Contrasting bisphenol A exposure concentrations elicit distinct testicular energy-metabolic responses associated with male reproductive impairment in rare minnow.
Abstract
Bisphenol A (BPA) is a widespread endocrine-disrupting chemical that impairs male fish reproduction, yet how testicular energy metabolism responds to contrasting BPA exposures and its associations with redox and mitochondrial dysfunction remain poorly understood. Male rare minnows (Gobiocypris rarus) were exposed to 0, 15, or 225 μg/L BPA for 21 and 42 days. Reproductive performance, plasma androgens, testicular redox status, germ-cell apoptosis, and mitochondrial function were assessed, together with targeted energy metabolomics, untargeted metabolomics, and transcriptomics at 42 days. BPA reduced fertilization capacity in both exposed groups after 21 days, whereas impaired sperm movement duration became evident at 42 days, particularly at 225 μg/L, without significant changes in somatic growth, gonadal indices, or sperm density. At 42 days, 15 μg/L BPA induced selective metabolic remodeling involving glycolytic intermediates, substrate allocation, and nucleotide metabolism, accompanied by reduced sperm mitochondrial membrane potential but limited oxidative injury and germ-cell apoptosis. In contrast, 225 μg/L BPA was associated with broader metabolic disturbances, pronounced redox imbalance, reduced mitochondrial complex I activity, mitochondrial ultrastructural abnormalities, and increased germ-cell apoptosis. Notably, testicular ATP levels remained unchanged in both BPA groups despite alterations in energy-related metabolites. Integrated multi-omics analyses further revealed distinct molecular response patterns, with broader alterations in carbon, nucleotide, activated-sugar, and endocrine-related pathways at the higher concentration. These findings identify distinct testicular energy-metabolic response patterns under contrasting BPA exposures and highlight their associations with mitochondrial dysfunction and male reproductive impairment.
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