Enriched endoplasmic reticulum-mitochondria interactions result in mitochondrial dysfunction and apoptosis in oocytes from obese mice

作     者：Lihong Zhao Tengfei Lu Lei Gao Xiangwei Fu Shien Zhu Yunpeng Hou 

作者机构：State Key Laboratory of Agrobiotechnolocjy College of Biolocjical Sciences China Agricultural University Yuanmincjyuan west Rd 2 Bejing100193 China Key Laboratory of Animal Genetics Breeding and Reproduction College of Animal Science and Technology China Agricultural University Beijing China 

出 版 物：《Journal of Animal Science and Biotechnology》 (畜牧与生物技术杂志（英文版）)

年 卷 期：2018年第9卷第1期

页      面：91-98页

核心收录：

学科分类：090601[农学-基础兽医学] 09[农学] 0906[农学-兽医学] 

基　　金：supported by the National Basic Research Program of China[grant number 2014CB138500] 

主　　题：Apoptosis IP3R1 MAM Mitochondrial Ca2+ Obesity Oocyte PACS-2 

摘      要：Background： Maternal obesity alters oocytes and subsequent fetal metabolism. An increasing number of studies have shown that the endoplasmic reticulums（ER） or mitochondria have important effects on oocyte quality, but there has been no study of the effect of mitochondria-associated ER membranes（MAMs） on oocyte quality. The present study was designed to assess whether the level of MAM and MAM-related proteins were different in oocytes from obese and control ***： First, oocytes from mice with high-fat-diet（HFD）-induced obesity had higher levels（either greater numbers or a higher proportion for the same numbers） of MAM than oocytes from control mice. The abundance of MAM-related proteins in oocytes from obese mice was significantly greater at both the messenger RNA and protein levels, including inositol 1,4,5-trisphosphate receptor, type 1（IP3R1）, inositol 1,4,5-trisphosphate receptor,type 2（IP3 R2） and phosphofurin acidic cluster sorting protein 2（PACS-2）. Further, there was an increase in mitochondrial Ca^（2＋）（[Ca^（2＋）]_m） which was associated with increased apoptosis and compromised cytoplasmic maturation in oocytes from obese mice. Down-regulation of MAM-related protein IP3R1 in oocytes from obese mice decreased [Ca^2＋]_mand apoptosis and improved cytoplasmic maturation but did not reduce the overal MAM level. However, down-regulating MAM-related protein PACS-2 in oocytes from obese mice did reduce the level of MAM and [Ca^（2＋）]_m, which decreased the rate of apoptosis and improved cytoplasmic maturation of oocytes from obese ***： It is possible that enriched MAM could increase [Ca^（2＋）]_m, and this increase has been found to be associated with increased apoptosis and compromised cytoplasmic maturation in oocytes from obese mice. This finding suggests a novel therapeutic target for obesity-induced oocyte defects.