News | Why Is Mitochondrial DNA Inherited Only from the Mother? New Research Identifies a Key Reason
A study has provided new insight into the fundamental phenomenon of maternal mitochondrial DNA inheritance. Conducted by Oregon Health & Science University (OHSU) and collaborating institutions, the findings were published in Nature Genetics.
Mitochondrial DNA (mtDNA) is the unique genetic code within the cell's mitochondria and is primarily responsible for energy production. Scientists have long known that mtDNA is transmitted only through the mother's egg and that the father's sperm contributes no mitochondrial genetic information. The precise reason for this mechanism, however, has remained debated.
Earlier theories proposed that sperm mtDNA was removed during fertilization by an immune-like “search and destroy” mechanism. The new study reveals a deeper explanation: although mature sperm carry a small number of mitochondria, those mitochondria do not contain intact mtDNA.
The researchers found that sperm lack both intact mtDNA and mitochondrial transcription factor A (TFAM), an essential protein for maintaining mitochondrial DNA. This means sperm cannot pass mitochondrial genetic information to offspring.
Dr. Shoukhrat Mitalipov, director of OHSU's Center for Embryonic Cell and Gene Therapy, explained, “Sperm do bring about 100 mitochondria at fertilization, but they do not carry any mtDNA.”
The team suggested this may relate to sperm biology. Sperm use substantial mitochondrial energy while swimming toward the egg, which may cause mutations to accumulate in their mtDNA. Eggs, by contrast, rely mainly on surrounding cells for energy during development and use their own mitochondria less, allowing their mtDNA to remain relatively intact.
Dr. Mitalipov noted, “Eggs can transmit higher-quality mitochondrial DNA partly because they do not rely on mitochondria for energy.”
Each sperm carries about 100 mitochondria, while an egg may contain hundreds of thousands. Because egg mtDNA is relatively free of mutations, exclusive maternal transmission is considered an evolutionary advantage that may reduce the risk of mtDNA mutation-related disease in offspring.
Mitochondrial DNA mutations can cause potentially fatal diseases affecting energy-intensive organs such as the heart, muscles, and brain. To help mothers avoid passing known mtDNA diseases to their children, Dr. Mitalipov developed mitochondrial replacement therapy, which uses mtDNA from a healthy donor egg during in vitro fertilization to replace mutated mtDNA.
Although the U.S. Congress currently prevents the Food and Drug Administration (FDA) from reviewing clinical trials that use this technology, trials have been conducted in countries including the United Kingdom and Greece to prevent disease and treat infertility.
The discovery has important implications for human fertility and germ cell therapies. Researchers said that understanding TFAM's role in sperm maturation and fertilization may provide key insights for treating some forms of infertility and improving assisted reproductive technology.
News | Why Is Mitochondrial DNA Inherited Only from the Mother? New Research Identifies a Key Reason
News | Why Is Mitochondrial DNA Inherited Only from the Mother? New Research Identifies a Key Reason
A study has provided new insight into the fundamental phenomenon of maternal mitochondrial DNA inheritance. Conducted by Oregon Health & Science University (OHSU) and collaborating institutions, the findings were published in Nature Genetics.
Mitochondrial DNA (mtDNA) is the unique genetic code within the cell's mitochondria and is primarily responsible for energy production. Scientists have long known that mtDNA is transmitted only through the mother's egg and that the father's sperm contributes no mitochondrial genetic information. The precise reason for this mechanism, however, has remained debated.
Earlier theories proposed that sperm mtDNA was removed during fertilization by an immune-like “search and destroy” mechanism. The new study reveals a deeper explanation: although mature sperm carry a small number of mitochondria, those mitochondria do not contain intact mtDNA.
The researchers found that sperm lack both intact mtDNA and mitochondrial transcription factor A (TFAM), an essential protein for maintaining mitochondrial DNA. This means sperm cannot pass mitochondrial genetic information to offspring.
Dr. Shoukhrat Mitalipov, director of OHSU's Center for Embryonic Cell and Gene Therapy, explained, “Sperm do bring about 100 mitochondria at fertilization, but they do not carry any mtDNA.”
The team suggested this may relate to sperm biology. Sperm use substantial mitochondrial energy while swimming toward the egg, which may cause mutations to accumulate in their mtDNA. Eggs, by contrast, rely mainly on surrounding cells for energy during development and use their own mitochondria less, allowing their mtDNA to remain relatively intact.
Dr. Mitalipov noted, “Eggs can transmit higher-quality mitochondrial DNA partly because they do not rely on mitochondria for energy.”
Each sperm carries about 100 mitochondria, while an egg may contain hundreds of thousands. Because egg mtDNA is relatively free of mutations, exclusive maternal transmission is considered an evolutionary advantage that may reduce the risk of mtDNA mutation-related disease in offspring.
Mitochondrial DNA mutations can cause potentially fatal diseases affecting energy-intensive organs such as the heart, muscles, and brain. To help mothers avoid passing known mtDNA diseases to their children, Dr. Mitalipov developed mitochondrial replacement therapy, which uses mtDNA from a healthy donor egg during in vitro fertilization to replace mutated mtDNA.
Although the U.S. Congress currently prevents the Food and Drug Administration (FDA) from reviewing clinical trials that use this technology, trials have been conducted in countries including the United Kingdom and Greece to prevent disease and treat infertility.
The discovery has important implications for human fertility and germ cell therapies. Researchers said that understanding TFAM's role in sperm maturation and fertilization may provide key insights for treating some forms of infertility and improving assisted reproductive technology.
Source:
Compiled from online sources