"Experimental Chimeras' Removal of Reproductive Barrier Between Sheep and Goat" (1984), by Sabine Meinecke-Tillmann and Burkhard Meinecke

In 1984 Sabine Meinecke-Tillmann and Burkhard Meinecke published their article “Experimental Chimeras — Removal of Reproductive Barrier Between Sheep and Goat” in Nature. Their study conquered the reproductive barrier between sheep and goats through embryo manipulation. Their article appeared in Nature on the same day that a similar experiment, conducted by Carole Fehilly, Steen Willadsen, and Elizabeth Tucker was published regarding reproductive barriers between sheep and goats. In previous experiments involving the transplantation of sheep embryos into recipient goats or vice versa, the embryos did not survive past the initial weeks of pregnancy. Hybridization experiments had also failed between the species. Although scientists were unsure of the reasons that hybrid eggs from donor sheep did not survive, they attributed the death of the hybrid eggs from donor goats to immunological responses. Meinecke-Tillmann and Meinecke created interspecific chimeric embryos in order to address the reproductive obstacles between the species. These embryos were transferred to sheep, and a sheep successfully brought a goat kid to term.

In their study Meinecke-Tillmann and Meinecke worked with sheep and goat embryos to create interspecific chimeric embryos. After the estrus cycles of both species were coordinated and breeding occurred, they collected embryos. Goat embryos and sheep embryos differed in age by twenty-four hours. Meinecke-Tillmann and Meinecke created interspecific chimeric embryos two different ways: by joining single blastomeres from 4-cell sheep embryos with two blastomeres from 8-cell goat embryos or by joining two blastomeres from early 8-cell sheep embryos with two blastomeres of late 8-cell goat embryos in a pig zona pellucida. In order to protect the cells, the slit in the zona pellucida, or outer membrane, was covered by another zona pellucida that surrounded the entire aggregated embryo. They retrieved the embryos after blastulation was thought to occur and then transplanted the embryos that entered into the blastocyst stage into recipient sheep.

During the experiment Meinecke-Tillman and Meinecke obtained fifteen interspecific chimeric embryos of which nine formed common blastocysts. Four embryos reached the blastocyst stage, one of them failing to fully cleave, and a couple developed into a combination of two small blastocysts in a common zona pellucida. There were fifteen sheep recipients, eight of which became pregnant. Three surrogate mothers gave birth to two sheep lambs—one live and one stillborn—and one goat lamb. One sheep lamb was stillborn as a result of postponed birth. It was created from two sheep and two goat blastomeres, but one goat blastomere was not incorporated in the common blastocyst. The other sheep lamb was created from two blastocysts in a zona pellucida. The goat lamb developed from the combination of one blastomere from a 4-cell sheep embryo and two blastomeres from an 8-cell goat embryo. Meinecke-Tillmann and Meinecke performed several tests including blood tests, cytogenetic analysis, and breeding experiments and concluded that the animals created did not provide any signs suggesting that they were interspecific chimeras.

Meinecke-Tillmann and Meinecke developed a method to overcome reproductive barriers between sheep and goats. This was accomplished by surrounding the foreign embryo by a protective barrier containing only cells from the same species as the recipient. In their paper they emphasized the significance of creating the embryos with such a barrier in order to protect the foreign embryo from the surrogate mother’s immunological response systems. They stated that the sheep elements, which were at an earlier stage, helped protect the goat elements of the embryo. Meinecke-Tillmann and Meinecke suggested that their method could be valuable for saving endangered species.