IP3R1 regulates calcium balance in porcine oocyte maturation and early embryonic development

Chang Zhang; Lepeng Gao; Deyi Wu; Guoxia Wang; Hainan Lan; Liu Li; Xin Zheng; Suo Li

doi:10.1016/j.theriogenology.2023.06.021

IP₃R1 regulates calcium balance in porcine oocyte maturation and early embryonic development

Theriogenology. 2023 Oct 1:209:151-161. doi: 10.1016/j.theriogenology.2023.06.021. Epub 2023 Jun 22.

Authors

Chang Zhang¹, Lepeng Gao¹, Deyi Wu¹, Guoxia Wang¹, Hainan Lan¹, Liu Li², Xin Zheng¹, Suo Li³

Affiliations

¹ College of Animal Science and Technology, Jilin Agricultural University, Xincheng Street 2888, Changchun, 130118, China.
² The Department of Frensic Medicine, College of Basic Medical Sciences, Jilin University, Changchun, 130118, China.
³ College of Animal Science and Technology, Jilin Agricultural University, Xincheng Street 2888, Changchun, 130118, China. Electronic address: wonderful8899@163.com.

PMID: 37393745
DOI: 10.1016/j.theriogenology.2023.06.021

Abstract

The dynamic balance of Ca²⁺ in oocytes promotes the recovery of the meiotic arrest phase, consequently promoting oocyte maturation. Hence, the analysis of the maintenance and role of calcium homeostasis in oocytes has important guiding significance for obtaining high-quality eggs and maintaining the development of preimplantation embryos. Inositol 1,4,5-trisphosphate receptors (IP₃Rs) are calcium channel proteins that regulate the dynamic balance between the endoplasmic reticulum (ER) and mitochondrial Ca²⁺. Nevertheless, the expression and role of IP₃R in normal pig oocytes have not been reported, and other studies have focused on the role of IP₃R in damaged cells. The purpose of this study was to investigate the potential role of IP₃R in regulating calcium homeostasis in oocyte maturation and early embryonic development. Our results showed that IP₃R1 is stably expressed at different stages of porcine oocyte meiosis, IP₃R1 gradually converges to the cortex, and cortical clusters are formed in MII stages. The loss of IP₃R1 activity contributeds to the failure of porcine oocyte maturation and cumulus cell expansion, as well as the obstruction of polar body excretion. Further analysis showed that IP₃R1 plays an important role in affecting calcium balance by regulating the IP₃R1-GRP75-VDAC1 channel between mitochondria and the endoplasmic reticulum (ER) during porcine oocyte maturation. Inhibiting IP₃R1 expression-induced ER dysfunction, contributeding to ER calcium concentration ([Ca²⁺]_ER) release outwards into mitochondria and causing mitochondrial free calcium concentration ([Ca²⁺]_m) overload and mitochondrial oxidative stress, which was confirmed by the increase in the level of reactive oxygen species (ROS) and apoptosis. Thereby, IP₃R1 plays an important role in affecting calcium balance by regulating the IP₃R1-GRP75 -VDAC1 channel between mitochondria and the ER during porcine oocyte maturation, inhibiting IP₃R1 expression-induced calcium overload and mitochondrial oxidative stress, and increasing ROS levels and apoptosis.

Keywords: Calcium level; Endoplasmic reticulum; IP(3)R1; Mitochondria; Porcine oocytes.

MeSH terms

Animals
Calcium* / metabolism
Calcium, Dietary
Embryonic Development
Oocytes / physiology
Oogenesis*
Reactive Oxygen Species / metabolism
Swine

Substances

Calcium
Reactive Oxygen Species
Calcium, Dietary