抄録
[Introduction] Postpartum uterine infections with bacteria and the release of peptidoglycan (PGN), antigenic cell wall components of both Gram-negative and Gram-positive bacteria, can cause early pregnancy losses in ruminants but with unknown mechanism. Blastocyst-secreted interferon-tau (IFNT) induces upregulation of interferon-stimulated genes (ISGs) via STAT signaling pathway for uterine receptivity and early maternal recognition of pregnancy (MRP) in cows. This study investigated the potential of extremely low levels of PGN to disrupt MRP by modulating endometrial ISGs expression in response to embryo-derived IFNT. [Materials and methods] Cultured bovine endometrial epithelial cells (BEECs) were treated with embryo culture medium (ECM) or IFNT (1 ng/ml) in the presence or absence of PGN (10 pg/ml) for 24 h. To visualize the site of PGN potential in an ex-vivo model, endometrial explants were treated with IFNT (1 ng/ml) in the presence or absence of PGN (10 pg/ml) for 12 h. Cells/explants cultured in media only served as a control. BEECs and explants were analyzed for mRNA expressions of ISGs and STAT1, a key factor for IFNT signaling, by real-time PCR. OAS1 protein was identified by immunofluorescence in explants. [Results] PGN suppressed the upregulation of mRNA expressions of ISGs (ISG15, OAS1) and STAT1, induced by ECM or IFNT, in both BEECs and explants. PGN suppressed the IFNT-triggered intensive OAS1 protein expression throughout the whole luminal epithelium. Moreover, PGN suppressed the stimulatory effect of IFNT on STAT1 mRNA expressions in BEECs. Interestingly, PGN did not stimulate mRNA expressions of the pro-inflammatory cytokines (TNFA and IL1B) or TLR2 in BEECs or explants. These findings indicate that the presence of low levels of PGN (10 pg/ml) suppresses early embryo-derived IFNT signals for ISGs expression in the bovine endometrium and thereby, interferes with endometrial epithelium receptivity and early MRP in cows, which leads to pregnancy failure.
