Vitamin C supplementation rescued meiotic arrest of spermatocytes in Balb/c mice exposed to BDE-209

Deca-brominated diphenyl ether (BDE-209) is a ubiquitous industrial chemical as brominated flame retardant (BFRs). Exposure to BDE-209 has been clearly associated with male reproductive disorders. However, the meiotic arrest mechanism of spermatocytes exposed to BDE-209 is still unclear. The present work aimed to explore the protective effect of vitamin C on BDE-209-induced meiotic arrest of spermatocytes and its possible mechanism. Vitamin C (100 mg/kg BW) was administered to BDE-209-exposed (80 mg/kg BW) male Balb/c mice once daily by intraperitoneal injection for 2 weeks. Our results showed that vitamin C played male reproductive protection effects as showed by attenuated BDE-209-induced testicular damage, and reduced sperm abnormality rate. Vitamin C also attenuated BDE-209-induced increase in SOD and MDA in testes and GC-2 spd cells. Moreover, vitamin C promoted meiotic prophase in BDE-209-induced mice, with suppressed gamma-H2AX, restored DMC1, RAD51, and crossover marker MLH1 levels, and prevented BDE-209-induced DNA impairment. In addition, vitamin C supplementation also interfered with BDE-209-induced upregulation of testicular H3K4me3 through inhibition of KDM5s capacity and decreasing ferrous ion concentration. Furthermore, ferrous sulfate pretreat-ment could partially restore the expression of H3K4me3 via maintaining the concentration of ferrous ions. Taken together, vitamin C exerts a potential therapeutic agent for preventing BDE-209-induced reproductive toxicity with meiotic arrest, which is attributed to its antioxidant and electron donor properties, as well as, modulation of ferrous ion levels and demethylation of H3K4me3.