PFOA exposure decreases acrosome reaction and increases DNA oxidative damage by impairing the sperm head shaping in mice

Perfluorooctanoic acid (PFOA) is a reproductive toxicant, but its effects on sperm head shaping and acrosome reaction remain unknown. Adult male Bal b/c mice were given 0, 2 or 10 mg/kg/day of PFOA for 6 weeks by gavage. Elevated sperm head malformations and decreased acrosome reaction were observed in PFOA-exposed mice. Transmission electron microscopy (TEM) revealed that PFOA exposure caused ultrastructural changes of endoplasmic reticulum, acrosomal granules, acrosomal membrane and nuclear membrane at different phases of acrosome biogenesis. Additionally, key proteins participated in acrosome biogenesis were downregulated in PFOA-exposed mice testes. Alpha-tubulin immunofluorescence indicated that PFOA impaired the manchette structure in elongating spermatids. Western blotting confirmed that key proteins involved in manchette formation were decreased in PFOA-exposed mice testes. Furthermore, PFOA dose-dependently reduced the proteins participating in perinuclear theca (PT) formation. Intriguingly, PFOA inhibited sperm chromatin condensation. Phosphorylation levels of H2A.X, ATM and ATR, three key biomarkers for DNA strand breakage repair, were significantly increased in PFOA-exposed mice testes. Importantly, levels of 8-OHdG, a classic marker of DNA oxidative damage, was remarkable upregulated in PFOA-exposed mice sperm. Our findings provide new evidence that PFOA decreases acrosome reaction and increases DNA oxidative damage by impairing the sperm head shaping in mice.