PI3K inhibitor reduces in vitro maturation and developmental competence of porcine oocytes

Abstract

The phosphatidylinositol -3- kinase (PI3K) signaling pathway is critical for the cell proliferation, apoptosis, metabolism, DNA repair and protein synthesis. Significant effort has focused on elucidating the relationship between PI3K signaling pathway and other nuclear signal transducers; However, little is known about the connection between PI3K signaling pathway and porcine oocyte meiotic maturation. In this study, we investigated the function of PI3K signaling pathway in porcine oocytes. PI3K signaling pathway was important during oocyte maturation. Furthermore, the PI3K signaling pathway inhibitor LY-294002 blocked porcine oocyte maturation, reducing the percentage of oocytes that first polar body (PBI) extrusion. LY-294002 also decreased the expression of oocyte proliferation-related gene PCNA and reduced the mRNA and protein levels of PI3K. What's more, LY-294002 also decreased other maturation-related genes that are predominantly expressed duringporcine oocyte maturation, including bone morphogenetic protein 15 (BPM15), growth differentiation factor 9 (GDF9), cell division cycle protein 2 (CDC2), phosphatase and tensin homolog (PTEN), CyclinB1, MOS and Akt. LY-294002 treatment decreased the developmental potential of blastocysts following parthenogenetic activation, increased the level of cell apoptosis and reduced the level of cell-cycle. This study revealed that inhibiting the PI3K signaling pathway could reduce in vitro maturation and developmental competence of porcine oocytes, probably by reducing cell cycle arrest and proliferation, promoting the oocyte apoptosis, and altering the expression of other maternal genes.

Keywords: In vitro maturation; LY-294002; Phosphatidylinositol -3- kinase; Porcine oocyte.