At about the time Jirtle was doing his mice experiments, Michael Meaney, a neuroendocrinologist at McGill University in Montreal, was working with rats, testing the methylation of a gene important to the stress response—a glucocorticoid receptor gene in the brain. It turns out it’s not just what a mother eats but also how she treats her babies that affects their epigenome—the pattern of epigenetic marks that accumulates throughout development. Some rat mothers are particularly attentive to their pups, excessively licking and nursing during the first week after delivery. Studies have shown that the pups of these mothers are less fearful as adults and less fazed by stressful situations.

Meaney found striking differences in methylation patterns between pups with highly attentive mothers and those with neglectful mothers. Less attentive mothering resulted in more methylation near the glucocorticoid receptor gene, turning it off; better mothering kept it on, producing more receptors and better regulation of the rats’ stress response. To confirm his findings, Meaney transferred pups born to neglectful mothers to highly attentive ones immediately after birth; the methylation patterns of these adoptees were almost indistinguishable from those of the attentive mothers’ natural offspring, and the adopted pups grew up to be as fearless as the natural pups.
Although these epigenetic changes happened only during one crucial period—the first week after delivery—their impact persisted into adulthood. Yet when Meaney injected a compound into adult rats that demethylated key genes, neglected animals became less fearful. His work provides the first evidence that the way a mother takes care of offspring might change them forever by altering the epigenome.

These studies demonstrate how a less than ideal environment during a critical developmental period may have long-lasting effects. Now, Michael Skinner, a molecular bioscientist at Washington State University in Pullman, is going further, showing that such exposure may change the lives of the altered animals’ descendants too.

Skinner exposed pregnant rats to the toxin vinclozolin, a hormonelike compound known as an endocrine disrupter, during days eight through 15 of their embryos’ development—when the cells that will become sperm are particularly open to epigenetic changes. He found that almost all males in four subsequent generations descended from the vinclozolin-exposed rats had far fewer and less vigorous sperm than normal and were also more likely to be infertile. Moreover, these effects appeared to relate to patterns of DNA methylation.

“The exposure to vinclozolin apparently reprogrammed the remethylation in the male germ line permanently,” Skinner says. In a later study, he found that vinclozolin exposure during the same period not only caused reproductive defects but also led to a number of adult diseases, including prostate disease, kidney disease and tumor development. It even dampened the rats’ chances of finding a mate.

Skinner was the first to show that epigenetics propagates the effects of the environmental exposure of one generation to multiple subsequent generations. “We have a clearly transgenerational effect for four generations and a very high frequency of disease,” he says.

During his years working with the Överkalix data, Kaati has tried to link environmental developments in the parish with possible epigenetic changes in residents. He has followed the lives of people born in 1890, 1905 and 1920 and consulted crop data compiled during the lives of their parents and grandparents. His goal was to find how much food was available to people during one crucial stage of development: the slow growth period (SGP) before puberty begins (between ages eight and 10 for girls and nine and 12 for boys).