News | Study finds a 30% higher DNA mutation rate in offspring of IVF mice
A Genome Research study found that laboratory mice conceived through in vitro fertilization (IVF) had a slightly higher genetic mutation rate than naturally conceived mice, an increase of about 30%. The team stressed that this biological signal warrants attention but cannot be applied directly to humans. More research is needed on the potential genetic effects of assisted reproductive technology on offspring.
The study was led by geneticist Beth Dumont of The Jackson Laboratory. The team compared genomes from naturally conceived mice with those conceived through assisted reproductive procedures including ovarian stimulation, IVF and embryo transfer. Mice born through these procedures had more new single-nucleotide variants (SNVs), or small changes to one letter of the DNA sequence.
Dumont said the mutations were distributed throughout the genome rather than concentrated in key genes, and arose at a similar time to mutations in naturally conceived mice. Assisted reproduction may therefore increase the overall probability of mutation without changing the developmental stage at which mutations occur. "Even when the mutation rate increases, most mutations are neutral changes scattered across the genome and do not affect the individual's phenotype," she said. "This is not a large increase in absolute terms, and the chance of a harmful mutation is very small, almost negligible."
Scientists generally estimate that fewer than 2% of new mutations are harmful. Even with a 30% increase, the absolute number remains very low: the team estimated roughly one additional potentially harmful DNA change for every 50 IVF-conceived mice. Dumont compared the effect with increasing a male mouse's age by about 30 weeks.
The biological mechanism remains unclear. Possible factors include ovarian-stimulation hormones causing oocytes to re-enter an error-prone stage of meiosis, or physical and chemical effects of laboratory embryo culture. The team said the next step is to separate the individual IVF procedures and identify whether a particular step drives the increase.
The researchers emphasized that the study does not show the same effect in human IVF. Mouse and human reproductive biology differ substantially, as do clinical IVF procedures and laboratory animal models. The reasons patients need IVF may also include environmental or health factors affecting genetic stability.
"Our results do not directly show that human IVF causes mutations, but the literature contains indications that certain steps may be associated with genetic changes," Dumont said. "This deserves further study so patients can be as fully informed as possible."
Laura Blanco-Berdugo and Alexis Garretson of The Jackson Laboratory also contributed. Funding came from laboratory startup funds and the National Institute of General Medical Sciences Maximizing Investigators' Research Award (R35 GM133415).
News | Study finds a 30% higher DNA mutation rate in offspring of IVF mice
News | Study finds a 30% higher DNA mutation rate in offspring of IVF mice
A Genome Research study found that laboratory mice conceived through in vitro fertilization (IVF) had a slightly higher genetic mutation rate than naturally conceived mice, an increase of about 30%. The team stressed that this biological signal warrants attention but cannot be applied directly to humans. More research is needed on the potential genetic effects of assisted reproductive technology on offspring.
The study was led by geneticist Beth Dumont of The Jackson Laboratory. The team compared genomes from naturally conceived mice with those conceived through assisted reproductive procedures including ovarian stimulation, IVF and embryo transfer. Mice born through these procedures had more new single-nucleotide variants (SNVs), or small changes to one letter of the DNA sequence.
Dumont said the mutations were distributed throughout the genome rather than concentrated in key genes, and arose at a similar time to mutations in naturally conceived mice. Assisted reproduction may therefore increase the overall probability of mutation without changing the developmental stage at which mutations occur. "Even when the mutation rate increases, most mutations are neutral changes scattered across the genome and do not affect the individual's phenotype," she said. "This is not a large increase in absolute terms, and the chance of a harmful mutation is very small, almost negligible."
Scientists generally estimate that fewer than 2% of new mutations are harmful. Even with a 30% increase, the absolute number remains very low: the team estimated roughly one additional potentially harmful DNA change for every 50 IVF-conceived mice. Dumont compared the effect with increasing a male mouse's age by about 30 weeks.
The biological mechanism remains unclear. Possible factors include ovarian-stimulation hormones causing oocytes to re-enter an error-prone stage of meiosis, or physical and chemical effects of laboratory embryo culture. The team said the next step is to separate the individual IVF procedures and identify whether a particular step drives the increase.
The researchers emphasized that the study does not show the same effect in human IVF. Mouse and human reproductive biology differ substantially, as do clinical IVF procedures and laboratory animal models. The reasons patients need IVF may also include environmental or health factors affecting genetic stability.
"Our results do not directly show that human IVF causes mutations, but the literature contains indications that certain steps may be associated with genetic changes," Dumont said. "This deserves further study so patients can be as fully informed as possible."
Laura Blanco-Berdugo and Alexis Garretson of The Jackson Laboratory also contributed. Funding came from laboratory startup funds and the National Institute of General Medical Sciences Maximizing Investigators' Research Award (R35 GM133415).
Story source:
Collected online