IP3R1 is required for meiotic progression and embryonic development by regulating mitochondrial calcium and oxidative damage

Calcium ions (Ca 2+ ) regulate cell proliferation and differentiation and participate in various physiological activities of cells. The calcium transfer protein inositol 1,4,5-triphosphate receptor (IP3R), located between the endoplasmic reticulum (ER) and mitochondria, plays an important role in regulating Ca 2+ levels. However, the mechanism by which IP 3 R1 affects porcine meiotic progression and embryonic development remains unclear. We established a model in porcine oocytes using siRNA-mediated knockdown of IP 3 R1 to investigate the effects of IP 3 R1 on porcine oocyte meiotic progression and embryonic development. The results indicated that a decrease in IP 3 R1 expression significantly enhanced the interaction between the ER and mitochondria. Additionally, the interaction between the ER and the mitochondrial Ca 2+ ([Ca 2+ ] m ) transport network protein IP 3 R1-GRP75-VDAC1 was disrupted. PLA decreased IP 3 R1, weakened the pairwise interaction between IP 3 R1-GRP75 and VDAC1 and significantly enhanced the interaction between GRP75 and VDAC1, resulting in the accumulation of large amounts of [Ca 2+ ] m . These changes led to mitochondrial oxidative stress and reduced ATP production, which hindered the maturation and late development of porcine oocytes and caused apoptosis.