Effect of Proteasome Pathway on Initiation of Mouse Labor Induced by Antiprogesterone

Problem:  Various kinds of contraction‐associated molecules are up‐regulated at the initiation of labor. However, expression profiling has revealed that many molecules are also down‐regulated. The effect of down‐regulation of molecules by protein degradation on parturition is not known. Methods of study:  We administered lactacystin, a specific proteasome inhibitor, to mouse preterm birth model induced by antiprogesterone RU486 on day 16.0 post‐coitus. NF‐kappaB activity, and the levels of transcripts for oxytocin receptor, prostaglandin F 2 α receptor (FP), cyclooxygenase‐1, ‐2, and interleukin‐1 β in the uterus were examined by electrophoretic mobility shift assay and semi‐quantitative reverse transcriptase‐polymerase chain reaction, respectively. Results:  Administration of lactacystin significantly prolonged the time until the delivery of the first pup. FP mRNA level was solely elevated by RU486 treatment, and lactacystin significantly suppressed this up‐regulation. Conclusions:  Proteolysis by proteasomes in the uterus regulates the initiation of labor, at least in part, via control of contraction‐associated molecules such as FP.