A recent study published in the journal Nature Genetics sheds light on the bedrock scientific principle that mitochondrial DNA (mtDNA) is exclusively passed down by the mother. Previously, it was believed that paternal mtDNA was eliminated after fertilization, but this study found that mature sperm lack intact mtDNA.
Researchers from Oregon Health & Science University and other institutions discovered that while sperm cells do carry a small number of mitochondria, they do not contain mtDNA. The sperm also lacked a protein essential for mtDNA maintenance, known as mitochondrial transcription factor A (TFAM).
The reason why sperm are not allowed to contribute mtDNA remains unclear, but one theory is that sperm use a significant amount of mitochondrial energy during fertilization, which could lead to the accumulation of mutations in mtDNA. In contrast, developing eggs known as oocytes primarily obtain energy from surrounding cells, thus maintaining relatively pristine mtDNA.
The study emphasizes the importance of maternal mtDNA contribution in conferring an evolutionary advantage by limiting the risk of mtDNA mutations that cause diseases in offspring. Mutations in mtDNA can lead to potentially fatal disorders in organs with high-energy demands.
To address the transmission of known mtDNA disorders, the study’s corresponding author, Shoukhrat Mitalipov, has pioneered a method called mitochondrial replacement therapy. This technique replaces mutant mtDNA with healthy mtDNA from donor eggs through in vitro fertilization.
While clinical trials using this procedure have been limited in the United States, they are being conducted overseas to prevent disease and treat infertility.
The researchers believe that understanding the role of TFAM during sperm maturation and fertilization could hold the key to treating certain infertility disorders and improving the efficiency of assisted reproductive technologies.
This study provides valuable insights into the mechanism of maternal inheritance of mtDNA and its implications for human fertility and germ cell therapy.
Lee, W., et al. (2023) Molecular basis for maternal inheritance of human mitochondrial DNA. Nature Genetics. doi.org/10.1038/s41588-023-01505-9.