RT Journal Article SR Electronic T1 Estrogen accelerates heart regeneration by promoting inflammatory responses in zebrafish JF bioRxiv FD Cold Spring Harbor Laboratory SP 616250 DO 10.1101/616250 A1 Shisan Xu A1 Fangjing Xie A1 Samane Fallah A1 Fatemeh Babaei A1 Lina Zhu A1 Kin Fung Wong A1 Yimin Liang A1 Rajkumar Ramalingam A1 Lei Sun A1 Xin Wang A1 Yun Wah Lam A1 Shuk Han Cheng YR 2019 UL http://biorxiv.org/content/early/2019/07/18/616250.abstract AB Sexual differences are observed in the onset and prognosis of human cardiovascular diseases, but the underlying mechanisms are not clear. Here, we report that zebrafish heart regeneration is faster in females, can be accelerated by estrogen and suppressed by estrogen-antagonist tamoxifen. Injuries to the heart, but not other tissues, increased plasma estrogen level and expression of estrogen receptors, especially esr2a, in zebrafish hearts. The resulting endocrine disruption induces the expression of female-specific protein vitellogenin in male zebrafish. Transcriptomic analyses suggested heart injuries triggered more pronounced immune and inflammatory responses in females. These responses, previously shown to enhance heart regeneration, could be enhanced by estrogen treatment in males and reduced by tamoxifen in female. Furthermore, a brief exposure to estrogen could precondition zebrafish for an accelerated heart regeneration. Altogether, this study reveals that heart regeneration is modulated by an estrogen-inducible inflammatory response to heart injury. These findings elucidate a previously unknown layer of control in zebrafish heart regeneration and provides a new model system for the study of sexual differences in human cardiac repair.