Study reveals how babies born from 3 parents are surprisingly similar to normal babies

In 2016, a team of doctors led by scientist John Jin Zhang claimed to have helped a woman give birth to the world’s first three-parent baby (a child that has three biological parents) using a technique called mitochondrial replacement therapy (MRT). The news soon became controversial as MRT is prohibited by law in most countries, including the U.S.

Now a group of scientists in China has conducted a study that demonstrates that spindle transfer (the MRT technique that led to the birth of the first three-parent baby) is safe and does not affect early embryonic development. One of the study's authors, Dr. Wei Shang, told Nature, “Mitochondrial replacement therapy is a controversial field. With our research, we hope to provide a foundation for the development of the technique.”

MRT and the birth of the first baby having three parents

A three-parent baby contains genetic material from three different individuals. The woman that gave birth to the first such baby was carrying genes of Leigh syndrome, a rare neurological disorder resulting from mutations in the mother’s mitochondrial DNA. A child suffering from the syndrome does not live longer than three years.

After losing two kids because of Leigh syndrome, the women approached Zhang and his team in New York. Zhang was aware that by using MRT he could prevent the occurrence of the syndrome in the next generation, but he couldn’t perform the therapy in the U.S. So they went to Mexico and the baby was born there.

Zhang and his team separated the mutated mitochondria from the DNA in the mother’s egg and then transferred the mother’s DNA to an egg they obtained from a female donor that contained normal healthy mitochondria. The modified egg from the donor was then fertilized with the father’s sperm in a test tube. This is how the resultant embryo incorporated genetic material from three parents — the mother, the father, and the female donor.

The above-mentioned type of mitochondrial-replacement therapy is called spindle transfer and although MRT is an effective technique to prevent the transfer of disease-causing genes from parents to kids. the method involves the introduction of foreign genetic material into the embryo. Therefore, it is considered unsafe, unethical, and often cited as an attempt to produce designer babies.

Does spindle transfer alter the way an embryo develops?

The researchers at the PLA general hospital studied normal embryos and embryos formed after spindle transfer for a week. More specifically, they compared blastocyst, the stage of embryonic development that generally takes place five days after an egg is fertilized. In both types of blastocysts, the rate of transcription (copying of information from DNA to mRNA) was almost the same.

Highlighting the similarities between gene expression levels in both normal and spindle transfer (ST) embryos, the researchers note in the paper, “we analyzed the differentially expressed genes (DEGs). The patterns of gene expression were nearly identical for all of the TE, EPI, and PE lineages between the ST and control embryos.”

The researchers analyzed the blastocyst stage in not just a few but over a dozen regular and ST embryos, and they didn’t notice any difference between them. Neither did they come across any factors that posed a risk to the health of the ST embryo. The researchers claim to have made the first detailed comparison of the two types of human embryos.

Stem cell expert and professor at Columbia University, Dietrich Egli believes that the comparison holds great importance since it analyzes the safety of spindle transfer embryos in depth. He suggests these findings could prove to be useful for authorities in analyzing the efficiency and safety of MRT.

However, the Chinese researchers have only taken the blastocyst stage into account, and therefore further research is required to understand the influence of ST on other embryonic development stages in humans.

The study is published in the journal PLOS Biology.

Abstract:

Mitochondrial DNA (mtDNA) mutations are often associated with incurable diseases and lead to detectable pathogenic variants in 1 out of 200 babies. Uncoupling of the inheritance of mtDNA and the nuclear genome by spindle transfer (ST) can potentially prevent the transmission of mtDNA mutations from mother to offspring. However, no well-established studies have critically assessed the safety of this technique. Here, using single-cell triple omics sequencing method, we systematically analyzed the genome (copy number variation), DNA methylome, and transcriptome of ST and control blastocysts. The results showed that, compared to that in control embryos, the percentage of aneuploid cells in ST embryos did not significantly change. The epiblast, primitive endoderm, and trophectoderm (TE) of ST blastocysts presented RNA expression profiles that were comparable to those of control blastocysts. However, the DNA demethylation process in TE cells of ST blastocysts was slightly slower than that in the control blastocysts. Collectively, our results suggest that ST seems generally safe for embryonic development, with a relatively minor delay in the DNA demethylation process at the blastocyst stage.