Maintenance of genetic integrity during natural and assisted reproduction

The essence of reproduction involves propagation of genetic information from parents to offspring. In mammals, the frequency of spontaneously acquired mutations is lower in germ-line cells than in somatic cells, reflecting the role played by germ-line cells in the propagation of genetic information and the importance of maintaining genetic integrity in these cells. The Big Blue® transgenic mouse model was used to investigate the frequency and spectrum of: (i) spontaneous point mutations in germ cells as they develop naturally during the life cycle of the mouse; and (ii) acquired mutations that are normally transmitted from parents to offspring during natural and assisted reproduction. The study found that germ cells normally maintain a frequency of spontaneous point mutations that is 5–10-fold lower than that observed in somatic cells from the same individual, leading to embryos with very low frequencies of point mutations in the next generation. No significant differences in the frequency or spectrum of mutations between naturally conceived fetuses and assisted-conception fetuses were observed, indicating that, with respect to maintenance of genetic integrity, these methods are safe. Preliminary analysis of fetuses produced by somatic cell nuclear transfer indicates that maintenance of genetic integrity is regulated in a tissue-specific manner by epigenetic mechanisms that are subject to reprogramming during cloning.