Interferon-τ regulates prostaglandin release in goat endometrial stromal cells via JAB1 - unfolded protein response pathway

Prostaglandins (PGs) are major products of the uterine endometrium, and they are critical for recognition of pregnancy in ruminants. During the peri-implantation period of pregnancy, interferon tau (IFN-τ) plays an important role in the regulation of endometrial PGs synthesis, but the underlying mechanisms remain poorly understood. In this work, the results demonstrated that IFN-τ increased the PGE2/PGF2α ratio, up-regulated the expression of JAB1 and activated the unfolded protein response (UPR). Knockdown of JAB1 reduced the PGE2/PGF2α ratio and inhibited the expression of UPR markers in endometrial stromal cells (ESCs) under IFN-τ treatment. Pre-treatment with endoplasmic reticulum (ER) stress activator thapsigargin (Tg) activated UPR and restored the PGE2/PGF2α ratio in shJAB1 groups under IFN-τ treatment. In conclusion, our results indicated that IFN-τ regulated the PGE2/PGF2α ratio via cooperation between JAB1 and UPR, and the reduction of JAB1 led to the down-regulation of the PGE2/PGF2α ratio, which inhibits UPR, and thus is harmful to early pregnancy. Activation of UPR could restore JAB1 reduction, resulting in a reduced PGE2/PGF2α ratio. These findings extend our understanding and may provide new insights into the mechanism of IFN-τ regulation of PG secretion in ESCs and the biological functions of JAB1 and UPR.