Adolescence is a sensitive period for acrylamide-induced sex hormone disruption: Evidence from NHANES populations and experimental mice.
Adolescence is a sensitive period for acrylamide-induced sex hormone disruption: Evidence from NHANES populations and experimental mice.
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DOI：
10.1016/j.ecoenv.2022.114413
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发表时间：
2022-12
影响因子：
6.8
通讯作者：
Yongquan Yu;Di Zhang;Jiayi Xu;Daiwei Zhang;Liu Yang;Rong Xia;Shou-Lin Wang
中科院分区：
文献类型：
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作者：
Yongquan Yu;Di Zhang;Jiayi Xu;Daiwei Zhang;Liu Yang;Rong Xia;Shou-Lin Wang
丙烯酰胺（AA）在环境和饮食中污染严重。然而，AA和性激素的关联很少被调查，特别是在青少年中，一个特别容易受到性激素干扰的时期。在这项研究中，进行了调查加权的多元线性回归模型，以确定来自2013-2016年国家健康与营养调查（NHANES）波的总计3268名受试者中AA Hb生物标志物[HbAA和缩水甘油胺（HbGA）]与性激素[总睾酮（TT）和雌二醇（E2）]之间的相关性。此外，成年和青春期小鼠用AA处理，以评估AA对性激素的影响并探讨其潜在机制。在所有受试者中，仅在青年（6-19岁）中确定了HbGA和性激素的显著阴性模式，男性TT的最低β为-0.53（95% CI：-0.80至0.26），女性E2的最低β为-0.58（95% CI：-0.93至0.23）。分层分析进一步揭示了青少年中HbGA与性激素之间的显著负相关性，男性TT的最低β为-0.58（95%CI：-1.02至0.14），女性E2的最低β为-0.54（95%CI：-1.03至0.04），而儿童和青少年晚期之间无显著差异。在小鼠中，AA处理的青春期小鼠的TT和E2水平显著降低，但成年小鼠的TT和E2水平没有降低。AA干扰下丘脑-垂体-性腺轴（HPG）基因表达，诱导下丘脑促性腺激素释放激素（GnRH）神经元凋亡，降低青春期小鼠血清和下丘脑GnRH水平。本研究提示AA可通过损伤青春期GnRH神经元和破坏HPG轴而降低TT和E2水平，表现为严重的内分泌紊乱。我们的研究结果强化了这样一种观点，即青春期是AA诱导性激素紊乱的脆弱阶段。
Acrylamide (AA) is widely contaminated in environment and diet. However, the association of AA and sex hormones has rarely been investigated, especially in adolescents, a period of particular susceptibility to sex hormone disruption. In this study, survey-weighted multivariate linear regression models were conducted to determine the association between AA Hb biomarkers [HbAA and glycidamide (HbGA)] and sex hormones [total testosterone (TT) and estradiol (E2)] in a total of 3268 subjects from National Health and Nutrition Examination Survey (NHANES) 2013–2016 waves. Additionally, adult and pubertal mice were treated with AA to assess the effect of AA on sex hormones and to explore the potential mechanisms. Among all the subjects, significant negative patterns for HbGA and sex hormones were identified only in youths (6–19 years old), with the lowest β being − 0.53 (95% CI: −0.80 to −0.26) for TT in males and − 0.58 (95% CI: −0.93 to −0.23) for E2in females. Stratified analysis further revealed significant negative associations between HbGA and sex hormones in adolescents, with the lowest β being − 0.58 (95% CI: −1.02 to −0.14) for TT in males and − 0.54 (95% CI: −1.03 to −0.04) for E2in females, while there were no significant differences between children or late adolescents. In mice, the levels of TT and E2were dramatically reduced in AA-treated pubertal mice but not in adult mice. AA disturbed the expression of genes in the hypothalamic–pituitary–gonadal (HPG) axis, induced apoptosis of hypothalamus-produced gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus and reduced serum and hypothalamic GnRH levels in pubertal mice. Our study indicates AA could reduce TT and E2levels by injuring GnRH neurons and disrupting the HPG axis in puberty, which manifested as severe endocrine disruption on adolescents. Our findings reinforce the idea that adolescence is a vulnerable stage in AA-induced sex hormone disruption.