关键词: DEHP Methylation Oxidative stress Soybean isoflavones Testicular injury

Mesh : Male Animals Rats, Sprague-Dawley Testis / drug effects metabolism Diethylhexyl Phthalate / toxicity Glycine max / chemistry Rats Insulin-Like Growth Factor I / metabolism genetics Superoxide Dismutase / metabolism genetics Glutathione Peroxidase / metabolism genetics Isoflavones / pharmacology Glutathione Peroxidase GPX1 RNA, Messenger / metabolism genetics DNA Methylation / drug effects Protective Agents / pharmacology

来  源:   DOI:10.1016/j.cbi.2021.109569   PDF(Sci-hub)

Abstract:
As one of the most important members of Phthalate esters (PAEs), di-(2-ethylhexyl) phthalate (DEHP) is widely used in plastics and known as a male reproductive toxicant. Many studies have shown that soybean isoflavones (SI) can rescue the testicular injury caused by DEHP, but the underlying mechanism is unknown. Because methylation is one of the most important mechanisms for maintaining normal biological functions, we studied whether methylation is involved in testicular injury induced by DEHP and whether SI could counter testicular impairment in peripubertal male Sprague Dawley rats. Compared with the control group, we found that the mRNA levels of testicular Sod2, Gpx1, and Igf-1 significantly decreased in the 900 mg/kg DEHP group (DEHP\' group) (P < 0.01); however, in the DEHP + SI group, the mRNA levels of the genes obviously increased compared with the DEHP\' group (P < 0.01). Simultaneously, the methylation level changes of testicular Sod2, Gpx1, and Igf-1 were similar to the mRNA levels (P < 0.01). Therefore, DEHP may affect testis and leydig cells via inducing methylation of Sod2, Gpx1, and Igf-1, and SI may rescue the impairments at the methylation level. In summary, SI is supposed to be used in DEHP-induced testicular injury treatment.
摘要:
作为邻苯二甲酸酯(PAEs)的重要成员之一,邻苯二甲酸二(2-乙基己基)酯(DEHP)广泛用于塑料中并且被称为男性生殖毒物。许多研究表明,大豆异黄酮(SI)可以挽救DEHP引起的睾丸损伤,但潜在的机制是未知的。因为甲基化是维持正常生物学功能的最重要机制之一,我们研究了甲基化是否与DEHP诱导的睾丸损伤有关,以及SI是否可以对抗青春期雄性SpragueDawley大鼠的睾丸损伤。与对照组相比,我们发现900mg/kgDEHP组(DEHP组)睾丸Sod2,Gpx1和Igf-1的mRNA水平显着降低(P<0.01)。在DEHP+SI组中,与DEHP组相比,这些基因的mRNA水平明显升高(P<0.01)。同时,睾丸Sod2、Gpx1和Igf-1的甲基化水平变化与mRNA水平相似(P<0.01)。因此,DEHP可能通过诱导Sod2,Gpx1和Igf-1的甲基化影响睾丸和睾丸间质细胞,而SI可能在甲基化水平上挽救损伤。总之,SI被认为可用于DEHP诱导的睾丸损伤治疗。
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