Is Spindle Transfer Safe?
A study of mitochondrial replacement through spindle transfer
Background
In 2016, a child with a combination of three people’s DNA was born. This phenomenon resulted from an innovative new technique developed to enable women with mitochondrial defects to have healthy children. Since all mitochondrial DNA is inherited from the mother, women with mitochondrial diseases will inevitably pass them on to their children. The only way to prevent this is to substitute the mother’s mitochondria with a female donor’s mitochondria prior to fertilization and embryo development. A child that develops from such an embryo will possess the nuclear DNA of its biological mother and father and the mitochondrial DNA of the donor (known as its “biological mitochondrial mother”).
Mitochondrial defects in children are almost as common as childhood cancer, affecting approximately 1 in 5,000 children. As every biology student knows, the mitochondria are the powerhouses of the cell. Their role is to create ATP, the energy currency of the cell, to power virtually all cellular processes. When the mitochondria do not function properly, less energy is produced, resulting in organ dysfunction. This can produce a variety of devastating diseases, affecting every body system. Mitochondrial replacement therapy appears to be the best mechanism for preventing the transmission of mitochondrial diseases from a mother to her offspring.
Mitochondrial replacement therapy is a procedure performed prior to in-vitro fertilization (IVF) that works by replacing abnormal mitochondria in a woman’s egg with the healthy mitochondria of a donor egg. There are multiple methods by which this can be done; however, a technique known as spindle transfer resulted in the baby that was born with a mix of three people’s DNA. Spindle transfer works by transferring the nuclear DNA of the biological mother into a donor egg with healthy mitochondria, which has had its nucleus removed. The result is an egg with maternal DNA and donor mitochondria that can subsequently be fertilized by sperm.
Summary
After the initial, controversial usage of this technique, concerns surrounding its safety were raised. A team of scientists investigated this question of safety by studying the effects of this technique on embryos. IVF already comes with an inherent number of risks; this study sought to determine what risks were increased specifically through the usage of spindle transfer on embryos.
To evaluate the safety of this technique, researchers compared dozens of human embryos that had undergone spindle transfer to a control group of normal embryos. One week after spindle transfer and egg fertilization, the levels of gene expression and transcription were measured in both groups. These measurements showed that the two groups essentially mirror each other in development, with almost identical levels of gene expression and transcription at the blastocyst (five-day-old) stage.
This study appears to indicate that spindle transfer has little effect on early embryonic development. The control embryos experienced similar rates of chromosome abnormalities to the spindle transfer embryos, demonstrating that spindle transfer does not lead to increased rates of major chromosomal abnormalities.
This is a significant positive finding because chromosomal abnormalities cause approximately 50% of first-trimester miscarriages. While chromosome abnormalities are often not viable, some abnormalities can be but can cause the death of the infant soon after birth or abnormalities throughout life.
The control embryos experienced similar rates of chromosome abnormalities to the spindle transfer embryos, demonstrating that spindle transfer does not lead to increased rates of major chromosomal abnormalities.
The only distinction found between the control embryos and the embryos on which spindle transfer was performed was the rate of DNA demethylation. In the spindle-transfer embryos, the rate of DNA methylation was slightly slower.
This could potentially lead to epigenetic changes in DNA expression, meaning that the proteins expressed by the DNA could be slightly different in nature without the DNA being physically changed through mutation. The extent of difference in the expression of these traits between control embryos and spindle-transfer embryos, however, remains unknown.
If future studies show that spindle transfer does not increase the risk of chromosomal abnormalities later in embryonic development (past the blastocyst stage) or cause different expression by proteins, this method of mitochondrial replacement therapy will likely become a commonplace technique in fertility medicine.
