Histological study of the hypertrophic placentas and open eyelids observed in cloned fetuses

Mice cloned from somatic or ES cells showed signs of phenotypically various abnormalities. These abnormalities are now considered to result from aberrant gene expressions by epigenetic reprogramming errors but it is still unclear when these abnormalities occur and what histological changes occur during the gestation period. To address these issues, we histologically examined the hypertrophic placentas and open eyelids at 12.5, 17.5 and 19.5 days of the gestation period in ES-derived cloned mice that we have previously reported. In the placentas, the histology revealed that the hypertrophy had already occurred at 12.5 dpc and that the main change was the proliferation of trophoblast cells in the labyrinth layer. In the fetuses and placentas at 17.5 and 19.5 dpc, extensive proliferation of spongiotrophoblast and glycogen cells in the spongiotrophoblast layer and enlarged trophoblast giant cells were observed. Open eyelids in cloned mice were observed from 17.5 dpc, whereas the eyelids of the control mice had already been closed. The histology showed the malformation of eyelids where the formation of the stratum corneum and stratum granulosum in the epidermis was insufficient. Based on the histology described here, further comparative studies of the gene expression and histology of abnormalities seen in cloned mice and in gene-targeted and spontaneously mutated mice with similar phenotypic abnormalities could help illuminate these abnormalities and could contribute to the development of somatic cloning technology.