Dataset Information

Loss of TIGAR Induces Oxidative Stress and Meiotic Defects in Oocytes from Obese Mice.

ABSTRACT: Maternal obesity has been reported to impair oocyte quality in mice, however, the underlying mechanisms remain unclear. In the present study, by conducting a comparative proteomic analysis, we identified a reduced expression of TIGAR (TP53-induced glycolysis and apoptosis regulator) protein in ovulated oocytes from high-fat diet (HFD)-fed mice. Specific depletion of TIGAR in mouse oocytes results in the marked elevation of reactive oxygen species (ROS) levels and the failure of meiotic apparatus assembly. Importantly, forced expression of TIGAR in HFD oocytes not only attenuates ROS production, but also partly prevents spindle disorganization and chromosome misalignment during meiosis. Meantime, we noted that TIGAR knockdown in oocytes induces a strong activation of autophagy, whereas overexpression of TIGAR significantly reduces the LC3 accumulation in HFD oocytes. By anti-oxidant treatment, we further demonstrated that such an autophagic response is dependent on the TIGAR-controlled ROS production. In summary, our data indicate a role for TIGAR in modulating redox homeostasis during oocyte maturation, and uncover that loss of TIGAR is a critical pathway mediating the effects of maternal obesity on oocyte quality.

SUBMITTER: Wang H

PROVIDER: S-EPMC6030723 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Loss of TIGAR Induces Oxidative Stress and Meiotic Defects in Oocytes from Obese Mice.

Wang Haichao H Cheng Qing Q Li Xiaoyan X Hu Feifei F Han Longsen L Zhang Hao H Li Ling L Ge Juan J Ying Xiaoyan X Guo Xuejiang X Wang Qiang Q

Molecular & cellular proteomics : MCP 20180518 7

Maternal obesity has been reported to impair oocyte quality in mice, however, the underlying mechanisms remain unclear. In the present study, by conducting a comparative proteomic analysis, we identified a reduced expression of TIGAR (TP53-induced glycolysis and apoptosis regulator) protein in ovulated oocytes from high-fat diet (HFD)-fed mice. Specific depletion of TIGAR in mouse oocytes results in the marked elevation of reactive oxygen species (ROS) levels and the failure of meiotic apparatus ...[more]

PMID: 29776966

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Project description:BackgroundMaternal obesity is a global issue that has devastating effects across the reproductive spectrum such as meiotic defects in oocytes, consequently worsening pregnancy outcomes. Different studies have shown that such types of meiotic defects originated from the oocytes of obese mothers. Thus, there is an urgent need to develop strategies to reduce the incidence of obesity-related oocyte defects that adversely affect pregnancy outcomes. Multiple growth factors have been identified as directly associated with female reproduction; however, the impact of various growth factors on female fertility in response to obesity remains poorly understood.MethodsThe immature GV-stage oocytes from HFD female mice were collected and cultured in vitro in two different groups (HFD oocytes with and without 50 nM IGF2), however; the oocytes from ND mice were used as a positive control. HFD oocytes treated with or without IGF2 were further used to observe the meiotic structure using different analysis including, the spindle and chromosomal analysis, reactive oxygen species levels, mitochondrial functional activities, and early apoptotic index using immunofluorescence. Additionally, the embryonic developmental competency and embryos quality of IGF2-treated zygotes were also determined.ResultsIn our findings, we observed significantly reduced contents of insulin-like growth factor 2 (IGF2) in the serum and oocytes of obese mice. Our data indicated supplementation of IGF2 in a culture medium improves the blastocyst formation: from 46% in the HFD group to 61% in the HFD + IGF2-treatment group (50 nM IGF2). Moreover, adding IGF2 to the culture medium reduces the reactive oxygen species index and alleviates the frequency of spindle/chromosome defects. We found increased mitochondrial functional activity in oocytes from obese mice after treating the oocytes with IGF2: observed elevated level of adenosine triphosphate, increased mitochondrial distribution, higher mitochondrial membrane potentials, and reduced mitochondrial ultrastructure defects. Furthermore, IGF2 administration also increases the overall protein synthesis and decreases the apoptotic index in oocytes from obese mice.ConclusionsCollectively, our findings are strongly in favor of adding IGF2 in culture medium to overcome obesity-related meiotic structural-developmental defects by helping ameliorate the known sub-optimal culturing conditions that are currently standard with assisted reproduction technologies.

Dataset Information

Loss of TIGAR Induces Oxidative Stress and Meiotic Defects in Oocytes from Obese Mice.

Publications

Loss of TIGAR Induces Oxidative Stress and Meiotic Defects in Oocytes from Obese Mice.

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