Protection from oxidative stress by thioredoxin and superoxide dismutase of mouse embryos fertilized in vitro

Nonogaki, Takafumi; Noda, Yoichi; Narimoto, Kazutaka; Umaoka, Yoh; Mori, Takahide

doi:10.1093/oxfordjournals.humrep.a137532

Cited by 52 publications

(26 citation statements)

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“…Because preimplantation embryos are sensitive to OS (24), it is believed that a low oxygen condition is conducive to normal embryonic growth and development. This notion is consistent with the finding that antioxidants prevent ROS-induced abnormal embryo growth in culture (25,26). Thus, the embryonic environment facing excess OS interferes with successful implantation.…”

Section: Discussionsupporting

confidence: 91%

Uterine FK506-binding protein 52 (FKBP52)–peroxiredoxin-6 (PRDX6) signaling protects pregnancy from overt oxidative stress

Hirota

Acar

Tranguch

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Immunophilin FK506-binding protein 52 (FKBP52) is a cochaperone that binds to the progesterone receptor (PR) to optimize progesterone (P 4 )-PR signaling. We recently showed that Fkbp52-deficient (Fkbp52 −/− ) mice have reduced uterine PR responsiveness and implantation failure which is rescued by excess P 4 supplementation in a genetic background-dependent manner. This finding led us to hypothesize that FKBP52 has functions in addition to optimizing PR activity. Using proteomics analysis, we found that uterine levels of peroxiredoxin-6 (PRDX6), a unique antioxidant, are significantly lower in Fkbp52 −/− mice than in WT and PR-null (Pgr −/− ) mice. We also found that Fkbp52 −/− mice with reduced uterine PRDX6 levels are susceptible to paraquat-induced oxidative stress (OS), leading to implantation failure even with P 4 supplementation. The same dose of paraquat did not interfere with implantation in WT mice. Moreover, treatment with antioxidants α-tocopherol and N-acetylcysteine (NAC) attenuated paraquat-induced implantation failure in P 4 -treated Fkbp52 −/− mice. Functional analyses using mouse embryonic fibroblasts show that Fkbp52 deficiency associated with reduced PRDX6 levels promotes H 2 O 2 -induced cell death, which is reversed by the addition of NAC or by forced expression of PRDX6, suggesting that Fkbp52 deficiency diminishes the threshold against OS by reducing PRDX6 levels. These findings provide evidence that heightened uterine OS in Fkbp52 −/− females with reduced PRDX6 levels induces implantation failure even in the presence of excess P 4 . This study shows that FKBP52-PRDX6 signaling protects pregnancy from overt OS.embryo implantation | mouse | uterus

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Section: Discussionsupporting

confidence: 91%

Uterine FK506-binding protein 52 (FKBP52)–peroxiredoxin-6 (PRDX6) signaling protects pregnancy from overt oxidative stress

Hirota

Acar

Tranguch

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been shown that in the in vivo condition, ROS production is a usual itinerary in the mitochondrial respiratory chain which is equilibrated by antioxidant defense systems of cells [4,5]. Increased ROS production occurs in the in vitro milieu [18], which is in agreement with results of this study that showed an accrual of ROS formation in cultured preanral follicles up to 96 h. It has been founded that fortifying of the culture medium with antioxidants led to improved culture condition [25,[37][38][39] It has been recommended that ALA beside its main role as a coenzyme of various enzymes like pyruvate dehydrogenase complex that catalyses the utilization of pyruvate in mouse oocytes and follicles [28,29] also acts as a potent antioxidant and able to react directly with ROS [17,36,51]. These observations are in agreement with our data, which showed, ROS levels during IVM of follicles in the presence of ALA were significantly decreased in comparison to the control groups.…”

Section: Discussionsupporting

confidence: 89%

The effect of alpha lipoic acid on the developmental competence of mouse isolated preantral follicles

Talebi

Zavareh

Kashani

et al. 2012

J Assist Reprod Genet

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Purpose This study was designed to investigate the effect of alpha-lipoic acid (ALA) on reactive oxygen species (ROS) production, total antioxidant capacity (TAC) and developmental competence of cultured pre-antral follicles derived from mouse ovarian tissue. Methods Pre-antral follicles were isolated from immature mouse ovaries and were cultured in α-minimal essential medium supplemented with different concentrations (0, 50, 100, 250 and 500 uM) of ALA. Follicular growth, oocyte maturation and embryo development were evaluated. Separately, ROS and TAC were measured after 0, 24, 48, 72 and 96 h of culture with spectrofluorometery and ferric reducing/antioxidant power (FRAP) assay, respectively. Results In the presence of 100 uM ALA, developmental rates of follicles, oocytes and embryos were significantly higher than other groups (p<0.05). At 96 h after culture, a decrease in ROS and an increase in TAC were observed in ALA group compared to control group (p<0.05). Conclusion ALA (100 uM) improves the in vitro development of follicles. This effect may be mediated by decreasing ROS concentration and increasing follicular TAC level during the culture period.

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“…In somatic cells, the overexpression of H6PD induces the expression of prooxidative enzymes (Leopold et al 2003, Park et al 2006, which is consistent with the overexpression of thioredoxin (TXN) in our parthenotes. The ubiquitous protein disulfide reductase TXN plays a role in the mouse implantation (Nonogaki et al 1991), and responds to oxidative stress in bovine and mouse embryos (Nonogaki et al 1991, Bing et al 2003. The TXN gene is downregulated in embryos that fail to give pregnancies and those leading to resorption (El-Sayed et al 2006), while the addition of the compound to a pig embryo culture improves blastocyst formation, cell numbers, and apoptosis (Ozawa et al 2006).…”

Section: Development and Gene Expression In Parthenotesmentioning

confidence: 99%

Biological differences between in vitro produced bovine embryos and parthenotes

Gómez¹,

Gutiérrez‐Adán²,

Díez³

et al. 2009

Reproduction

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Parthenotes may represent an alternate ethical source of stem cells, once biological differences between parthenotes and embryos can be understood. In this study, we analyzed development, trophectoderm (TE) differentiation, apoptosis/necrosis, and ploidy in parthenotes and in vitro produced bovine embryos. Subsequently, using real-time PCR, we analyzed the expression of genes expected to underlie the observed differences at the blastocyst stage. In vitro matured oocytes were either fertilized or activated with ionomycin C6-DMAP and cultured in simple medium. Parthenotes showed enhanced blastocyst development and diploidy and reduced TE cell counts. Apoptotic and necrotic indexes did not vary, but parthenotes evidenced a higher relative proportion of apoptotic cells between inner cell mass and TE. The pluripotence-related POU5F1 and the methylation DNMT3A genes were downregulated in parthenotes. Among pregnancy recognition genes, TP-1 was upregulated in parthenotes, while PGRMC1 and PLAC8 did not change. Expression of p66 shc and BAX/BCL2 ratio were higher, and p53 lower, in parthenotes. Among metabolism genes, SLC2A1 was downregulated, while AKR1B1, PTGS2, H6PD, and TXN were upregulated in parthenotes, and SLC2A5 did not differ. Among genes involved in compaction/blastulation, GJA1 was downregulated in parthenotes, but no differences were detected within ATP1A1 and CDH1. Within parthenotes, the expression levels of SLC2A1, TP-1, and H6PD, and possibly AKR1B1, resemble patterns described in female embryos. The pro-apoptotic profile is more pronounced in parthenotes than in embryos, which may differ in their way to channel apoptotic stimuli, through p66 shc and p53respectively, and in their mechanisms to control pluripotency and de novo methylation.Reproduction (2009) 137 285-295

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Protection from oxidative stress by thioredoxin and superoxide dismutase of mouse embryos fertilized in vitro

Cited by 52 publications

References 0 publications

Uterine FK506-binding protein 52 (FKBP52)–peroxiredoxin-6 (PRDX6) signaling protects pregnancy from overt oxidative stress

Uterine FK506-binding protein 52 (FKBP52)–peroxiredoxin-6 (PRDX6) signaling protects pregnancy from overt oxidative stress

The effect of alpha lipoic acid on the developmental competence of mouse isolated preantral follicles

Biological differences between in vitro produced bovine embryos and parthenotes

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