Estrogen receptors regulate sex disparity in the immune responses during zebrafish liver regeneration following partial hepatectomy.

Abstract

Immune responses play crucial roles in liver regeneration following partial hepatectomy (PH). Previous studies using the rodent PH models have shown that liver regeneration following PH has sex disparity. However, the sex disparity in the immune responses to PH and its relationship with sex-biased liver regeneration has not been investigated yet. In the current study, we applied the zebrafish PH model to study these issues and found that male zebrafish have earlier immune responses than female zebrafish following PH. By depleting macrophages before PH, we confirmed that liver regeneration following PH in zebrafish requires the participation of macrophages. In addition, activation of estrogen receptors inhibited the upregulation of inflammatory factors in male livers and reduced hepatocyte proliferation at the early stage of PH-induced liver regeneration. Therefore, the male-biased liver regeneration and immune responses in zebrafish following PH could be regulated by estrogen receptor activities.