Optimizing treatment of tauroursodeoxycholic acid to improve embryonic development after in vitro maturation of cumulus-free oocytes in mice

Mochizuki, Masato; Miyagi, Kazuya; Kishigami, Satoshi

doi:10.1371/journal.pone.0202962

Cited by 9 publications

(13 citation statements)

References 19 publications

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“…Similarly, Song et al (2011) reported that addition of TUDCA reduced levels of Xbp1 splicing, transcription of the ER-stress-associated gene GRP78 , which codes for ATF6 , an α-mannidose-like protein that enhances ER degradation, and blastomere apoptosis in bovine SCNT embryos. In addition, TUDCA can reduce hyperosmolar-induced ER stress and ER-stress-induced apoptosis during oocyte development, and promote embryonic development in mouse embryos (Zhang et al, 2012a; Basar et al, 2014; Mochizuki et al, 2018). In contrast to previous studies, we applied TUDCA only during micromanipulation and 3 h after fusion and activation, not during the IVC stage, to enhance the in vitro development of the SCNT embryos.…”

Section: Discussionmentioning

confidence: 99%

Effects of Endoplasmic Reticulum Stress Inhibitor Treatment during the Micromanipulation of Somatic Cell Nuclear Transfer in Porcine Oocytes

Park

Kim

et al. 2019

Dev. Reprod.

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We examined the effects of endoplasmic reticulum (ER) stress inhibitor treatment during the micromanipulation of porcine somatic cell nuclear transfer (SCNT) on the in vitro development of SCNT embryos. ER stress inhibitors such as salubrinal (200 nM) and tauroursodeoxycholic acid (TUDCA; 100 μM) were added to the micromanipulation medium and holding medium. The expression of X-box binding protein 1 ( Xbp1 ), ER-stress-associated genes, and apoptotic genes in SCNT embryos was confirmed at the one-cell and blastocyst stages. Levels of Xbp1 splicing and expression of ER-stress-associated genes in SCNT embryos at the one-cell stage decreased significantly with TUDCA treatment ( p <0.05). The expression of ER-stress-associated genes also decreased slightly with the addition of both salubrinal and TUDCA (Sal+TUD). The expression levels of caspase-3 and Bcl2-associated Xprotein ( Bax ) mRNA were also significantly lower in the TUDCA and Sal+TUD treatments ( p <0.05). At the blastocyst stage, there were no differences in levels of Xbp1 splicing, and transcription of ER-stress-associated genes and apoptosis genes between control and treatment groups. However, the blastocyst formation rate (20.2%) and mean blastocyst cell number (63.0±7.2) were significantly higher ( p <0.05) for embryos in the TUDCA treatment compared with those for control (12.6% and 41.7±3.1, respectively). These results indicate that the addition of ER-stress inhibitors, especially TUDCA, during micromanipulation can inhibit cellular damage and enhance in vitro development of SCNT embryos by reducing stress levels in the ER.

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Section: Discussionmentioning

confidence: 99%

Effects of Endoplasmic Reticulum Stress Inhibitor Treatment during the Micromanipulation of Somatic Cell Nuclear Transfer in Porcine Oocytes

Park

Kim

et al. 2019

Dev. Reprod.

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“…TUDCA is a chemical chaperone known as an ER stress inhibitor that assists protein folding and suppresses ER stress (Xie et al, 2002;Lee et al, 2010). Several studies have shown that ER stress is inhibited when TUDCA is treated to embryo or cell in culture period (Zhang et al, 2012a,b;Yoon et al, 2014;Lin et al, 2015, Mochizuki et al, 2018. In addition, our previous study showed that when TUDCA is treated during the micromanipulation and activation processes of the SCNT embryo, Xbp1s and ER stress-associated genes are significantly reduced, thereby increasing the development and quality of SCNT embryos (Park et al, 2019).…”

Section: A B C Dmentioning

confidence: 99%

Endoplasmic Reticulum (ER) Stress Inhibitor or Antioxidant Treatments during Micromanipulation Can Inhibit Both ER and Oxidative Stresses in Porcine SCNT Embryos

Park¹,

Park²,

Kim³

et al. 2020

Dev. Reprod.

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We investigated the effects of endoplasmic reticulum (ER) stress inhibitor and antioxidant treatments during the micromanipulation of somatic cell nuclear transfer (SCNT) on in vitro development of SCNT embryos. Tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor and vitamin C (Vit. C), an antioxidant, were treated by alone or in combination, then, the level of X-box binding protein 1 (Xbp1) splicing and the expressions of ER stress-associated genes, oxidative stress-related genes, and apoptotic genes were confirmed in the 1-cell and blastocyst stages. In the 1-cell stage, the levels of Xbp1 splicing were significantly decreased in TUDCA and Vit. C treatment groups compared to the control (p<0.05). In addition, the expression levels of most ER stress-associated genes and oxidative stress-related genes were significantly lower in all treatment groups than the control (p<0.05), and the transcript levels of apoptotic genes were also significantly lower in all treatment groups than the control (p<0.05). In the blastocyst stage, decreased expression of ER stress-, oxidative stress-, and apoptosis-related genes were observed only in some treatments. However, the blastocyst formation rates in TUDCA and Vit. C treatment groups (24.8% and 22.0%, respectively) and mean blastocyst cell number in all treatment groups (59.7±4.3 to 63.5±3.3) were significantly higher (p<0.05) than those of control. The results showed that the TUDCA or Vit. C treatment during micromanipulation inhibited both ER and oxidative stresses in the early stage of SCNT embryos, thereby reducing cell damage and promoting in vitro development.

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“…To relieve ER stress, ER stress inhibitors are added to the culture media. Tauroursodeoxycholic acid (TUDCA), a bile acid that acts as a potent chemical chaperone (Xie et al, 2002;Cortez and Sim, 2014), has been used to alleviate ER stress during in vitro oocyte maturation and/or embryo development (Song et al, 2011;Kim et al, 2012;Zhang et al, 2012;Yoon et al, 2014;Zhao et al, 2015;Mochizuki et al, 2018). Although the exact chaperoning mechanism of TUDCA is still unclear, it has been shown to prevent UPR malfunction and ameliorate ER stress in various cell types (Xie et al, 2002;Miller et al, 2007;Lee et al, 2010;Seyhun et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Treatment of in vitro-Matured Bovine Oocytes With Tauroursodeoxycholic Acid Modulates the Oxidative Stress Signaling Pathway

Pioltine

Costa

Latorraca

et al. 2021

Front. Cell Dev. Biol.

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In several species, oocyte and embryo competence are improved by the addition of endoplasmic reticulum (ER) stress inhibitors to in vitro maturation (IVM) medium and/or in vitro culture (IVC) medium. This study aimed to evaluate the effects of three concentrations of tauroursodeoxycholic acid (TUDCA; 50, 200, and 1,000 μM), a chemical chaperone for relieving ER stress, during IVM of bovine cumulus–oocyte complexes (COCs) for 24 h. Treated oocytes were analyzed for nuclear maturation, reactive oxygen species (ROS) production, mitochondrial activity, and abundance of target transcripts. In addition, the number of pronuclei in oocytes was evaluated after 18–20 h of insemination, and the rates of blastocyst and hatched blastocyst formation were evaluated after 7 and 8/9 days of culture, respectively. We further evaluated the transcript abundance of embryonic quality markers. Our findings showed that supplementation of IVM medium with 200 μM of TUDCA decreased ROS production and increased abundance of transcripts related to antioxidant activity in oocytes (CAT, GPX1, and HMOX1) and embryos (GPX1 and PRDX3). Interestingly, high concentration of TUDCA (1,000 μM) was toxic to oocytes, reducing the nuclear maturation rate, decreasing mitochondrial activity, and increasing the abundance of ER stress (HSPA5) and cellular apoptosis (CASP3 and CD40) related transcripts. The results of this study suggest that treatment with 200 μM of TUDCA is associated with a greater resistance to oxidative stress and indirectly with ER stress relief in bovine oocytes.

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Optimizing treatment of tauroursodeoxycholic acid to improve embryonic development after in vitro maturation of cumulus-free oocytes in mice

Cited by 9 publications

References 19 publications

Effects of Endoplasmic Reticulum Stress Inhibitor Treatment during the Micromanipulation of Somatic Cell Nuclear Transfer in Porcine Oocytes

Effects of Endoplasmic Reticulum Stress Inhibitor Treatment during the Micromanipulation of Somatic Cell Nuclear Transfer in Porcine Oocytes

Endoplasmic Reticulum (ER) Stress Inhibitor or Antioxidant Treatments during Micromanipulation Can Inhibit Both ER and Oxidative Stresses in Porcine SCNT Embryos

Treatment of in vitro-Matured Bovine Oocytes With Tauroursodeoxycholic Acid Modulates the Oxidative Stress Signaling Pathway

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