Vitamin D3 regulates sperm mitochondrial function essential for zebrafish reproductive ability: insights into non-classical roles

Vitamin D (VD) has attracted increasing research interest in recent years, mainly after several "non-classical" targets were identified, including the reproductive organs. Cytochrome P450 family member 27b1 (Cyp27b1) is the key enzyme for the conversion of VD3 to the active form 1,25(OH)2D3, which catalyzes the hydroxylation of 25(OH)D3 at the 1α position. Cyp27b1 is expressed in oocytes and testicular Sertoli cells, suggesting that VD plays an important role in the regulation of reproductive physiology. This study was aimed to investigate the influence of VD3 on male zebrafish reproduction by administering different levels of VD3 (0, 1400, and 11 200 IU/kg) and creating cyp27b1 knockout zebrafish models. The findings revealed that the dietary level of VD3 and the knockout of the cyp27b1 gene did not affect zebrafish germ cell development or spermatogenesis. However, VD3 deficiency impaired E2 and T synthesis, reduced sperm motility, resulted in mitochondrial dysfunction, blocked mitochondrial biogenesis, and reduced adenosine triphosphate (ATP) content. Additionally, the study found that VD3 deficiency in male zebrafish did not impact the normal growth and development of offspring embryos. In summary, this research demonstrated the role of VD3 in regulating sperm motility by modulating mitochondrial function and biogenesis to regulate ATP synthesis. This study reveals a novel role of VD3 in reproductive processes and provides a new insight for understanding the role of VD3 in animal and human reproductive health.