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Aim It is well known that menopause could worsen agerelated ventricular concentric remodeling and increased incidence of arrhythmias following estrogen (E2) deficiency.However, the underlying mechanisms of such phenomena are not fully understood.Mitochondria, as the cellular power station of hearts, play an important role in maintaining normal cardiac function and structure.Therefore, the present study aims to investigate whether mitochondrial compromise and gap junction impairment induced by miR23a is responsible for E2 deficiency associated structural and electrical remodeling.Results: We found mitochondrial structural damages and respiratory function impairment in myocardium of both postmenopausal and OVX mice and E2 supplement reversed mitochondrial dysfunction in OVX mice, suggesting that E2 deficiency could induce mitochondrial compromise in the heart.Then, peroxisome proliferatoractivated receptorγcoactivator 1α (PGC1 α), a key mitochondrial function and biology regulator, was found significantly reduced in both postmenopausal and OVX mice, which could be rescued by E2 delivery, indicating that E2 could positively regulate PGC1 α expression.Next, we found that microRNA23a (miR23a) could be negatively regulated by E2 in both myocardium and cultured cardiomyocytes.Moreover, miR23a could directly downregulate PGC1α expression in cardiomyocytes via binding to its 3UTR of mRNA which implied that miR23a could be critical for the downregulation of PGC1 α under E2 deficiency.Overexpression of miR23a was also found to damage mitochondria in cultured cardiomyocytes, ascribed to PGC1o downregulation.Moreover, we also found cardiac conduction blockage, cardiac gap junctions impaired and Connexin 43(Cx43) expression reduced in the myocardium of postmenopausal rats.The phenomenon was also observed in ovariectomized (OVX) rats, which was attenuated by E2 supplement.Importantly, forced overexpression of miR23a led to gap junction impairment and Cx43 downregulation in cultured cardiomyocytes, which was rescued by suppressing miR23a by transfection of miR23a specific inhibitory oligonucleotide (AMO23a).GJA1 was identified as the target gene of miR23a by luciferase assay.We also found that E2 supplement could reverse cardiac conduction blockage, Cx43 downregulation and gap junction remodeling in postmenopausal rats.Conclusion Taken together, E2 deficiency may cause mitochondrial compromise and aberrant cardiac conductance through miR23amediated PGC1 α and GJA1 downregulation, which may subsequently lead to the menopauseassociated structural and electrical remodeling.This highlights a new insight into molecular mechanism of postmenopause related cardiac conditions at the microRNA level.