Uterine Environment Boosts Learning Ability in Mouse Offspring

"The Uterine Environment Enhances Cognitive Competence" appears in the current issue of the British scientific journal NeuroReport, published Friday, Feb. 27. Authors are Victor H. Denenberg and Blair J. Hoplight, both of the University of Connecticut at Storrs, and Larry E. Mobraaten of The Jackson Laboratory.

"It's well-known that malnutrition, drugs, alcohol, and other factors can have devastating effects on fetuses," says Dr. Denenberg, who has worked as a visiting investigator at The Jackson Laboratory. "But this is one of the first studies to show that a positive uterine environment can have profound effects upon adult cognitive behavior." The research was supported in part by the National Institutes of Health.

The uterine environment study involved genetically identical mouse embryos of a strain known as BXSB/MpMob-+Yaa. The BXSB strain, developed at The Jackson Laboratory, is a popular model for the study of lupus-like autoimmune diseases and such conditions in mice as neocortical ectopias similar to those found in the brains of human dyslexics.

The embryos were divided into three groups for the experiment. The Non-Transfer group consisted of BXSB mothers with natural embryo implantation. The In-Strain Transfer group had BXSB mothers with transplanted embryos. And the Out-Strain Transfer group consisted of non-automimmune CB6F1 hybrid mothers with transplanted embryos. The Non-Transfer and Out-Strain pups were delivered vaginally and reared by their mothers; the In-Strain pups were delivered by Cesarean section and reared by foster CB6F1 hybrid mothers.

At six weeks of age, the offspring from the three groups were given a series of behavioral tests in Dr. Denenberg's laboratory. The tests included paw preference, open-field activity, swimming rotation, water escape learning, discrimination learning, Lashley maze learning, Morris maze learning, and avoidance learning.

The results showed minor differences in overall cognitive ability between the Non-Transfer and In-Strain Transfer groups. But the Out-Strain group of hybrid-uteri mice demonstrated significant cognitive advantages over the other groups and better adaptation to all experimental challenges. Quantitative comparisons in standard deviation units are provided in the NeuroReport article.

Why was the hybrid uterus "better" than others? The researchers note in their paper the unknown influences of non-autoimmunity and hybrid vigor in the CB6F1 mothers. But those influences are considered unlikely to account for such a large difference in cognitive behavior. "We've raised a question," says Dr. Mobraaten. "The answer lies in further experiments to illuminate the genetics of the uterine environment."

***************** The Jackson Laboratory, founded in 1929, is a world leader in mammalian genetics research. With more than 830 employees, the nonprofit, independent facility has a three-fold mission: to conduct basic genetic and biomedical research, train present and future scientists, and provide genetic resources to researchers worldwide.