Estrogen Accelerates Heart Regeneration by Promoting the Inflammatory Response in Zebrafish

Overview

Journal J Endocrinol

Specialty Endocrinology

Date 2020 Jan 25

PMID 31977314

Citations 22

Authors

Shisan Xu

Fangjing Xie

Li Tian

Samane Fallah

Fatemeh Babaei

Sinai H C Manno

Francis A M Manno

Lina Zhu

Kin Fung Wong

Yimin Liang

Rajkumar Ramalingam

Lei Sun

Xin Wang

Robert Plumb

Lee Gethings

Yun Wah Lam

Shuk Han Cheng

Affiliations

Soon will be listed here.

Abstract

Sexual differences have been observed in the onset and prognosis of human cardiovascular diseases, but the underlying mechanisms are not clear. Here, we found that zebrafish heart regeneration is faster in females, can be accelerated by estrogen and is suppressed by the estrogen-antagonist tamoxifen. Injuries to the zebrafish heart, but not other tissues, increased plasma estrogen levels and the expression of estrogen receptors, especially esr2a. The resulting endocrine disruption induces the expression of the female-specific protein vitellogenin in male zebrafish. Transcriptomic analyses suggested heart injuries triggered pronounced immune and inflammatory responses in females. These responses, previously shown to elicit heart regeneration, could be enhanced by estrogen treatment in males and reduced by tamoxifen in females. Furthermore, a prior exposure to estrogen preconditioned the zebrafish heart for an accelerated regeneration. Altogether, this study reveals that heart regeneration is modulated by an estrogen-inducible inflammatory response to cardiac injury. These findings elucidate a previously unknown layer of control in zebrafish heart regeneration and provide a new model system for the study of sexual differences in human cardiac repair.

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