Genetic and Epigenetic Evidence for Nonestrogenic Disruption of Otolith Development by Bisphenol A in Zebrafish

Abstract

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical (EDC) that has estrogenic activities. In addition to disrupting reproductive development and function via estrogenic signaling pathways, BPA can also interfere with nonreproductive functions through nonestrogenic pathways; however, the mechanisms underlying such nonestrogenic activities are not well understood. In this study, we demonstrated that BPA could disrupt otolith formation during the early development of zebrafish with long-lasting ethological effects. Using multiple mutants of estrogen receptors, we provided strong genetic evidence that the BPA-induced otolith malformation was independent of estrogen signaling. Transcriptome analysis revealed that two genes related to otolith development, otopetrin 1 (otop1) and starmaker (stm), decreased their expression significantly after BPA exposure. Knockout of both otop1 and stm genes could phenocopy the BPA-induced otolith malformation, while microinjection of their mRNAs could rescue the BPA-induced abnormalities of otolith formation. Further experiments showed that BPA inhibited the expression of otop1 and stm by activating the MEK/ERK-EZH2-H3K27me3 signaling pathway. Taken together, our study provided comprehensive genetic and molecular evidence that BPA induced the otolith malformation through nonestrogenic pathway during zebrafish early development and its activities involved epigenetic control of key genes (e.g., otop1 and stm) participating in otolith formation.

In Search of a Target Gene for a Desirable Phenotype in Aquaculture: Genome Editing of Cyprinidae and Salmonidae Species

“…Genome editing has been used to model human tumors such as liver cancer [70], paraganglioma [71], skin melanoma [72], and epithelioid sarcoma [73]. Among neurologic diseases, amyotrophic lateral sclerosis [74], epilepsy [75][76][77][78][79] [105,106], inner ear [107][108][109][110][111], vestibular apparatus [111], otoliths [112], brain [89, [113][114][115][116][117], neural tissue [118][119][120][121][122][123][124][125][126][127] and nervous system [128][129][130], heart [131][132][133][134][135][136][137][138][139], cardiomyocytes [140][141]…”

“…Much of the work has focused on the role of specific genes in organ formation and function, including the lens [ 99 ], retina [ 100 , 101 , 102 ], optic neurons [ 103 , 104 ], ocular vessels [ 105 , 106 ], inner ear [ 107 , 108 , 109 , 110 , 111 ], vestibular apparatus [ 111 ], otoliths [ 112 ], brain [ 89 , 113 , 114 , 115 , 116 , 117 ], neural tissue [ 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 ] and nervous system [ 128 , 129 , 130 ], heart [ 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 ], cardiomyocytes [ 140 , 141 , 142 , 143 ], including cardiovascular rate control [ 144 , 145 ], blood vessels [ 146 , 147 ,…”

3D-MPEA: A Graph Attention Model-Guided Computational Approach for Annotating Unknown Metabolites in Interactomics via Mass Spectrometry-Focused Multilayer Molecular Networking

“…During the past decade, the potential environmental pollution and risk of ingestion mediated by the ubiquitous application of 2,2-bis­(4-hydroxyphenyl)­propane (BPA, CAS 80–05–7, C 15 H 16 O 2 ) have attracted considerable attention. , The migration through packaging and accumulation along the food chain was a vital track for human exposure to 2,2-bis­(4-hydroxyphenyl)­propane. Despite the maximum residue limits (MRLs) being relied upon to restrain the enrichment of 2,2-bis­(4-hydroxyphenyl)­propane in the environment along the food chain, − the potential consumption risks mediated by 2,2-bis­(4-hydroxyphenyl)­propane within MRLs are still indefinite.…”