Dynamic Changes in pStat3 are Involved in Meiotic Spindle Assembly in Mouse Oocytes

The signal transducer and activator of transcription 3 (Stat3) is activated upon phosphorylation at Y705 (pStat3) and serves the dual function of signal transduction and transcription activation. Our previous study suggested that pStat3 is functional during oocyte maturation when transcription is silenced. Therefore, we speculated that pStat3 serves other functions. Immunocytochemical analysis revealed that pStat3 emerges at microtubule asters and spindle and is subsequently localized at the spindle poles along with pericentrin during mouse oocyte maturation. Both Stat3 and pStat3 proteins were detected in conditionally knocked out Stat3^-/- mouse oocytes. pStat3 localization was the same in Stat3^+/+ and Stat3^-/-oocytes, and oocyte maturation proceeded normally, suggesting that pStat3 was still functional. Furthermore, the treatment of oocytes with the Stat3-specific inhibitors stattic and BP-1-102 or anti-pStat3 antibody led to significantly abnormal spindle assembly and chromosome mislocation in a dose-dependent manner, and pStat3 was either absent or improperly localized in these oocytes. Moreover, the development of pre-implantation stage embryos derived from inhibitor-treated oocytes was significantly hampered following in vitro fertilization. These findings indicate a novel function of pStat3 in spindle assembly.