Tauroursodeoxycholic acid improves pre-implantation development of porcine SCNT embryo by endoplasmic reticulum stress inhibition

Lin, Tao; Lee, Jae Eun; Oqani, Reza K.; Kim, So Yeon; Cho, Eun Seok; Jeong, Yong Dae; Baek, Jun Jong; Jin, Dong Il

doi:10.1016/j.repbio.2016.10.003

Cited by 39 publications

(34 citation statements)

References 31 publications

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“…However, the GSH level of the Poor+Mela group was significantly lower than that of the Good group (Figure c). Melatonin‐scavenged ROS was further investigated in the presence and absence of the ROS inducer (Lim, Heo, & Kim, ; Lin, Lee et al, ), TM (tunicamycin). As expected, treatment of porcine oocytes with TM sharply increased the ROS level, whereas melatonin supplementation (TM+Mela) significantly reduced the TM‐induced formation of ROS (Figure d,e).…”

Section: Resultsmentioning

confidence: 99%

“…To further determine the ability of melatonin to scavenge ROS, we pre‐treated porcine oocytes with TM (tunicamycin), which reportedly increases ROS generation (Lim et al, ; Lin, Lee et al, ), and then treated the oocytes with melatonin during extended IVM. TM pre‐treatment triggered an increase in the ROS level, but this effect was rescued by melatonin supplementation.…”

Section: Discussionmentioning

confidence: 99%

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Melatonin supplementation during prolonged in vitro maturation improves the quality and development of poor‐quality porcine oocytes via anti‐oxidative and anti‐apoptotic effects

Lin

Lee

Kang

et al. 2018

Molecular Reproduction Devel

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Poor-quality oocytes (those with 1-2 layers of cumulus cells) typically possess low meiotic competence and development. Prolonging the duration of in vitro maturation (IVM; 52 hr) can enhance the maturation rate of poor-quality oocytes, but it does not improve subsequent embryonic development. This likely reflects the increased reactive oxygen species (ROS) production and apoptosis seen in these oocytes compared with the non-prolonged IVM (44 hr) group. Melatonin is a free radical scavenger, anti-oxidant and anti-apoptotic agent that reported to enhance the quality of embryos by inhibiting ROS generation and apoptosis. Therefore, we herein investigated whether melatonin combined with prolonged IVM (52 hr) could improve the quality and development of poor-quality oocytes. We supplemented IVM and/or in vitro culture (IVC) media with various concentrations (0, 10 , 10 , 10 M) of melatonin, and estimated parameters related to oocyte quality and development. The addition of melatonin (10 M) to a prolonged IVM system improved the oocyte quality and development compared with those of the melatonin-free poor-quality oocytes group, and that this was due to decreases in ROS generation, apoptosis, and DNA damage. When melatonin was added during both IVM (10 M) and IVC (10 M), we observed a cumulative positive influence on the embryonic development and quality; this treatment enhanced the expression level of Oct4 and decreased the levels of ROS, DNA damage, and apoptosis. Together, these findings suggest that the combination of melatonin plus prolonged IVM can improve the quality and development of poor-quality porcine oocytes via anti-oxidative and anti-apoptotic effects.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Melatonin supplementation during prolonged in vitro maturation improves the quality and development of poor‐quality porcine oocytes via anti‐oxidative and anti‐apoptotic effects

Lin

Lee

Kang

et al. 2018

Molecular Reproduction Devel

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“…In this study, we found increased UPR activity, an ER stress coping response, as revealed by increased XBP1s and GRP78 mRNA abundance and GRP78 immunofluorescence, in untreated late-cleaving embryos. Remarkably, treatment with TUDCA[ 44 ] which has been shown to decrease ER stress in embryos and increase blastocyst rates[ 29 , 30 , 33 , 45 ], rescued development and quality of late-cleaving embryos. TUDCA treatment had no apparent negative impacts on early-cleaving embryos.…”

Section: Discussionmentioning

confidence: 99%

Relief of endoplasmic reticulum stress enhances DNA damage repair and improves development of pre-implantation embryos

et al. 2017

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Early-cleaving embryos are known to have better capacity to reach the blastocyst stage and produce better quality embryos compared to late-cleaving embryos. To investigate the significance of endoplasmic reticulum (ER) stress on early embryo cleavage kinetics and development, porcine embryos produced in vitro were separated into early- and late-cleaving groups and then cultured in the absence or presence of the ER stress inhibitor tauroursodeoxycholic acid (TUDCA). Developing embryos were collected at days 3 to 7 of culture for assessment of ER stress status, incidence of DNA double-strand breaks (DSBs), development and total cell number. In the absence of TUDCA treatment, late-cleaving embryos exhibited ER stress, higher incidence of DNA DSBs, as well as reductions in development to the blastocyst stage and total embryo cell numbers. Treatment of late-cleaving embryos with TUDCA mitigated these effects and markedly improved embryo quality and development. These results demonstrate the importance of stress coping responses in early developing embryos, and that reduction of ER stress is a potential means to improve embryo quality and developmental competence.

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“…For altering the epigenetic status, researchers have used histone deacetylase inhibitors (HDACi) such as trichostatin A (TSA) [117,118], valproic acid (VPA) [119][120][121], scriptaid [122][123][124], LBH589 (panobinostat) [125], oxamflatin [126], PXD101 (belinostat) [127], quisinostat [128], MGCD0103 [129], or histone methyltransferase inhibitors such as MM-102 [130]. Lin et al [131] employed tauroursodeoxycholic acid (TUDCA), an inhibitor of endoplasmic reticulum (ER) stress, and demonstrated that TUDCA can enhance the developmental potential of porcine SCNT embryos by attenuating ER stress and reducing apoptosis. Wang et al [132] demonstrated that administration of siRNA or microRNA-148a, both of which can suppress the function of DNA methyltransferase 1 (DNMT1) at a transcriptional level, is effective for enhancing the developmental potential of SCNT embryos.…”

Section: Scntmentioning

confidence: 99%

Recent Advance in Genome Editing-Based Gene Modification in Pigs

Miyoshi¹,

Kawaguchi²,

Inada³

et al. 2020

Reproductive Biology and Technology in Animals

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Recently, a series of genome editing technologies including ZFNs, TALENs, and CRISPR/Cas9 systems have enabled gene modification in the endogenous target genes of various organisms including pigs, which are important for agricultural and biomedical research. Owing to its simple application for gene knockout and ease of use, the CRISPR/Cas9 is now in common use worldwide. The most important aspect of this process is the selection of the method used to deliver genome editing components to embryos. In earlier stages, zygote microinjection of these components [single guide RNA (sgRNA) + DNA/mRNA for Cas9] into the cytoplasm and/ or nuclei of a zygote has been frequently employed. However, this method is always associated with the generation of mosaic embryos in which genome-edited and unedited cells are mixed together. To avoid this mosaic issue, in vitro electroporation of zygotes in the presence of sgRNA mixed with Cas9 protein, referred to as a ribonucleoprotein (RNP), is now in frequent use. This review provides a historical background of the production of genome-edited pigs and also presents current research concerning how genome editing is induced in somatic cell nuclear transferderived embryos that have been reconstituted with normal nuclei. GE piglets have been produced using SCNT of genome-edited cells, or direct microinjection of genome-editing components (including engineered endonucleases) into the cytoplasm of zygotes, as described below in more detail. Background of second-generation genome editingAs mentioned above, site-specific engineered nucleases are used in these genome-editing techniques. ZFNs, TALENs, and CRISPR/Cas9 can all bind to DNA and induce DSB, which triggers endogenous DNA repair. If the template DNA is absent, the DSB is repaired via the NHEJ pathway where insertion or deletion of nucleotides (hereinafter called "indels") can happen in the cleaved area. These indels often cause frameshift of the amino acid sequence, leading to the generation of abnormal proteins or formation of a premature stop codon leading to cessation of protein synthesis. If template DNA homologous to the target site is present, it is inserted into the cleaved area via a site-specific HR event which is called HDR. Generally, NHEJ occurs in cells independent of its cell cycle, but HDR occurs primarily in dividing cells [30].The ZFN technique uses the ZF protein (which binds to the target DNA) and the endonuclease Fok I (which cleaves DNA) [31]. ZF protein has several protein motifs capable of recognizing specific sequences of three nucleotides and binding to them. Notably, Urnov et al. [32] first demonstrated that ZFN is effective to induce DNA editing at the endogenous target gene in mammalian cells. Its targeting efficiency was over 18% in the absence of drug selection, which is ~1000-fold higher than that achieved by traditional gene targeting.The TALEN technique uses proteins, termed transcription activator-like effectors (TALEs), which contain 33-35 amino acid repeats that flank a central DNA binding region (a...

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Tauroursodeoxycholic acid improves pre-implantation development of porcine SCNT embryo by endoplasmic reticulum stress inhibition

Cited by 39 publications

References 31 publications

Melatonin supplementation during prolonged in vitro maturation improves the quality and development of poor‐quality porcine oocytes via anti‐oxidative and anti‐apoptotic effects

Melatonin supplementation during prolonged in vitro maturation improves the quality and development of poor‐quality porcine oocytes via anti‐oxidative and anti‐apoptotic effects

Relief of endoplasmic reticulum stress enhances DNA damage repair and improves development of pre-implantation embryos

Recent Advance in Genome Editing-Based Gene Modification in Pigs

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