Dataset Information

Age-Associated Lipidome Changes in Metaphase II Mouse Oocytes.

ABSTRACT: The quality of mammalian oocytes declines with age, which negatively affects fertilization and developmental potential. The aging process often accompanies damages to macromolecules such as proteins, DNA, and lipids. To investigate if aged oocytes display an altered lipidome compared to young oocytes, we performed a global lipidomic analysis between oocytes from 4-week-old and 42 to 50-week-old mice. Increased oxidative stress is often considered as one of the main causes of cellular aging. Thus, we set up a group of 4-week-old oocytes treated with hydrogen peroxide (H2O2), a commonly used oxidative stressor, to compare if similar lipid species are altered between aged and oxidative-stressed oocytes. Between young and aged oocytes, we identified 26 decreased and 6 increased lipids in aged oocytes; and between young and H2O2-treated oocytes, we identified 35 decreased and 26 increased lipids in H2O2-treated oocytes. The decreased lipid species in these two comparisons were overlapped, whereas the increased lipid species were distinct. Multiple phospholipid classes, phosphatidic acid (PA), phosphatidylinositol (PI), phosphatidylserine (PS), and lysophosphatidylserine (LPS) significantly decreased both in H2O2-treated and aged oocytes, suggesting that the integrity of plasma membrane is similarly affected under these conditions. In contrast, a dramatic increase in diacylglycerol (DG) was only noted in H2O2-treated oocytes, indicating that the acute effect of H2O2-caused oxidative stress is distinct from aging-associated lipidome alteration. In H2O2-treated oocytes, the expression of lysophosphatidylcholine acyltransferase 1 increased along with increases in phosphatidylcholine. Overall, our data reveal that several classes of phospholipids are affected in aged oocytes, suggesting that the integrity of plasma membrane is associated with maintaining fertilization and developmental potential of mouse oocytes.

SUBMITTER: Mok HJ

PROVIDER: S-EPMC4755615 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Age-Associated Lipidome Changes in Metaphase II Mouse Oocytes.

Mok Hyuck Jun HJ Shin Hyejin H Lee Jae Won JW Lee Geun-Kyung GK Suh Chang Suk CS Kim Kwang Pyo KP Lim Hyunjung Jade HJ

PloS one 20160216 2

The quality of mammalian oocytes declines with age, which negatively affects fertilization and developmental potential. The aging process often accompanies damages to macromolecules such as proteins, DNA, and lipids. To investigate if aged oocytes display an altered lipidome compared to young oocytes, we performed a global lipidomic analysis between oocytes from 4-week-old and 42 to 50-week-old mice. Increased oxidative stress is often considered as one of the main causes of cellular aging. Thus ...[more]

PMID: 26881843

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Project description:BackgroundOocytes may undergo two types of aging. The first is induced by exposure to an aged ovarian microenvironment before being ovulated, known as 'reproductive or maternal aging', and the second by either a prolonged stay in the oviduct before fertilization or in vitro aging prior to insemination, known as 'postovulatory aging'. However, the molecular mechanisms underlying these aging processes remain to be elucidated. As telomere shortening in cultured somatic cells triggers replicative senescence, telomere shortening in oocytes during reproductive and postovulatory aging may predict developmental competence. This study aimed to ascertain the mechanisms underlying altered telomere biology in mouse oocytes during reproductive and postovulatory aging.MethodsWe studied Tert expression patterns, telomerase activity, cytosolic reactive oxygen species (ROS) production, and telomere length in fresh oocytes from young versus reproductively-aged female mice retrieved from oviducts at 14 h post-human chorionic gonadotropin (hCG), in vivo or in vitro postovulatory-aged mouse oocytes at 23 h post-hCG. Oocytes were collected from super-ovulated C57BL/6 J mice of 6-8 weeks or 42-48 weeks of age. mRNA and protein expressions of the Tert gene were quantified using real-time quantitative reverse transcriptase polymerase chain reaction (Q-PCR) and immunochemistry. Telomerase activity was measured by a telomeric repeat amplification protocol assay, while telomere length was measured by Q-PCR and quantitative fluorescence in situ hybridization analyses.ResultsThe abundance of Tert expression in oocytes significantly decreased during reproductive and postovulatory aging. Immunofluorescent staining clearly demonstrated an altered pattern and intensity of TERT protein expression in oocytes during reproductive aging. Furthermore, relative telomerase activity (RTA) in oocytes from reproductively-aged females was significantly lower than that in oocytes from young females. In contrast, RTA in postovulatory-aged oocytes was similar to that in fresh oocytes. Oocytes from reproductively-aged females and postovulatory-aged oocytes showed higher ROS levels than oocytes from young females. Relative telomere length (RTL) was remarkably shorter in oocytes from reproductively-aged females compared to oocytes from young females. However, postovulatory aging had no significant effect on RTL of oocytes.ConclusionsLong-term adverse effects of low telomerase activity and increased ROS exposure are likely associated with telomere shortening in oocytes from reproductively-aged female mice.

Project description:BackgroundAn inverse relationship between oocyte efficiency and ovarian response was reported in conventional IVF. The purpose of this study was to report metaphase II (MII) oocyte efficiency according to oocyte yield in minimal/mild stimulation IVF (mIVF) and to assess whether oocyte yield affects live birth rate (LBR).MethodsInfertile women (n = 264) aged < 39 years old with normal ovarian reserve who had mIVF were recruited. All participants received the same protocol for ovarian stimulation. All the embryos were cultured to the blastocyst stage and vitrified using a freeze-all approach. This was followed by a single blastocyst transferred to each participant in subsequent cycles over a 6-month period. Ovarian response was categorized according to the number of MII oocyte yield (low: 1-2, intermediate: 3-6 and high ≥ 7 MII oocytes). MII oocyte utilization rate was calculated as the number of live births divided by the number of MII oocytes produced after only one oocyte retrieval and subsequent transfers of vitrified/warmed blastocysts. The main outcome measure was cumulative LBR over a 6-month period.ResultsAmong all the participants, 1173 total retrieved oocytes (4.4 ± 0.2 per patient) resulted in 1019 (3.9 ± 0.2 per patient) total MII oocytes, a clinical pregnancy rate of 48.1 % and a LBR of 41.2 %. Oocyte utilization rate was inversely related to ovarian response where it was 30.3 % in the "low" vs. 9.3 % in the "intermediate" vs. 4.3 % in the "high" oocyte yield groups (p < 0.05). Implantation rate significantly dropped as the number of MII oocytes increased and was highest in the "low" oocyte yield group (p < 0.0001). Cumulative LBR was similar in "low," "intermediate," and "high" oocyte yield groups (p > 0.05). The number of MII oocytes had poor sensitivity and specificity for predicting a live birth.ConclusionThese data extend the hypothesis of oocyte efficiency reported in conventional IVF protocols to mIVF protocols.Trial registrationRegistration clinicaltrials.gov: NCT00799929.

Project description:BackgroundMitochondrial DNA (mtDNA) copy number in oocytes correlates with oocyte quality and fertilisation outcome. The introduction of additional copies of mtDNA through mitochondrial supplementation of mtDNA-deficient Sus scrofa oocytes resulted in: (1) improved rates of fertilisation; (2) increased mtDNA copy number in the 2-cell stage embryo; and (3) improved development of the embryo to the blastocyst stage. Furthermore, a subset of genes showed changes in gene expression. However, it is still unknown if mitochondrial supplementation alters global and local DNA methylation patterns during early development.ResultsWe generated a series of embryos in a model animal, Sus scrofa, by intracytoplasmic sperm injection (ICSI) and mitochondrial supplementation in combination with ICSI (mICSI). The DNA methylation status of ICSI- and mICSI-derived blastocysts was analysed by whole genome bisulfite sequencing. At a global level, the additional copies of mtDNA did not affect nuclear DNA methylation profiles of blastocysts, though over 2000 local genomic regions exhibited differential levels of DNA methylation. In terms of the imprinted genes, DNA methylation patterns were conserved in putative imprint control regions; and the gene expression profile of these genes and genes involved in embryonic genome activation were not affected by mitochondrial supplementation. However, 52 genes showed significant differences in expression as demonstrated by RNAseq analysis. The affected gene networks involved haematological system development and function, tissue morphology and cell cycle. Furthermore, seven mtDNA-encoded t-RNAs were downregulated in mICSI-derived blastocysts suggesting that extra copies of mtDNA affected tRNA processing and/or turnover, hence protein synthesis in blastocysts. We also showed a potential association between differentially methylated regions and changes in expression for 55 genes due to mitochondrial supplementation.ConclusionsThe addition of just an extra ~ 800 copies of mtDNA into oocytes can have a significant impact on both gene expression and DNA methylation profiles in Sus scrofa blastocysts by altering the epigenetic programming established during oogenesis. Some of these changes may affect specific tissue-types later in life. Consequently, it is important to determine the longitudinal effect of these molecular changes on growth and development before considering human clinical practice.

Dataset Information

Age-Associated Lipidome Changes in Metaphase II Mouse Oocytes.

Publications

Age-Associated Lipidome Changes in Metaphase II Mouse Oocytes.

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