Prenatal lipopolysaccharide disrupts maternal behavior, reduces nest odor preference in pups, and induces anxiety: studies of F1 and F2 generations.

The present study analyzed the transgenerational effects of lipopolysaccharide (LPS; 100 μg/kg) administration on gestational day 18 (GD18) of parental generation on maternal-pups interaction of F1 and F2 generations. Also the long term behavioral effects were observed in male of F2 generation. In F1 generation, the reproductive performance, maternal behavior, maternal aggressive behavior, and general activity in the open field in adulthood were analyzed. In F2 generation, body weight at birth and at weaning, nest odor preference, and general activity in the open field and elevated plus maze in adulthood were assessed. Compared to controls, results showed that in the F1 generation, prenatal LPS exposure (1) increased the latency to full maternal behavior, but all of the females grouped the pups and presented full maternal behavior, (2) reduced the total time boxing and fighting, increased the frequency of retrieving the pups, and increased the number of bites, and (3) did not affect reproductive performance or general activity. In F2 generation, compared with controls, the LPS group exhibited (1) a decrease in body weight at weaning, (2) a decrease in nest odor preference, (3) a decrease in the percentage of time spent in the open arms, a decrease in the percentage of time spent in the center, and an increase in the time spent in the closed arms in the elevated plus maze, and (Huang et al.) no affect behavior in the open field. Prenatal LPS exposure improved maternal care in the F1 generation with regard to nursing and pup survival but did not improve the motivational parameters of maternal behavior likely because of a reduction of maternal stimulation by the pups. In the F2 generation, the reduction of nest odor preference in the pups suggests a less maternal recognition. In adulthood, these rats exhibited increased anxiety-like behavior. These data did not result from motor alterations because rats in both the F1 and F2 generations did not show alterations in open field behavior. This transfer of information across generations likely occurred through nongenetic means because the endotoxin was administered at the end of pregnancy. These results may have implications for clinical therapeutics in human disorders and evolution.