Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

Yang, Hee Jung; Hwang, Kyu Ri; Kwon, Hak Cheol; Kim, Haeng Soo; Choi, Kyoo Wan; Oh, Ki Keun

doi:10.1093/humrep/13.4.998

Cited by 446 publications

(294 citation statements)

References 31 publications

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“…Recent studies have shown that vitrification of cleavage embryos resulted in severe loss of methylation in the H19/Igf2 differentially methylated domain (DMD) [20,21] and down-regulation of the expression of Bax, Bcl2 and P53 genes [22]. A recent study revealed high concentration of vitrification solution can affect embryo morphology by increasing the percentage of blastomere fragmentation [23], which is clinically considered as an indicator of decreased embryo viability and developmental ability [24]. However, there is no direct evidence regarding possible effects of cryoprotectant on the hCG secretion.…”

Section: Discussionmentioning

confidence: 99%

Effect of vitrification versus slow freezing of human day 3 embryos on β-hCG levels

Xue¹,

Jiang²,

Zhu³

et al. 2014

J Assist Reprod Genet

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Purpose The study was designed to investigate the effect of vitrification and slow freezing for the cryopreservation of human day 3 embryos on serum β-hCG levels in pregnancies established after frozen embryo transfer (FET). Methods Of the 1384 FET cycles initiated, 1131 embryo transfers met study criteria and assigned to one of two groups: 797 slow-freezing embryo transfers or 334 vitrified embryo transfers. Median values of β-hCG and outcome of all pregnancies were compared between the two groups. Predictive values of serum β-hCG on day 12 after embryo transfer for establishing ongoing pregnancy and pregnancy failure were determined by receiver operating characteristic (ROC) curve analysis. Results In the slow-freezing group, 383 ongoing pregnancies occurred (48.1 %), and transfers of vitrified embryos resulted in 154 pregnancies (46.1 %). Median β-hCG values (279.2 IU/L) for ongoing pregnancies after transfer of vitrified embryos were significantly lower than that of slow frozen embryos (320.5 IU/L). The median values of β-hCG for singleton in the two groups was statistically significant (P<0.05). For slowfreezing embryo transfers, the cut-off value of β-hCG in predicting ongoing pregnancy was 147 IU/L (sensitivity 88.3 %, specificity 80.7 %). For vitrified embryo transfers, the value was 135 IU/L (sensitivity 84.4 %, specificity 76.3 %). Conclusions Day 12 β-hCG levels after FET are significantly affected by the methods of embryo cryopreservation for ongoing pregnancies. Furthermore, when using β-hCG cutoff value to assess pregnancy outcome, the cryopreservation methods should be taken into account.

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Section: Discussionmentioning

confidence: 99%

Effect of vitrification versus slow freezing of human day 3 embryos on β-hCG levels

Xue¹,

Jiang²,

Zhu³

et al. 2014

J Assist Reprod Genet

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“…ROS, such as hydrogen peroxide (H 2 O 2 ) and hydroxyl radical (OH -), can damage cell membranes and DNA and might play a role in apoptosis [47]. In this regard, Yang et al [48] reported a direct relationship between increasing concentrations of H 2 O 2 production and elevated numbers of fragmented embryos, suggesting that ROS may also induce apoptosis in human embryos. In the present study, the proportion of blastocysts that showed DNA fragmentation was significantly lower in the 5 % O 2 group (3.7±1.5) than in the 20 % O 2 group (6.9±3.5) (P<0.05), similar to results reported previously for mouse embryos [49].…”

Section: Discussionmentioning

confidence: 99%

Effects of oxygen tension and IGF-I on HIF-1α protein expression in mouse blastocysts

Yoon

Juhn

et al. 2012

J Assist Reprod Genet

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Purpose Hypoxia inducible factors (HIFs) are key regulators of oxygen homeostasis in response to reduced oxygenation in somatic cells. In addition, HIF-1α protein can be also induced by insulin-like growth factor I (IGF-I) treatment in various cell lines under normoxic condition. However, the expression and function of HIF-1α in embryogenesis are still unclear. Therefore, the objectives of this study were to examine the expression of HIF-1α in mouse blastocysts cultured under hypoxic and normoxic conditions, and to determine whether oxygen tension and IGF-I influence embryonic development through stimulation of HIF-1α expression. Methods Mouse embryos were cultured from the 1-cell to blastocyst stage under 5 % or 20 % O 2 in both the absence and presence of IGF-I. Results The embryonic development rates to the blastocyst stage were not affected by oxygen tension or IGF-I treatment. HIF-1α protein was localized to the cytoplasm of blastocysts, and its levels were independent of oxygen concentration or IGF-I treatment. Blastocysts cultured under 5 % O 2 exhibited significantly higher total cell numbers (83.4±18.1) and lower apoptotic index (3.7±1.5) than those cultured under 20 % O 2 (67.4±15.6) (6.9±3.5) (P<0.05). IGF-I reduced the apoptotic index in both oxygen conditions, but a significant decrease was detected in the 20 % O 2 group. Conclusions HIF-1α may not be a major mediator that responds to change in oxygen tension within blastocysts, inconsistent with that of somatic cells. Supplementation of culture media with IGF-I has been shown to promote embryo development by an anti-apoptotic effect, instead of increasing HIF-1α protein expression.

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“…In humans, oxidative damage of oocytes and granulosa cells was described in the cohort of primordial follicles in women of advanced age (de Bruin et al 2004). ROS perturb the microenvironment in and around ova and granulosa cells and decrease the viability of oocytes and embryos (Miyamoto et al 2010;Van Blerkom et al 1997;Yang et al 1998;Schallreuter et al 1999). By contrast, it has been also demonstrated that ROS, including superoxide and hydrogen peroxide, play critical roles in the regulation of ovarian functions, such as oocyte maturation, folliculogenesis, ovarian steroidogenesis, and luteolysis.…”

Section: Discussionmentioning

confidence: 99%

Age-related Accumulation of Non-heme Ferric and Ferrous Iron in Mouse Ovarian Stroma Visualized by Sensitive Non-heme Iron Histochemistry

Asano

2011

J Histochem Cytochem.

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SummarySensitive non-heme iron histochemistry-namely, the perfusion-Perls method and perfusion-Turnbull method-was applied to study the distribution and age-related accumulation of non-heme ferric iron and ferrous iron in mouse ovary. Light and electron microscopic studies revealed that non-heme ferric iron is distributed predominantly in stromal tissue, especially in macrophages. By contrast, the distribution of non-heme ferrous iron was restricted to a few ovoid macrophages. Aged ovaries exhibited remarkable non-heme iron accumulation in all stromal cells. In particular, non-heme ferrous iron level was increased in stromal tissue, suggestive of increased levels of redox-active iron, which can promote oxidative stress. Moreover, intense localization of both non-heme ferric and ferrous iron was observed in aggregated large stromal cells that were then characterized as ceroid-laden enlarged macrophages with frothy cytoplasm. Intraperitoneal iron overload in adult mice resulted in non-heme iron deposition in the entire stroma and generation of enlarged macrophages, suggesting that excessive iron accumulation induced macrophage morphological changes. The data indicated that non-heme iron accumulation in ovarian stromal tissue may be related to aging of the ovary due to increasing oxidative stress. (J Histochem Cytochem 60:229-242, 2012) Keywords non-heme iron, ovary, aging, macrophage, sensitive non-heme iron histochemistry Article

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Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

Cited by 446 publications

References 31 publications

Effect of vitrification versus slow freezing of human day 3 embryos on β-hCG levels

Effect of vitrification versus slow freezing of human day 3 embryos on β-hCG levels

Effects of oxygen tension and IGF-I on HIF-1α protein expression in mouse blastocysts

Age-related Accumulation of Non-heme Ferric and Ferrous Iron in Mouse Ovarian Stroma Visualized by Sensitive Non-heme Iron Histochemistry

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