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.
Keywords: Arsenic; H3K14ac; Spermatogenesis; Steroidogenic regulatory enzymes; Testosterone production.
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