Multi-generational carcinogenesis from diethylstilbestrol investigated by blastocyst transfers in mice

Previous studies have shown that a carcinogenic effect can be transmitted from female mice exposed prenatally to diethylstilbestrol (DES) to their female offspring. Furthermore, male mice exposed pre-natally to DES can transmit a carcinogenic effect to their offspring through their germ cells. To study how multi-generational carcinogenesis is transmitted through females exposed pre-natally to DES, the technique of blastocyst transfer was utilized. Blastocysts from strain CD-1 mice exposed pre-natally to vehicle were transferred to mice exposed pre-natally to DES. Among 143 offspring from these transfers, there were 10 ovarian adenomas and 10 uterine adenocarcinomas. Among 92 offspring from blastocyst transfers between mice exposed pre-natally to vehicle only, there was 1 ovarian adenoma and 1 uterine adenocarcinoma. Thus the pre-natal exposure of the host to DES produced a maternal environment which increased the incidence of ovarian and uterine tumors. The reverse type of transfer was also performed, in which blastocysts from female mice exposed pre-natally to DES were transferred into mice exposed to vehicle only pre-natally. Among 99 offspring derived from DES-exposed germ cells, 6 developed ovarian adenomas and 16 developed uterine adenocarcinomas. Thus DES also has a multi-generational effect transmitted through the blastocyst, which is consistent with fetal germ cell mutation from DES.