A recent study published in the journal Nature Genetics sheds light on the fundamental scientific principle that mitochondrial DNA (mtDNA) is exclusively transmitted through the maternal line. Previously, it was believed that paternal mtDNA was eliminated after fertilization, but this study discovered that mature spermatozoa lack intact mtDNA.
Researchers from the University of Science and Health of Oregon and other institutions discovered that while sperm cells carry a small amount of mitochondria, they do not contain mtDNA. It was also found that spermatozoa lack an essential protein for mtDNA maintenance called Mitochondrial Transcription Factor A (TFAM).
Although the exact reason why spermatozoa do not contribute mtDNA is not known, one theory suggests that they use a significant amount of mitochondrial energy during fertilization, which could lead to the accumulation of mtDNA mutations. On the other hand, developing eggs, known as oocytes, primarily obtain energy from surrounding cells, allowing for relatively intact mtDNA.
This study highlights the importance of maternal contribution of mtDNA in conferring an evolutionary advantage by limiting the risk of mtDNA mutations that cause diseases in offspring. Mutations in mtDNA can lead to potentially life-threatening disorders in organs with high energy demands.
To address the transmission of known mtDNA disorders, the corresponding author of the study, Shoukhrat Mitalipov, has developed a method called mitochondrial replacement therapy. This technique replaces mutant mtDNA with healthy mtDNA from donor eggs through in vitro fertilization.
While clinical trials utilizing this procedure have been limited in the United States, they are being conducted in other countries to prevent diseases and treat infertility.
Researchers believe that understanding the role of TFAM during sperm maturation and fertilization could be key to treating certain infertility disorders and improving the effectiveness 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-line 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.