthermore, in the animals that ovulated, the CL was smaller and produced less progesterone (Figure 6; . Within the uterus E. coli may disrupt the mechanisms of PG-induced luteolysis in cyclic cows and therefore contribute to prolonged luteal phases by switching PG synthesis away from PGF2α towards PGE 2 (Herath et al, 2009;Williams et al, 2008b). These observations show a direct correlation between the presence of uterine pathogens, particularly E. coli, on day 7 postpartum and suboptimal ovarian function for the following 3 weeks.…”

BVDV alters uterine prostaglandin production during pregnancy recognition in cows

“…The columns labelled with different letters significantly different at P < 0.05 - 0.01 (a > b > c). (Lewis 2003, Herath et al 2009, this switch provides a mechanism whereby BVDV infection can predispose affected animals to uterine infection. Similarly, bacterial LPS treatment increased PGE 2 production and decreased PGF 2α production in bovine endometrium (Herath et al 2009).…”

“…(Lewis 2003, Herath et al 2009, this switch provides a mechanism whereby BVDV infection can predispose affected animals to uterine infection. Similarly, bacterial LPS treatment increased PGE 2 production and decreased PGF 2α production in bovine endometrium (Herath et al 2009). Our previous studies demonstrated that numerous innate immune responses mounted following an LPS challenge was also significantly suppressed in ncpBVDV-infected bovine uterine endometrial cells (Oguejiofor et al 2015a).…”

Innate immunity and inflammation of the bovine female reproductive tract in health and disease

“…However, a range of cells other than 'professional' immune cells also express pattern recognition receptors. For example, endometrial epithelial and stromal cells express the TLR4-CD14-MD2 receptor complex necessary to detect LPS, and respond to LPS by secreting IL6, IL8 and prostaglandin E 2 (Herath et al 2009a, Cronin et al 2012. So, the overall inflammatory response to pathogens associated with innate immunity depends on the sum of the actions of multiple cell types rather than just specialised immune cells.…”