Oestrous cycle-related changes in production of Toll-like receptors and prostaglandins in the canine endometrium

The objectives of this study were to evaluate the following events in the canine endometrium over the course of the oestrous cycle: (i) the transcriptional profiles of genes encoding the Toll-like receptors (TLR1–TLR7 and TLR9); (ii) the transcription and protein expression levels of TLR2 and TLR4; (iii) the gene transcription profile of prostaglandin synthesis enzymes (PTGS2, PGES and PGFS); (iv) the response pattern of PGF2α and PGE2 following exposure of endometrial explants to LPS and LTA. TLR1–TLR7 and TLR9 genes were transcribed in the endometrium of bitches throughout the oestrous cycle, which indicates that TLR-mediated immune surveillance is an important component of the defence mechanisms within the uterus. Canine endometrial mRNA and protein expression of TLR2 and TLR4 was up-regulated at the late dioestrus and anoestrus and was the lowest in the follicular phase and early dioestrus. The decreased mRNA and protein levels observed at early dioestrus may favour implantation, but may also be linked to the high prevalence of pyometra at this stage of the oestrous cycle. After LPS and LTA stimulation, endometrial explants produced more PGF2α than PGE2, which may be related to the early demise of the corpus luteum observed in vivo in canine pyometra cases. Overall, these results indicate that TLRs are involved in the activation of the inflammatory response associated with pyometra in the bitch. TLRs may therefore be therapeutic targets for the control of uterine bacterial infections in the bitch and potentially in other species.