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No evidence for paternal mtDNA transmission to offspring or extra-embryonic tissues after ICSI
D R Marchington1, M S G Scott Brown, V K Lamb
1University Department of Paediatics, Level 4, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
Abstract:
There is a risk that ICSI may increase the transmission of mtDNA diseases to children born after this technique. Knowledge of the fate and transmission of paternal mitochondrial DNA is important since mutations in mitochondrial DNA have been described in oligozoospermic males. We have used an adaptation of solid phase mini-sequencing to exclude the presence of levels of paternal mtDNA >0.001% in ICSI families. This method is more sensitive than those used in previous studies and is sufficient to detect the likely paternal contribution (approximately 0.1-0.5% from simple calculations of expected dilution during fertilization). Using this method, we were able to detect concentrations as low as 0.001% paternal mtDNA in a maternal mtDNA background. No paternal mtDNA was detected in the embryonic (blood or buccal swabs) tissue of children born after ICSI nor in extra-embryonic tissue (placenta or umbilical cord). In conclusion, we did not detect paternal mtDNA in blood, buccal swabs, placenta or umbilical cord of children born after ICSI. We have found no evidence that ICSI increases the risk of paternal transmission of mtDNA and hence of mtDNA disorders.
Insights
Intracytoplasmic sperm injection (ICSI) does not appear to increase the risk of transmitting mitochondrial DNA (mtDNA) diseases. Studies found no paternal mtDNA in children conceived via ICSI, suggesting safety.
Area of Science:
- Genetics
- Reproductive Medicine
- Mitochondrial Biology
Background:
- Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology.
- Mitochondrial DNA (mtDNA) mutations are linked to male infertility (oligozoospermia).
- Potential for paternal mtDNA transmission exists with ICSI, posing a risk for mtDNA diseases.
Purpose of the Study:
- To investigate the risk of paternal mitochondrial DNA (mtDNA) transmission following ICSI.
- To determine if ICSI increases the likelihood of children inheriting paternal mtDNA and associated disorders.
Main Methods:
- Utilized an adapted solid-phase mini-sequencing technique for high-sensitivity detection.
- Quantified paternal mtDNA levels, aiming to detect contributions greater than 0.001%.
- Analyzed embryonic (blood, buccal swabs) and extra-embryonic (placenta, umbilical cord) tissues.
Main Results:
- The sensitive method detected paternal mtDNA at concentrations as low as 0.001%.
- No paternal mtDNA was detected in any embryonic tissues (blood or buccal swabs) from children born after ICSI.
- Absence of paternal mtDNA was also confirmed in extra-embryonic tissues (placenta, umbilical cord).
Conclusions:
- The study found no evidence of paternal mtDNA transmission in children conceived via ICSI.
- ICSI does not appear to elevate the risk of transmitting paternal mtDNA or related mitochondrial disorders.
- Results support the safety of ICSI regarding paternal mitochondrial DNA inheritance.