Transgenerational epigenetic imprints on mate preference

Abstract

Environmental contamination by endocrine-disrupting chemicals (EDC) can have epigenetic effects (by DNA methylation) on the germ line and promote disease across subsequent generations. In natural populations, both sexes may encounter affected as well as unaffected individuals during the breeding season, and any diminution in attractiveness could compromise reproductive success. Here we examine mate preference in male and female rats whose progenitors had been treated with the antiandrogenic fungicide vinclozolin. This effect is sex-specific, and we demonstrate that females three generations removed from the exposure discriminate and prefer males who do not have a history of exposure, whereas similarly epigenetically imprinted males do not exhibit such a preference. The observations suggest that the consequences of EDCs are not just transgenerational but can be "transpopulational", because in many mammalian species, males are the dispersing sex. This result indicates that epigenetic transgenerational inheritance of EDC action represents an unappreciated force in sexual selection. Our observations provide direct experimental evidence for a role of epigenetics as a determinant factor in evolution.

Fig. 1.

Testing apparatus for mate-preference tests. The schematic (Middle) illustrates the regions of interest. Experimental animals were considered to have exhibited a preference if all four feet had crossed the dotted line into the right or left third of the chamber. While in these areas, the time spent at the glass sides or engaged in the following behaviors (Still, Standing/Sniffing, Walking, and Grooming) was quantified. Time spent in the left or right third of the chamber was also calculated for three additional behaviors (Plexiglas, Facial Investigation, and Wire Mesh). Finally, time in the center third was calculated. Also illustrated is the testing chamber with Plexiglas release box in place under fluorescent illumination (Top) or under dim red light with animals in place (Bottom).

Fig. 2.

Epigenetically altered third-generation female rats (EDC lineage, shown in gray bar) whose progenitors were exposed to vinclozolin, a common-use fungicide with endocrine-disrupting (EDC) properties, prefer males from the unexposed control lineage (A Left). Females from an unexposed lineage (control lineage, shown in open bar) show a similar preference for control-lineage males. A score of 0 on the x axis indicates no preference. Data in the positive direction indicate time spent in the third of the chamber by control-lineage males. Data in the negative direction indicate a preference for the EDC-lineage male. A significant preference of all females, regardless of their lineage, was found for the behaviors Still, Walking, Grooming, Plexiglas, and Wire Mesh, as well as in Total preference behaviors (see text). Males, whether from EDC lineage (gray bar) or control lineage (open bar), do not show any significant preferences (B Right). A score of 0 on the x axis indicates no preference, and there was no significant positive (toward control lineage) or negative (toward EDC lineage) preference by males, regardless of their lineage, for either lineage of females. Presented are the mean (± 1 SEM) differences in the time spent in each behavior. The various behavioral measures and test are described in Methods.

Fig. 3.

Performance of animals in odor-salience test. Female and male rats have the ability to discriminate odors regardless of their lineage. (A) Both sexes show similar patterns, exploring odors of the opposite sex more than odors of unfamiliar individuals of the same sex or their own familiar odor. Data are expressed as mean percentages of total exploration time (± 1 SEM). (B) EDC-lineage males spend significantly more time exploring control- than EDC-lineage female odors. EDC-lineage females spend significantly more time exploring the odor of a novel EDC- than of a novel control-lineage male.