Outgrowth of embryonal carcinoma cells from injected blastocysts in vitro correlates with abnormal chimera development in vivo.

Early embryonic cells are capable of regulating the proliferation of some embryonal carcinoma (EC) cells in vivo although other EC lines are not affected. Up to 80% of fetuses are chimeric following injection of P10EC cells into blastocysts and half of these are normal. P19, on the other hand, is not controlled by the embryo and all chimeric fetuses are abnormal. P10 and P19 cells were injected into blastocysts and vesicles of pure trophectoderm and examined following culture. EC cells grew from 62/72 P19-injected blastocysts but from only 7/73 P10-injected blastocysts. Both cell lines grew from injected trophectoderm vesicles in culture: P19 grew from 10/17 injected vesicles and P10 grew from 9/13 injected vesicles, suggesting that trophectoderm alone is not responsible for controlling EC growth. When EC-injected vesicles were transferred to foster mothers, normal development did not ensue, indicating the failure of the trophectoderm to normalize EC cells in vivo. Results indicate that EC-embryo combinations that allow EC outgrowth in vitro are also those that result in incomplete control of EC proliferation in chimeras and that the in vitro system can thus be used to investigate factors in the embryonic environment that control EC proliferation and differentiation.