Sodium arsenite impairs sperm quality via downregulating the ZMYND15 and ZMYND10.

Zinc finger MYND-type containing 15 (ZMYND15) has been documented to play important roles in spermatogenesis, and mutants contribute to recessive azoospermia, severe oligozoospermia, non-obstructive azoospermia, teratozoospermia, even male infertility. ZMYND10 is involved in sperm motility. Whether environmental pollutants impair male fertility via regulating the expression of ZMYND15 and ZMYND10 has not been studied. Arsenic exposure results in poor sperm quality and male infertility. In order to investigate whether arsenic-induced male reproductive toxicity is related to the expression of ZMYND15, ZMYND10 and their target genes, we established a male rat model of sodium arsenite exposure-induced reproductive injury, measured sperm quality, serum hormone levels, mRNA and protein expressions of intratesticular ZMYND15 and ZMYND10 as well as their target genes. The results showed that, in addition to the increased mRNA expression of Tnp1, sodium arsenite exposure reduced sperm quality, serum hormone levels, and mRNA and protein expression of intratesticular ZMYND15 and ZMYND10 and their target genes in male rats compared with the control group (p < .05). Therefore, our study first showed that the environmental pollutant arsenic impairs sperm quality in male rats by reducing the expression of ZMYND10 and ZMYND15 and their regulatory genes, which provides a possible diagnostic marker for environmental pollutants-induced male infertility.

Selenium Improves Arsenic-Induced Male Reproductive Dysfunction by Regulating H3K14ac Level.

Arsenic exposure has been known to be associated with male reproduction injury. Exploring the antidote of arsenic and ascertaining proper dose of antidote are important for detoxifying the male reproductive toxicity of arsenic. Selenium, which is essential for the male reproduction and spermatogenesis, can alleviate the toxicity of many environmental toxins, such as metals, and fluoride (F). Selenium relieves arsenic-induced reductions in spermatogenesis index and testicular function marker enzymes via promoting the antioxidative ability of rats. Our previous study has found that arsenic can induce male reproductive toxicity by affecting the level of H3K14ac in the testis, so we further investigate whether selenium can antagonize arsenic-induced male reproductive toxicity through the H3K14ac pathway and ascertain the appropriate dose of selenium. The results show that selenium intervention reduces the accumulation of arsenic in rat testis probably attributing to promote the excretion of arsenic from rat, then improves the testis injury induced by arsenic. Selenium intervention enhances sperm quality, testosterone level, and expression of steroidogenic genes by regulating H3K14ac level and expression of its associated enzymes (KAT2A, BAZ2A, and HDAC6), and thus alleviates the male reproductive toxicity of arsenic, and the proper dose of Se for mitigating arsenic male reproductive toxicity is 1 mg/kg.

Sodium arsenite exposure enhances H3K14 acetylation and impairs male spermatogenesis in rat testes.

Histone modifications play important roles in the epigenetic regulation of spermatogenesis via mediating gene transcription. Steroidogenic regulatory enzymes control testosterone biosynthesis, which are essential for spermatogenesis. Arsenic exposure inhibits the expression of steroidogenic genes by significantly increasing tri-methylation of H3K9 (H3K9me3) level in rat testis, finally diminishes testosterone release and lowers the rat sperm quality. Acetylation of H3K14 (H3K14ac) is associated with testosterone production and spermatogenesis. Co-occurrence of H3K9me3/H3K14ac has been identified previously by mass spectrometry in histone H3 isolated from different human cell types. H3K9me3/H3K14ac dually marked regions are in a poised inactive state to inhibit the gene expression. Whereas, whether inorganic arsenic exposure affects spermatogenesis and steroidogenic regulatory enzymes via mediating H3K14ac level has not been studied. Thereupon, the male Sprague-Dawley (SD) rats were exposed to (NaAsO2) for 6 weeks, then the sperm density and motility, testosterone level in serum, arsenic in rat testis were detected. mRNA expression of steroidogenic regulatory enzymes Star, Cyp11a1, Hsd3b and Hsd17b were determined by RT-PCR. H3K14ac level and the expression of histone acetylases of H3K14 (KAT2A and EP300), histone deacetylases of H3K14 (HDAC6 and HDAC3), the reader of H3K14ac (BAZ2A) were determined. The results suggested arsenic enhances H3K14ac in rat testis, which was associated with repression of steroidogenic regulatory genes expression, further reduced testosterone production, and impaired the spermatogenesis.