Paternal systemic inflammation induces offspring programming of growth and liver regeneration in association with Igf2 upregulation.

Recent studies suggest that stress can lead to variations in offspring development. However, whether paternal systemic inflammation induces phenotypic changes in the offspring remains unclear. Here, we established an in vivo mouse model of systemic inflammation and investigated the long-term consequences on the offspring. Male, but not female offspring derived from inflammatory fathers (LPS-F1) grew faster than those derived from the control fathers (CON-F1). Moreover, the LPS-F1 males had higher capacity for liver regeneration after injury, as indicated by decreased hepatic fibrosis, apoptosis, and increased hepatocyte proliferation upon carbon tetrachloride challenge. Insulin-like growth factor 2 (Igf2), a key mitogen that drives growth and liver regeneration, was significantly upregulated in the livers of male, but not female offspring from fathers with inflammation. Taken together, paternal inflammation alters the hepatic Igf2 expression and reprograms growth and liver regeneration in male but not female offspring.