31 August 2022

Is it safe

The technology of a child from three parents was called safe for the embryo genome

Irina Grishchenko, N+1

Geneticists tested the safety of transferring the spindle of division of one egg into another before fertilization and called such a transfer safe. They received embryos from control and experimental eggs. After that, the scientists studied the genetic and functional differences in the embryos. The study is published in the journal PLoS Biology (Qi et al., Single-cell multiomics analyses of spindle-transferred human embryos suggest a mostly normal embryonic development).

Mitochondria — organelles-energy stations: they form ATP molecules for all vital processes inside the cell. Unlike other organelles, they have their own DNA. Sometimes mutations occur in mitochondrial DNA that can cause hereditary diseases such as Kerns-Sayre syndrome, MELAS syndrome, hereditary Leber optic neuropathy, etc. According to scientists, every 200 children are born with pathologies in the mitochondria that can lead to diseases.

When transmitted between generations, only maternal mitochondria are inherited. To prevent the inheritance of mutant mitochondria during IVF, scientists are developing a technology for transferring DNA from an egg with defective organelles to a healthy oocyte with removed genetic material. The transfer occurs either immediately after fertilization (pronuclear transfer), or before it (transfer of the division spindle). The mitochondrial transfer procedure was performed as an experimental therapy only in some countries (China, USA, Mexico). In other states, it is not officially allowed because there is no complete confidence in the safety of this technology. To make sure that such a transfer does not harm the development of the embryo, the technology of children from three parents was tested on primates. Another method of verification is based on a genome-wide analysis of human blastocyst cells after fertilization of an experimental egg in the laboratory.

A group of scientists from Peking University and General Hospital Medical Center in In Beijing, under the leadership of Wei Shang and Fuzhou Tang, three different types of analysis based on single cell sequencing were performed: genome copy number analysis, DNA methylation level and transcriptome. The researchers studied individual cells from 23 blastocysts after spindle transfer and compared them with 23 control blastocysts obtained by IVF.

The researchers found no differences in the number of DNA copies in cells, an indicator of genome integrity, between experimental and control blastocysts. The RNA expression profiles also turned out to be similar, regardless of which layer of the blastocyst the analyzed cells originated from.

The authors found a small but significant decrease in the level of DNA demethylation in one layer of blastocyst cells — trophoectoderm — in spindle-transferred oocytes. DNA demethylation is necessary during development to increase gene expression. But the detected decrease in demethylation indicates a slight delay in gene activation, and not a complete violation of this process, since there were no violations in other layers of the blastocyst.

The researchers believe that the results obtained will stimulate the further introduction of spindle transfer for IVF when there is a risk of mitochondrial disease. So far, the technology of children from three parents is the only way to save a child from mitochondrial pathologies.

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