Abnormal development of the trophoblast after nuclear transfer in the mouse
Résumé
Reprogramming of a nuclear activity through nuclear transfer (NT) into enucleated oocytes is a very inefficient process although it gives rise to living cloned animals. We and others have observed pluripotency is quite faithfully reprogrammed in NT-embryos, as indicated by the efficient derivation of embryonic stem cells from early and late NT-epiblast. Moreover, the differentiation of the epiblast in vivo is globally unaffected in NT embryos. Two critical periods have been identified during the development of clones. The high rate of lethality at the time of implantation can be partially rescued by wild type ES or ICM cells, suggesting a cell-autonomous defect in the NT epiblast. Peri-gastrulation stage is then characterized by appearance of defined morphological defects, among which an abnormal growth of the trophoblast, well correlated with the placentomegaly affecting any clones still alive at foetal stages. Trophoblast stem cells were derived from NT embryos. Remarkably, we observed that while epiblast-produced growth factors Fgf4 and Activin exert a fine-tuned control on the balance between self-renewal and differentiation of control TS cells, as they do in vivo, ntTS cells exhibit a reduced dependency upon their micro-environment. Analysis of placental growth in chimeras made by combining tetraploid and diploid embryos suggest that placentomegaly may in fact arise from an abnormal cross-talk of the epiblast with the trophoblast.