As3MT-mediated SAM consumption, which inhibits the methylation of histones and LINE1, is involved in arsenic-induced male reproductive damage. (15th November 2022)

• Record Type: Journal Article
• Authors: Wu, Lu; Li, Han; Ye, Fuping; Wei, Yongyue; Li, Wenqi; Xu, Yuan; Xia, Haibo; Zhang, Jingshu; Guo, Lianxian; Zhang, Guiwei; Chen, Feng; Liu, Qizhan
• Is Part Of: Environmental pollution. Volume 313(2022)
• Publication Date: 2022-11-15
• Subjects: Arsenic -- As3MT -- DSBs repair -- Methylation modification -- Male reproductive damage; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2022.120090
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Studies have demonstrated that arsenic (As) induces male reproductive injury, however, the mechanism remains unknown. The high levels of arsenic (3) methyltransferase (As3MT) promote As-induced male reproductive toxicity. For As-exposed mice, the germ cells in seminiferous tubules and sperm quality were reduced. Exposure to As caused lower S-adenosylmethionine (SAM) and 5-methylcytosine (5 mC) levels, histone and DNA hypomethylation, upregulation of long interspersed element class 1 (LINE1, or L1), defective repair of double-strand breaks (DSBs), and the arrest of meiosis, resulting in apoptosis of germ cells and lower litter size. For GC-2spd (GC-2) cells, As induced apoptosis, which was prevented by adding SAM or by reducing the expression of As3MT. The levels of LINE1, affected by SAM content, were involved in As-induced apoptosis. Furthermore, folic acid (FA) and vitamin B12 (VB12 ) supplements restored SAM, 5 mC, and LINE1 levels and blocked impairment of spermatogenesis and testes and lower litter size. Exposed to As, mice with As3MT knockdown showed less impairment of spermatogenesis and testes and greater litter size compared to As-exposed wild-type (WT) mice. Thus, the high As3MT levels induced by As consume SAM and block histone and LINE1 DNA methylation, elevating LINE1 expression and evoking impairment of spermatogenesis, which causes male reproductive damage. Overall, we have found a mechanism for As-induced male reproductive damage, which provides biological insights into the alleviation of reproductive injury induced by environmental factors. Graphical abstract: Image 1 Highlights: Exposure to As causes male reproductive damage via As3MT-mediated SAM consumption. Low levels of SAM induced by As block methylation modifications of histones and LINE1. FA and VB12 block As-induced male reproductive damage via providing SAM. Knockdown of As3MT blocks male reproductive damage through reducing SAM consumption.