Development to term of chimaeras between diploid parthenogenetic and fertilised embryos

Abstract

PARTHENOGENETIC mouse embryos have the potential for extensive cellular proliferation as well as differentiation into various cell types^1–3. But this potential has been realised only when parthenogenetic embryos have been transferred to extrauterine sites¹, and in spontaneously occurring ovarian teratomas and teratocarcinomas of parthenogenetic origin^2,3. The development of mammalian parthenogenetic embryos in utero is restricted, with no conclusive evidence that they can develop to term^4,5. Several hypotheses have been proposed to account for their poor development. For example, deleterious recessive genes may affect the viability of their cells, possibly because of their extensive homozygosity^2,5, or disorganised growth and limited life span may result from anomalies of cellular interactions⁵. But the extensive cellular proliferation and differentiation of parthenogenetically derived cells which occurs in extrauterine sites is not entirely consistent with these explanations, and indicates that parthenogenones probably have a relatively stable genetic constitution. Indeed, these studies stress the likely importance of cellular environment for cytodifferentiation, provided in this instance by the extrauterine host tissue. There is a precedent for supposing that if the environment is critical for cytodifferentiation, parthenogenetic cells should be able to form chimaeras with cells derived from fertilised embryos⁶. Teratocarcinoma cells^7,8 and cells carrying known lethal alleles^9,10 can develop into viable chimaeras when aggregated with cells from normal embryos. Previous attempts to achieve development to term of aggregation chimaeras between parthenogenetic and fertilised embryos were apparently unsuccessful¹¹. We have introduced inner cell masses (ICMs) from diploid ,parthenogenetic embryos into intact fertilised mouse blastocysts, and we report here the development of a chimaera to term.