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Embryo manipulation via assisted reproductive technology and epigenetic asymmetry in mammalian early development.

Kohda T, Ishino F - Philos. Trans. R. Soc. Lond., B, Biol. Sci. (2013)

Bottom Line: The sperm and egg DNA methylation profiles are very different from each other, and just after fertilization, only the paternally derived genome is subjected to genome-wide hydroxylation of 5-methylcytosine, resulting in an epigenetic asymmetry in parentally derived genomes.Zygotic gene activation from paternally or maternally derived genomes also starts around the two-cell stage, presumably in a different manner in each of them.In particular, we focus on the effects of intracytoplasmic sperm injection that can result in long-lasting transcriptome disturbances, at least in mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.

ABSTRACT
The early stage of mammalian development from fertilization to implantation is a period when global and differential changes in the epigenetic landscape occur in paternally and maternally derived genomes, respectively. The sperm and egg DNA methylation profiles are very different from each other, and just after fertilization, only the paternally derived genome is subjected to genome-wide hydroxylation of 5-methylcytosine, resulting in an epigenetic asymmetry in parentally derived genomes. Although most of these differences are not present by the blastocyst stage, presumably due to passive demethylation, the maintenance of genomic imprinting memory and X chromosome inactivation in this stage are of critical importance for post-implantation development. Zygotic gene activation from paternally or maternally derived genomes also starts around the two-cell stage, presumably in a different manner in each of them. It is during this period that embryo manipulation, including assisted reproductive technology, is normally performed; so it is critically important to determine whether embryo manipulation procedures increase developmental risks by disturbing subsequent gene expression during the embryonic and/or neonatal development stages. In this review, we discuss the effects of various embryo manipulation procedures applied at the fertilization stage in relation to the epigenetic asymmetry in pre-implantation development. In particular, we focus on the effects of intracytoplasmic sperm injection that can result in long-lasting transcriptome disturbances, at least in mice.

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Principal component analysis of the gene expression profile. The transcriptional profiles are shown of the neonatal brain of mice conceived by ICSI, IVF or natural mating (NM) and embryo transfer to the surrogate mothers. Vertical axis (PCA1) and horizontal axis (PCA2) are principal component 1 and 2, respectively, of the gene expression profiles obtained by DNA microarray. Genetic background of all neonates are B6×D2. Strain name of surrogate mothers (B6 or ICR) are indicated in parentheses. NM: natural mating and continued the pregnancy. NM (B6): natural mating, flush out embryos and transplant to B6 surrogate mothers. NM (ICR); natural mating, flush out embryos and transplant to ICR surrogate mothers.
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RSTB20120353F3: Principal component analysis of the gene expression profile. The transcriptional profiles are shown of the neonatal brain of mice conceived by ICSI, IVF or natural mating (NM) and embryo transfer to the surrogate mothers. Vertical axis (PCA1) and horizontal axis (PCA2) are principal component 1 and 2, respectively, of the gene expression profiles obtained by DNA microarray. Genetic background of all neonates are B6×D2. Strain name of surrogate mothers (B6 or ICR) are indicated in parentheses. NM: natural mating and continued the pregnancy. NM (B6): natural mating, flush out embryos and transplant to B6 surrogate mothers. NM (ICR); natural mating, flush out embryos and transplant to ICR surrogate mothers.

Mentions: Conventional IVF and ICSI procedures are composed of several common artificial techniques, such as super ovulation, collection of the unfertilized eggs, in vitro culture and transfer to surrogate mothers, in addition to the process of fertilization itself. For proper assessment of the effects of IVF and ICSI, it should be taken into account that other experimental procedures are carried out under the same conditions, such as the overall ex vivo embryo-handling, including the in vitro culture conditions and transplantation to the surrogate mothers. The gene expression profiles should be compared between neonates from natural mating and those conceived by conventional IVF. In our analysis, a comparison was carried out using three neonatal organs, the brain, liver and kidney. In these experiments, fertilized eggs from natural mating were collected and transplanted to surrogate mothers in the same manner as those from IVF. Embryos were cultured for one day and transferred at the two-cell stage to minimize the effect of in vitro culture. As shown in figure 3, no difference was observed between the gene expression profiles of these two, indicating that the conventional IVF technique itself is a safe method, at least under the limited in vitro culture condition of a single day. The only differences we observed were dependent on the strains of the true or surrogate mothers.Figure 3.


Embryo manipulation via assisted reproductive technology and epigenetic asymmetry in mammalian early development.

Kohda T, Ishino F - Philos. Trans. R. Soc. Lond., B, Biol. Sci. (2013)

Principal component analysis of the gene expression profile. The transcriptional profiles are shown of the neonatal brain of mice conceived by ICSI, IVF or natural mating (NM) and embryo transfer to the surrogate mothers. Vertical axis (PCA1) and horizontal axis (PCA2) are principal component 1 and 2, respectively, of the gene expression profiles obtained by DNA microarray. Genetic background of all neonates are B6×D2. Strain name of surrogate mothers (B6 or ICR) are indicated in parentheses. NM: natural mating and continued the pregnancy. NM (B6): natural mating, flush out embryos and transplant to B6 surrogate mothers. NM (ICR); natural mating, flush out embryos and transplant to ICR surrogate mothers.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539368&req=5

RSTB20120353F3: Principal component analysis of the gene expression profile. The transcriptional profiles are shown of the neonatal brain of mice conceived by ICSI, IVF or natural mating (NM) and embryo transfer to the surrogate mothers. Vertical axis (PCA1) and horizontal axis (PCA2) are principal component 1 and 2, respectively, of the gene expression profiles obtained by DNA microarray. Genetic background of all neonates are B6×D2. Strain name of surrogate mothers (B6 or ICR) are indicated in parentheses. NM: natural mating and continued the pregnancy. NM (B6): natural mating, flush out embryos and transplant to B6 surrogate mothers. NM (ICR); natural mating, flush out embryos and transplant to ICR surrogate mothers.
Mentions: Conventional IVF and ICSI procedures are composed of several common artificial techniques, such as super ovulation, collection of the unfertilized eggs, in vitro culture and transfer to surrogate mothers, in addition to the process of fertilization itself. For proper assessment of the effects of IVF and ICSI, it should be taken into account that other experimental procedures are carried out under the same conditions, such as the overall ex vivo embryo-handling, including the in vitro culture conditions and transplantation to the surrogate mothers. The gene expression profiles should be compared between neonates from natural mating and those conceived by conventional IVF. In our analysis, a comparison was carried out using three neonatal organs, the brain, liver and kidney. In these experiments, fertilized eggs from natural mating were collected and transplanted to surrogate mothers in the same manner as those from IVF. Embryos were cultured for one day and transferred at the two-cell stage to minimize the effect of in vitro culture. As shown in figure 3, no difference was observed between the gene expression profiles of these two, indicating that the conventional IVF technique itself is a safe method, at least under the limited in vitro culture condition of a single day. The only differences we observed were dependent on the strains of the true or surrogate mothers.Figure 3.

Bottom Line: The sperm and egg DNA methylation profiles are very different from each other, and just after fertilization, only the paternally derived genome is subjected to genome-wide hydroxylation of 5-methylcytosine, resulting in an epigenetic asymmetry in parentally derived genomes.Zygotic gene activation from paternally or maternally derived genomes also starts around the two-cell stage, presumably in a different manner in each of them.In particular, we focus on the effects of intracytoplasmic sperm injection that can result in long-lasting transcriptome disturbances, at least in mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.

ABSTRACT
The early stage of mammalian development from fertilization to implantation is a period when global and differential changes in the epigenetic landscape occur in paternally and maternally derived genomes, respectively. The sperm and egg DNA methylation profiles are very different from each other, and just after fertilization, only the paternally derived genome is subjected to genome-wide hydroxylation of 5-methylcytosine, resulting in an epigenetic asymmetry in parentally derived genomes. Although most of these differences are not present by the blastocyst stage, presumably due to passive demethylation, the maintenance of genomic imprinting memory and X chromosome inactivation in this stage are of critical importance for post-implantation development. Zygotic gene activation from paternally or maternally derived genomes also starts around the two-cell stage, presumably in a different manner in each of them. It is during this period that embryo manipulation, including assisted reproductive technology, is normally performed; so it is critically important to determine whether embryo manipulation procedures increase developmental risks by disturbing subsequent gene expression during the embryonic and/or neonatal development stages. In this review, we discuss the effects of various embryo manipulation procedures applied at the fertilization stage in relation to the epigenetic asymmetry in pre-implantation development. In particular, we focus on the effects of intracytoplasmic sperm injection that can result in long-lasting transcriptome disturbances, at least in mice.

Show MeSH
Related in: MedlinePlus