New research provides insight into the basic scientific principle that mitochondrial DNA -; distinct genetic code embedded in an organelle that serves as the power unit of every cell in the body -; it is transmitted exclusively by the mother.
A collaborative study between Oregon Health & Science University and other institutions, published today in the journal Genetics of nature.
Scientists have long recognized that mitochondrial DNA, or mtDNA, comes exclusively from egg cells in humans, meaning that only the mother contributes the genetic code carried by the thousands of mitochondria necessary for energy production in every cell in the body.
It was previously believed that paternal mtDNA was eliminated soon after the sperm fuses with the oocyte or developing egg during fertilization, probably through a seek-and-destroy immune response.
However, the study found that while mature sperm cells carry a small number of mitochondria, they lack intact mtDNA.
We found that each sperm brings about 100 mitochondria as organelles when it fertilizes an egg, but there is no mtDNA in them.”
Shoukhrat Mitalipov, PhD, Director, Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University
The researchers found that the sperm not only lacked intact mtDNA, but also lacked a protein necessary to maintain mtDNA, known as mitochondrial transcription factor A, or TFAM.
Scientists aren’t sure why sperm aren’t allowed to contribute mtDNA, but Mitalipov theorizes that it may have to do with the fact that sperm use a lot of mitochondrial energy in their biological drive to fertilize an egg. It would thus accumulate mutations in the mtDNA. Developing eggs, known as oocytes, in contrast, draw energy primarily from surrounding cells, not from their own mitochondria, so they keep their mtDNA relatively intact.
“Eggs transmit really good mtDNA at least in part because they don’t use mitochondria as an energy source,” Mitalipov said.
About 100 organelles in the sperm are flooded with hundreds of thousands of mitochondria stored in each egg cell -; each carries 37 genes in mitochondrial DNA. The contribution of only maternal mtDNA is thought to provide an evolutionary advantage by limiting the risk of accumulating disease-causing mtDNA mutations in the offspring.
Mitochondria control respiration and energy production in every cell of the body, so mutations in mtDNA can cause a range of potentially fatal disorders affecting organs with high energy demands, such as the heart, muscles and brain.
To help mothers prevent the transmission of known mtDNA disorders to their children, Mitalipov pioneered a method called mitochondrial replacement therapy to replace mutant mtDNA through in vitro fertilization with healthy mtDNA from donor eggs.
Congress has prevented the Food and Drug Administration from overseeing clinical trials using the procedure in the US, so clinical trials are instead conducted overseas, including clinical trials in the UK to prevent disease and in Greece to treat infertility.
The new discovery has important implications for human fertility and germ cell therapy, the researchers write.
“Understanding the role of TFAM during sperm maturation and its function during fertilization may hold the key to our ability to treat certain infertility disorders and increase the effectiveness of assisted reproductive technologies,” said corresponding author Dmitry. Temiakov, Ph.D.D.molecular biologist at Thomas Jefferson University in Philadelphia.
Source:
Link to journal:
Lee, W., etc al. (2023) Molecular basis for maternal inheritance of human mitochondrial DNA. Nature Genetics. doi.org/10.1038/s41588-023-01505-9.
