Intrauterine Coadministration of ERK1/2 Inhibitor U0126 Inhibits Interferon TAU Action in the Endometrium and Restores Luteolytic PGF2alpha Pulses in Sheep

摘要: In ruminants, prostaglandin F2 alpha (PGF2alpha) is synthesized and released in a pulsatile pattern from the endometrial luminal epithelial (LE) cells during process of luteolysis. Interferon tau (IFNT) Type 1 IFN secreted by trophoblast developing conceptus. IFNT acts locally on LE to inhibit releases PGF2alpha thus establish an endocrine environment for recognition pregnancy. Cell signaling pathways through which stimulates expression multiple genes or proteins are largely unknown. Results present investigation indicate that intrauterine administration inhibits release PGF2alpha, while coadministration ERK 1/2 inhibitor U0126 restores luteolytic pulses sheep. increases phosphorylation ERK1/2 its interaction with PGT LE. Blockade action, decreases pERK1/2 protein interactions, re-establishes spatial oxytocin receptor completely estrogen partially without modulating interferon regulatory factor-2 (IRF-2) does not decrease COX-2, PGDH, Our results provide important new insights into molecular control at time establishment pregnancy ruminants. This novel IFNT-ERK1/2 module needs be explored future studies understand cellular mechanisms action