Expression And Regulation Of Signal Tranducer And Activator Of Transcription 3 In Mouse Uterus And Corpus Luteum

STAT3 (signal transducer and activator of transcription 3) is important for embryo morphogenesis, cell growth, apoptosis and cell mobility. The aim of this study is to examine STAT3 expression and activation in mouse uterus during early pregnancy, pseudopregnancy, delayed implantation, artificial decidualization and steroid hormonal treatments by situ hybridization and immunohistochemistry. The immature mice were also used to see the expression and regulation of STAT3 by gonadotrophin treatment. Additionally, the expression and regulation of STAT3 were examined during the formation and regression of corpus luteum.The expression of STAT3 mRNA in the luminal and glandular epithelium was considerable stronger on day 1 of pregnancy, and weaker on days 2 to 3. There were strong STAT3 immunostaining in the glandular epithelium and weak nuclear translocation of tyrosine-phosphorylated STAT3 in the luminal epithelium containing a blastocyst in the day 4 morning. In the day 4 afternoon and midnight, STAT3 expression and nuclear translocation of tyrosine-phosphorylated STAT3 became stronger in the glandular and luminal epithelium of the potential implantation sites. There was less nuclear translocation of tyrosine-phosphorylated STAT3 in the luminal epithelium of implantation sites on day 5 of pregnancy. Nuclear translocation of tyrosine-phosphorylated STAT3 was also not detected in the uteri on day 4 of pseudopregnancy and under delayed implantation. These data suggest that an active blastocyst is required for STAT3 activation which may be important for embryo implantation.There were detectable expression and tyrosine-phosphorylation of STAT3 in the decidual cells on days 5 and 6 of pregnancy. On day 8 of pregnancy, STAT3 immunostaining was mainly located in the decidual area near the lumen, and tyrosine-phosphorylated STAT3 immunostaining was seen in the decidual area near the myometrium, being stronger in the mesometrium side. The expression and tyrosine-phosphorylation of STAT3 in the uterus of artificial decidualization were similar to that in day 8 uterus, implying that STAT3 is closely related to decidualization.In the ovariectomized mice, there was no detectable STAT3 expression and activation in the uterus. Progesterone had no effects on STAT3 expression and activation. After estrogen treatment, there were detectable STAT3 mRNA and immunostaining, and weak tyrosine-phosphorylation of STAT3 in the luminal epithelium. If these ovariectomized micewere treated with progesterone for 2 days followed by estrogen treatment for 1 day, the expression of STAT3 and nuclear translocation of tyrosine-phosphorylated STAT3 were significantly increased in the luminal epithelium, suggesting that estrogen and progesterone could jointly initiate STAT3 expression and activation.The expression, tyrosine-phosphorylation and nuclear translocation of STAT3 were increased in the luminal and glandular epithelium of immature mice by PMSG treatments. hCG treatment also stimulated the tyrosine-phosphorylation of STAT3 in the nuclei of luminal epithelium. However, the tyrosine-phosphorylation of STAT3 was weak after PMSG treatment for 48 h followed by hCG treatment.During the corpus luteum regression, STAT3 mRNA is stablely expressed, and STATS immunostaining gradually increased and reached to the highest level in the regressing corpus luteum. Although there was an increase of tyrosine phoshporylation of STAT3, no nuclear translocation was detected, indicating that STAT3 may not act through the phosphorylation of tyrosine-705.In conclusion, these results suggest that the expression and activation of STAT3 may play an important role during embryo implantation and decidualization. Gonadotrophin could regulate the expression and activation of STAT3 in the luminal and glandular epithelium.