LAUSR

Autophagy, an intracellular recycling system, is essential for the meiotic maturation of porcine oocytes. Multiple studies, sought to reveal the precise mechanism employed, commonly used autophagy inducers, such as rapamycin, which is a mammalian target of rapamycin (mTOR) inhibitor. However, it has a limitation as mTOR plays various roles in cell growth and metabolism beyond autophagy. Trehalose has been reported as a novel mTOR-independent autophagy inducer in many cells. Furthermore, our previous study demonstrated that trehalose supplementation during in vitro maturation of porcine oocytes improves the developmental competence of parthenogenetic embryos possibly via autophagic activation, whereas the underlying mechanisms remain unclear. Therefore, the aim of this study was to address this issue. In this study, we found that trehalose plays a role as an autophagy activator by autophagic flux assay and determined that it promotes PI3K/Akt inhibition and VPS34/mTOR activation by immunoblotting, both in cumulus cells (CCs) and oocytes. However, it is interesting to note that these effects caused by trehalose were worked totally varying between CCs and oocytes. In CCs, the autophagy was activated through the improvement of lysosomal function/autophagic clearance viability by upregulation of coordinated lysosomal expression and regulation genes via PI3K/Akt inhibition. Whereas in oocytes, autophagy was activated via VPS34 induction which directly influences autophagosome formation, and the precise meiotic process was ensured via Akt inhibition and mTOR activation. Taken together, this study provided evidence that trehalose could be used as an autophagy inductor during porcine oocyte maturation based on the revealed mechanism.