Enhanced genetic integrity in mouse germ cells.

Genetically based diseases constitute a major human health burden, and de novo germline mutations represent a source of heritable genetic alterations that can cause such disorders in offspring. The availability of transgenic rodent systems with recoverable, mutation reporter genes has been used to assess the occurrence of spontaneous point mutations in germline cells. Previous studies using the lacI mutation reporter transgenic mouse system showed that the frequency of spontaneous mutations is significantly lower in advanced male germ cells than in somatic cell types from the same individuals.

Epigenetic regulation of genetic integrity is reprogrammed during cloning.

Cloning by somatic cell nuclear transfer (SCNT) circumvents processes that normally function during gametogenesis to prepare the gamete genomes to support development of new progeny following fertilization. One such process is enhanced maintenance of genetic integrity in germ cells, such that germ cells typically carry fewer spontaneously acquired mutations than somatic cells in the same individual. Thus, embryos produced from somatic cells by SCNT could directly inherit more mutations than naturally conceived embryos.

Assisted reproductive technologies do not alter mutation frequency or spectrum.

Assisted reproductive technologies (ARTs) have now contributed to the birth of >3 million babies worldwide, but concerns remain regarding the safety of these methods. We have used a transgenic mouse model to examine the effects of ARTs on the frequency and spectrum of point mutations in midgestation mouse fetuses produced by either natural reproduction or various methods of ART, including preimplantation culture, embryo transfer, in vitro fertilization, intracytoplasmic sperm injection, and round spermatid injection. Our results show that there is no significant difference in the frequency or spectrum of de novo point mutations found in naturally conceived fetuses and fetuses produced by in vitro fertilization, intracytoplasmic sperm injection, or round spermatid injection.