Early epigenetic reprogramming in fertilized, cloned, and parthenogenetic embryos

Sepulveda-Rincon, Lessly P.; Solanas, Edgar del Llano; Serrano-Revuelta, Elisa; Ruddick, Lydia; Maalouf, Walid E.; Beaujean, Nathalie

doi:10.1016/j.theriogenology.2016.04.022

Cited by 31 publications

(22 citation statements)

References 99 publications

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“…Generally, incomplete DNA methylation reprogramming induced by SCNT can be due to the repressive factors present in donor cells [6]. Here, our results demonstrated that Dnmt1s in donor cells serves as a critical barrier for ZGA and genomic methylation reprogramming, leading to the developmental arrest of SCNT embryos, and removal of this barrier by siRNA enhances DNA methylation reprogramming, allows the efficient activation of genes required for embryonic development, and thus improves the SCNT efficiency (Figure 6).…”

Section: Discussionsupporting

confidence: 52%

“…However, to date, the cloning efficiency remains low, limiting SCNT-associated research and application [4–6]. …”

Section: Introductionmentioning

confidence: 99%

“…Generally, it is thought that the incomplete DNA methylation reprogramming in SCNT embryos can be due to that tissue specific genes in donor cells sustain their fate against nuclear reprogramming induced by oocyte factors [6]. Presently, certain repressive factors, such as Dnmt1, Dnmt3L and H3K9me3, have been identified, but the regulatory mechanism is not well clarified in SCNT embryos [10–12].…”

Section: Introductionmentioning

confidence: 99%

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Dnmt1s in donor cells is a barrier to SCNT-mediated DNA methylation reprogramming in pigs

Song

et al. 2017

Oncotarget

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Low development of somatic cell nuclear transfer embryos could be due to the incomplete DNA methylation reprogramming, and Dnmt1s existing in donor cells may be one cause of this disrupted DNA methylation reprogramming. However, the reprogramming pattern of Dnmt1s and its effect on DNA methylation reprogramming in cloned embryos remain poorly understood. Here, we displayed that along with the significantly higher Dnmt1 expression at the zygotic gene activation stage of cloned embryos, genomic methylation level was markedly upregulated, and the arrested rate was significantly higher compared with their in vitro fertilization counterparts. Then, we demonstrated that Dnmt1s, not Dnmt1o, methylation and expression levels in cloned embryos were significantly higher from the 1-cell to 4-cell stage but markedly lower at the blastocyst stage. When Dnmt1s in donor cells was appropriately removed, more cloned embryos passed through the zygotic gene activation stage and the blastocyst rate significantly increased. Furthermore, Dnmt1s knockdown significantly improved itself and genomic methylation reconstruction in cloned embryos. Finally, we found that Dnmt1s removal significantly promoted the demethylation and expression of pluripotent genes in cloned embryos. Taken together, these data suggest that Dnmt1s in donor cells is a critical barrier to somatic cell nuclear transfer mediated DNA methylation reprogramming, impairing the development of cloned embryos.

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Section: Discussionsupporting

confidence: 52%

“…However, to date, the cloning efficiency remains low, limiting SCNT-associated research and application [4–6]. …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dnmt1s in donor cells is a barrier to SCNT-mediated DNA methylation reprogramming in pigs

Song

et al. 2017

Oncotarget

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“…Uniparental embryos are an effective tool to explore genetic effects on the process of maternal and paternal genomic imprinting, as well as the contribution of the maternal and paternal genome in early embryonic development (Latham, Kutyna & Wang, 1999; Kono et al, 2004; Gebert et al, 2009; Sepulveda-Rincon et al, 2016; Ogawa et al, 2009). Some studies report that the addition of granulocyte colony-stimulating factor and valproic acid, AY9944A-7 and histone deacetylase inhibitor in the IVM medium improve the viability of parthenogenetic embryos in porcine (Cai et al, 2015; Huang et al, 2015), sheep (Hao et al, 2015) and androgenetic embryos in bovine (Zhang et al, 2014), respectively.…”

Section: Introductionmentioning

confidence: 99%

The effects of melatonin on bovine uniparental embryos developmentin vitroand the hormone secretion of COCs

Wang

Bao-ru

Liu

et al. 2017

PeerJ

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Melatonin is a unique multifunctional molecule that mediates reproductive functions in animals. In this study, we investigated the effects of melatonin on bovine parthenogenetic and androgenetic embryonic development, oocyte maturation, the reactive oxygen species (ROS) levels in parthenogenetic and androgenetic embryos and cumulus—oocyte complexes (COCs) hormone secretion with melatonin supplementation at four concentrations (0, 10, 20, and 30 pmol/mL), respectively. The results showed that melatonin significantly promoted the rates of bovine parthenogenetic and androgenetic embryonic cleavage and morula and blastocysts development (P < 0.05). The rate of cleavage was higher in the androgenetic embryo than that in the parthenogenetic embryo. Compared with the parthenogenetic embryos, the androgenetic embryos had a poor developmental competence from morula to blastocyst stage. Moreover, the levels of ROS were significantly lower in the parthenogenetic and androgenetic embryoes with melatonin-treated group than that of the control group (P < 0.05). Melatonin supplemented significantly increased the maturation rate of oocyte in vitro (P < 0.05). More importantly, melatonin significantly promoted the secretion of progesterone and estradiol by COCs (P < 0.05). To reveal the regulatory mechanism of melatonin on steroids synthesis, we found that steroidogenic genes (CYP11A1, CYP19A1 and StAR) were upregulated, suggesting that melatonin regulated estradiol and progesterone secretion through mediating the expression of steroidogenic genes (CYP11A1, CYP19A1 and StAR). In addition, MT1 and MT2 were identified in bovine early parthenogenetic and androgenetic embryos using western blot. It could be concluded that melatonin had beneficial effects on bovine oocyte in vitro maturation, COC hormone secretion, early development of subsequent parthenogenetic and androgenetic embryos. It is inferred that melatonin could be used to enhance the efficiency of in vitro developed embryos.

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“…This rate greatly limits the widespread application of nuclear transfer technology. The low developmental efficiency of SCNT embryos is mainly attributed to the incomplete reprogramming of the donor cell’s nuclear genome during preimplantation embryo development [5]. …”

Section: Introductionmentioning

confidence: 99%

DOT1L inhibitor improves early development of porcine somatic cell nuclear transfer embryos

et al. 2017

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Incomplete epigenetic reprogramming of the genome of donor cells causes poor early and full-term developmental efficiency of somatic cell nuclear transfer (SCNT) embryos. Previous research indicate that inhibition of the histone H3 K79 methyltransferase DOT1L, using a selective pharmacological inhibitor EPZ004777 (EPZ), significantly improved reprogramming efficiency during the generation of mouse induced pluripotent stem cells. However, the roles of DOT1L in porcine nuclear transfer-mediated cellular reprogramming are not yet known. Here we showed that DOT1L inhibition via 0.5 nM EPZ treatment for 12 or 24 h significantly enhanced the blastocyst rate of SCNT embryos and dramatically reduced the level of H3K79me2 during SCNT 1-cell embryonic development. Additionally, H3K79me2 level in the EPZ-treated SCNT embryos was similar to that in in vitro fertilized embryos, suggesting that DOT1L-mediated H3K79me2 is a reprogramming barrier to early development of porcine SCNT embryos. qRT-PCR analysis further demonstrated that DOT1L inactivation did not change the expression levels of DOT1L itself but increased the expression levels of POU5F1, LIN28, SOX2, CDX2 and GATA4 associated with pluripotency and early cell differentiation. In conclusion, DOT1L inhibitor improved early developmental efficiency of porcine SCNT embryos probably via inducing the increased expression of genes important for pluripotency and lineage specification.

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Early epigenetic reprogramming in fertilized, cloned, and parthenogenetic embryos

Cited by 31 publications

References 99 publications

Dnmt1s in donor cells is a barrier to SCNT-mediated DNA methylation reprogramming in pigs

Dnmt1s in donor cells is a barrier to SCNT-mediated DNA methylation reprogramming in pigs

The effects of melatonin on bovine uniparental embryos developmentin vitroand the hormone secretion of COCs

DOT1L inhibitor improves early development of porcine somatic cell nuclear transfer embryos

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