Prenatal lipopolysaccharide exposure affects sexual dimorphism in different germlines of mice with a depressive phenotype

• Female and male mice were selected for depressive (D) and non-depressive-like (ND) behaviors.
• F0 pregnant females received lipopolysaccharide or saline solution, thus exposing F1 offspring prenatally.
• Lipopolysaccharide increased the proportion of male D and ND mice in the F1 and F2 generations.
• Lipopolysaccharide altered sexual dimorphism in female D mice of the F2 generation.
• The transmission of sexual dimorphism of the phenotypes was observed across generations.

The objective of the present study was to investigate whether prenatal lipopolysaccharide (LPS) administration modifies the expression of depressive and non-depressive-like behavior in male and female mice across two generations. The sexual dimorphism of these mice was also examined in the open-field test. Male and female mice of the parental (F0) generation were selected for depressive- or non-depressive-like behavioral profiles using the tail suspension test (TST). Animals with similar profiles were matched for further mating. On gestation day (GD) 15, pregnant F0 mice received LPS (100 μg/kg, i.p.) and were allowed to nurture their offspring freely. Adult male and female of the F1 generation were then selected according to behavioral profiles and observed in the open field. Male and female mice of the two behavioral profiles were then mated to obtain the F2 generation. Adults from the F2 generation were also behaviorally phenotyped, and open field behavior was assessed. Male mice that were selected for depressive- and non-depressive-like behaviors and treated or not with LPS in the parental generation exhibited similar proportions of behavioral profiles in both filial lines, but LPS exposure increased the number of depressive-like behavior. An effect of gender was observed in the F1 and F2 generations, in which male mice were more sensitive to the intergenerational effects of LPS in the TST. These data indicate that prenatal LPS exposure on GD15 in the F0 generation influenced the transmission of depressive- and non-depressive-like behavior across filial lines, with sexual dimorphism between phenotypes.