Acute Dietary Zinc Deficiency Impairs Sperm Motility but Not Gonadal mRNA Methylation in Mice

Zinc deficiency is associated with impaired male fertility and with reduced DNA and histone methylation in oocytes, but the temporal relationship between acute dietary zinc deficiency and sperm function is unclear. To fill in these gaps, the effects of acute dietary zinc deficiency on sperm function were tested. Five-week-old F1 (DBA × C57BL/6) male and female mice were fed a control diet (29 mg Zn/kg) or zinc-deficient diet (< 1 mg Zn/kg) for 6 days (n = 11/group), a duration selected to model acute zinc depletion based on previous studies demonstrating rapid reproductive defects within a similar timeframe (Tian and Diaz 2012). Sperm number and motility were evaluated by computer-assisted sperm analysis in all animals (n = 11), and testicular histology and DDX4 and YBX2 (MSY2) immunostaining and global m6A levels in testes and liver were measured in a subset of males (n = 6) and in ovaries and liver in females (n = 6) by an ELISA-based assay. Zinc deficiency did not alter body weight but significantly reduced total sperm number recovered from the cauda epididymis and impaired total and progressive motility, straight-line velocity, and hyperactivation. Testes from zinc-deficient males showed reduced thickness of germinal epithelium and increased basement membrane thickness, disorganized seminiferous tubules, and fewer DDX4-positive germ cells, while YBX2-positive cells were largely preserved. Despite these structural and functional defects, zinc deficiency did not significantly change global m6A levels in testes or ovaries, although hepatic m6A methylation was increased in females. These findings demonstrate that a short-term zinc-deficient diet rapidly compromises sperm production, motility, and testicular morphology without measurably altering global gonadal mRNA methylation.