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Polar Body Genome Transfer for Preventing the Transmission of Inherited Mitochondrial Diseases
Wang Tian, Sha Hongying*, Ji Dongmei, Zhang Helen L., Chen Dawei, Cao Yunxia, Zhu Jianhong
State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Abstract: Inherited mitochondria disease inherit through the maternal line and develop severe systemic diseases. Nuclear genome transfer between patients’ and healthy eggs to replace mutant mtDNAs holds promises to prevent the transmission of mitochondria diseases. This technique is named mitochondria donation， including pronuclei transfer (PNT) and spindle-chromosome complex transfer (ST) before publishing our paper. However， PNT and ST couldn’t thoroughly prevent the transmission of mitochondria diseases. We found polar body (PB) was able to be the prior candidate， since PB contains few mitochondria， and PB nucleus is identical to female nucleus in ooplasm. We compared the effects of different types of germline genome transfer， including ST， PT， PB1T and PB2T in mice. Our results showed reconstructed embryos support normal fertilization and produce live offspring. Genetic analysis confirms that the F1 generation from polar body transfer possesses minimal donor mtDNA compared to the F1 generation of the other procedures. Moreover， the mtDNA genotype remains stable in F2 progeny after polar body transfer， suggesting first polar body transfer (PB1T) has great potential to prevent inherited mtDNA diseases.
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