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Fdx1b is an essential electron-providing cofactor to mitochondrial steroidogenic enzymes, which are crucial for glucocorticoid and androgen production in vertebrates. Fdx1b\u2212\/\u2212 zebrafish mutants develop into viable adults in which concentrations of androgens and cortisol are significantly reduced. Adult fdx1b\u2212\/\u2212 mutant zebrafish display predominantly female secondary sex characteristics but may possess either ovaries or testes, confirming that androgen signaling is dispensable for testicular differentiation in this species, as previously demonstrated in androgen receptor mutant zebrafish. Adult male fdx1b\u2212\/\u2212 mutant zebrafish exhibit reduced characteristic breeding behaviors and impaired sperm production, resulting in infertility in standard breeding scenarios. However, eggs collected from wild-type females can be fertilized by the sperm of fdx1b\u2212\/\u2212 mutant males by in vitro fertilization. The testes of fdx1b\u2212\/\u2212 mutant males are disorganized and lack defined seminiferous tubule structure. Expression of several promale and spermatogenic genes is decreased in the testes of fdx1b\u2212\/\u2212 mutant males, including promale transcription factor sox9a and spermatogenic genes igf3 and insl3. This study establishes an androgen- and cortisol-deficient fdx1b zebrafish mutant as a model for understanding the effects of steroid deficiency on sex development and reproductive function. This model will be particularly useful for further investigation of the roles of steroids in spermatogenesis, gonadal development, and regulation of reproductive behavior, thus enabling further elucidation of the physiological consequences of endocrine disruption in vertebrates.<\/jats:p>","DOI":"10.1210\/en.2019-00068","type":"journal-article","created":{"date-parts":[[2019,8,7]],"date-time":"2019-08-07T16:35:36Z","timestamp":1565195736000},"page":"2401-2416","source":"Crossref","is-referenced-by-count":21,"title":["Ferredoxin 1b Deficiency Leads to Testis Disorganization, Impaired Spermatogenesis, and Feminization in Zebrafish"],"prefix":"10.1210","volume":"160","author":[{"given":"James A","family":"Oakes","sequence":"first","affiliation":[{"name":"Department of Oncology & Metabolism, School of Medicine, University of Sheffield, Sheffield, United Kingdom"},{"name":"The Bateson Centre, Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, United 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