Maternal preconceptional inflammation transgenerationally alters metabolic and behavioral phenotypes in offspring.

Aims: Evidence is accumulating that maternal inflammation induces phenotypic changes in the next generation. However, whether maternal preconceptional inflammation alters metabolic and behavioral phenotypes in offspring remains poorly understood.

Main Methods: Female mice were injected with either lipopolysaccharide or saline to establish the inflammatory model and then allowed to mate with normal males. Offspring from both control and inflammatory dams were subsequently given chow diet and water ad libitum, without any challenge, for metabolic and behavioral tests.

Key Findings: Male offspring derived from inflammatory mothers (Inf-F1) maintained on the chow diet developed impaired glucose tolerance and hepatic ectopic fat deposition. Hepatic transcriptome sequencing showed the largest gene changes related to the metabolic pathway. Moreover, Inf-F1 mice exhibited anxiety- and depressive-like behaviors and were accompanied by higher serum corticosterone concentration and lower glucocorticoid receptor abundance in the hippocampus.

Significance: The results expand the current knowledge of developmental programming of health and disease to include maternal preconceptional health and provide a basis for understanding metabolic and behavioral alterations in offspring linked to maternal inflammation.