Age-Associated Metabolic and Morphologic Changes in Mitochondria of Individual Mouse and Hamster Oocytes

Simsek-Duran, Fatma; Li, Fang; Ford, Wentia; Swanson, R. James; Jones, Howard W.; Castora, Frank J.

doi:10.1371/journal.pone.0064955

Cited by 113 publications

(107 citation statements)

References 36 publications

(40 reference statements)

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“…The results of some ultrastructural and biochemical studies make it clear that the structure and function of the cytoplasmic organelles, particularly mitochondria, of both the oocytes and the granulosa cells, which are critical for fertilization and normal embryonic development, are markedly compromised in the oocytes of older women [34]. This finding is supported by earlier studies on the ATP content [35] and ultrastructure of human oocytes [36] as well as murine [37], bovine [38] and hamster [39] oocytes. Ju and Rudolph reported that the level of telomerase www.fhc.viamedica.pl activity is not sufficient to maintain telomere length of stem cells during aging with increased sensitivity towards senescence or apoptosis induced by telomere shortening [40].…”

Section: Discussionmentioning

confidence: 66%

Effects of maternal age on the expression of mesenchymal stem cell markers in the components of human umbilical cord

Alrefaei

Ayuob

Ali

et al. 2015

Folia Histochem Cytobiol.

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Introduction. Although the human umbilical cord (UC) has been previously considered a medical waste, its use as a main source of fetal stem cells for regenerative medicine applications has increased over the past few years. The aim of the study was to assess the impact of the maternal age on the expression of mesenchymal stem cells (MSC) markers CD105 and CD29 in the different areas of human UC. Material and methods. In this comparative cross sectional study, one hundred term UCs from five maternal age groups (20-45 years) were collected after delivery from healthy mothers and were processed to assess both immuno-and gene expression of CD105 and CD29 surface antigen markers using immunohistochemical and RT-PCR techniques. Results. The immunoexpression of CD105 and CD29 in the amniotic membrane (AM) and Wharton's jelly (WJ), the umbilical artery (UA) and the umbilical vein (UV) showed significant negative correlation with the maternal age (p < 0.001). Reduced amount of cells as well as the studied MSC markers and their gene expression levels were documented in older age mothers. CD105-positive MSCs were more abundant in the UA, whereas CD29-positive MSCs were more abundant in the AM and WJ. Conclusion. The decreased expression of CD105 and CD29 MSCs markers with age suggests that selective isolation of MSCs from Wharton's jelly, umbilical artery or umbilical vein of younger mothers should be recommended.

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Section: Discussionmentioning

confidence: 66%

Effects of maternal age on the expression of mesenchymal stem cell markers in the components of human umbilical cord

Alrefaei

Ayuob

Ali

et al. 2015

Folia Histochem Cytobiol.

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“…The most crucial limiting factor determining the outcome of assisted reproduction is poor-quality oocytes due to ovarian aging in patients seeking infertility treatment. Previous studies have demonstrated that oocyte age is associated with mitochondrial dysfunction [2][3][4]. Mitochondria are maternally inherited organelles that serve as the cell's powerhouses, using oxidative phosphorylation to supply ATP.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA copy number in cumulus cells is a strong predictor of obtaining good-quality embryos after IVF

Ogino

Taniguchi

Sakata

et al. 2016

J Assist Reprod Genet

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Purpose The aim of this study was to establish a simple tool to predict good-quality embryos in in vitro fertilization (IVF) by using cumulus cells (CCs) or peripheral blood cells (PBCs). Methods Mitochondrial DNA was extracted from CCs and PBCs in patients undergoing IVF. Using real-time polymerase chain reaction, mtDNA copy number in a single cell was calculated. Embryo quality was assessed when it was transferred or frozen. Results CCs were obtained from 60 oocyte cumulus-cell complexes (OCCCs) in 30 women, and PBCs were collected from 18 women. For the 30 women in the study, the median age was 37 years old (range, 24-43), and the mean body mass index was 21.4 (standard error, 2.0). mtDNA content of CCs and PBCs was highly correlated (Pearson's r = 0.900, p < 0.0001). The median mtDNA content of CCs for goodand poor-quality embryos was 140 and 57, respectively (p < 0.0001). The median mtDNA content of PBCs for goodand poor-quality embryos was 36 and 13, respectively (p = 0.604). The logistic regression model indicated that mtDNA content in CCs was the only parameter that predicted good-quality embryos (p = 0.020). The receiver operating characteristic curve for obtaining good-quality embryos by mtDNA copy number in CCs had an area under the curve of 0.823, and using a threshold of 86, positive and negative predictive values were 84.4 and 82.1 %, respectively. Conclusions The determination of mtDNA content in CCs can be used to predict good-quality embryos.

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“…Old oocytes are characterized by a sequence of molecular and structural abnormalities, such as dysfunctions of intracellular Ca 2C regulation, [14][15] abnormal changes in mitochondrial structure, 16,17 and chromosome missegregation. 3,8 …”

Section: Introductionmentioning

confidence: 99%

Elevated intracellular pH appears in aged oocytes and causes oocyte aneuploidy associated with the loss of cohesion in mice

Cheng

Tang

et al. 2016

Cell Cycle

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Increases in the aneuploidy rate caused by the deterioration of cohesion with increasing maternal age have been well documented. However, the molecular mechanism for the loss of cohesion in aged oocytes remains unknown. In this study, we found that intracellular pH (pH i ) was elevated in aged oocytes, which might disturb the structure of the cohesin ring to induce aneuploidy. We observed for the first time that full-grown germinal vesicle (GV) oocytes displayed an increase in pH i with advancing age in CD1 mice. Furthermore, during the in vitro oocyte maturation process, the pH i was maintained at a high level, up to »7.6, in 12-month-old mice. Normal pH i is necessary to maintain protein localization and function. Thus, we put forward a hypothesis that the elevated oocyte pH i might be related to the loss of cohesion and the increased aneuploidy in aged mice. Through the in vitro alkalinization treatment of young oocytes, we observed that the increased pH i caused an increase in the aneuploidy rate and the sister inter-kinetochore (iKT) distance associated with the strength of cohesion and caused a decline in the cohesin subunit SMC3 protein level. Young oocytes with elevated pH i exhibited substantially the increase in chromosome misalignment.

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Age-Associated Metabolic and Morphologic Changes in Mitochondria of Individual Mouse and Hamster Oocytes

Cited by 113 publications

References 36 publications

Effects of maternal age on the expression of mesenchymal stem cell markers in the components of human umbilical cord

Effects of maternal age on the expression of mesenchymal stem cell markers in the components of human umbilical cord

Mitochondrial DNA copy number in cumulus cells is a strong predictor of obtaining good-quality embryos after IVF

Elevated intracellular pH appears in aged oocytes and causes oocyte aneuploidy associated with the loss of cohesion in mice

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