Recent research has shed light on a fundamental scientific principle concerning mitochondrial DNA (mtDNA), the distinct genetic code found within the cellular organelle that powers every cell in the body. This genetic material is exclusively inherited from the mother.
The collaborative study involving Oregon Health & Science University and other research institutions, published in Nature Genetics, affirms the longstanding understanding that mtDNA in humans is solely transmitted through egg cells. In other words, only the mother contributes the genetic code carried by the numerous mitochondria crucial for cellular energy production throughout the body.
Previously, it was believed that paternal mtDNA was eliminated shortly after a sperm fused with an egg during fertilization, likely through a mechanism resembling an immune response.
However, the study has revealed that while mature sperm do carry a small number of mitochondria, they lack intact mtDNA. Co-author Shoukhrat Mitalipov, Ph.D., the director of the Center for Embryonic Cell and Gene Therapy at OHSU, stated, “We found that each sperm cell does bring about 100 mitochondria as organelles when it fertilizes an egg, but these mitochondria do not contain mtDNA.”
Moreover, the study found that sperm cells not only lack intact mtDNA but also lack a crucial protein for mtDNA maintenance called mitochondrial transcription factor A (TFAM). The reasons for this exclusion of mtDNA from sperm remain unclear, though Mitalipov theorizes that it may be linked to the significant mitochondrial energy used by sperm during fertilization, potentially leading to an accumulation of mtDNA mutations. In contrast, developing eggs, or oocytes, primarily draw energy from surrounding cells, maintaining relatively pristine mtDNA.
The study emphasizes that eggs exclusively pass on high-quality mtDNA, partly because they do not utilize mitochondria as an energy source. While sperm carry around 100 mitochondria, they are vastly outnumbered by the hundreds of thousands of mitochondria present in each egg cell, each containing the 37 genes of mitochondrial DNA. This maternal contribution of mtDNA is believed to provide an evolutionary advantage by reducing the risk of mtDNA mutations that can cause disease in offspring.
Mitochondria play a critical role in cellular respiration and energy production throughout the body. Mutations in mtDNA can lead to potentially fatal disorders affecting organs with high-energy demands, such as the heart, muscles, and brain.
To prevent the transmission of known mtDNA disorders from mothers to their children, Mitalipov pioneered a technique called mitochondrial replacement therapy. This approach involves replacing mutant mtDNA through in vitro fertilization using healthy mtDNA from donor eggs. Clinical trials for this procedure are being conducted overseas due to restrictions in the United States.
The researchers note that this new discovery holds significant implications for human fertility and germ cell therapy. Understanding the role of TFAM in sperm maturation and its function during fertilization could potentially offer insights into treating specific infertility disorders and enhancing the effectiveness of assisted reproductive technologies. Corresponding author Dmitry Temiakov, Ph.D., a molecular biologist at Thomas Jefferson University in Philadelphia, emphasizes the potential impact of understanding TFAM’s role in these processes.