Yang Rong, Wang Yi-Mei, Zhang Li-Shi, Zhang Li, Zhao Zeng-Ming, Zhao Jun, Peng Shuang-Qing
Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China.
West China School of Public Health, Sichuan University, Chengdu 610041, China.
Toxins (Basel). 2015 Nov 9;7(11):4668-83. doi: 10.3390/toxins7114668.
Growing evidence has revealed the deleterious influence of environmental and food contaminants on puberty onset and development in both animals and children, provoking an increasing health concern. T-2 toxin, a naturally-produced Type A trichothecene mycotoxin which is frequently found in cereal grains and products intended for human and animal consumption, has been shown to impair the reproduction and development in animals. Nevertheless, whether this trichothecene mycotoxin can disturb the onset of puberty in females remains unclear. To clarify this point, infantile female rats were given a daily intragastric administration of vehicle or 187.5 μg/kg body weight of T-2 toxin for five consecutive days from postnatal day 15 to 19, and the effects on puberty onset were evaluated in the present study. The results revealed that the days of vaginal opening, first dioestrus, and first estrus in regular estrous cycle were delayed following prepubertal exposure to T-2 toxin. The relative weights of reproductive organs uterus, ovaries, and vagina, and the incidence of corpora lutea were all diminished in T-2 toxin-treated rats. Serum levels of gonadotropins luteinizing hormone, follicle-stimulating hormone, and estradiol were also reduced by T-2 toxin treatment. The mRNA expressions of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary GnRH receptor displayed significant reductions following exposure to T-2 toxin, which were consistent with the changes of serum gonadotropins, delayed reproductive organ development, and delayed vaginal opening. In conclusion, the present study reveals that prepubertal exposure to T-2 toxin delays the onset of puberty in immature female rats, probably by the mechanism of disturbance of hypothalamic-pituitary-gonadal (HPG) axis function. Considering the vulnerability of developmental children to food contaminants and the relative high level of dietary intake of T-2 toxin in children, we think the findings of the present study provide valuable information for the health risk assessment in children.
越来越多的证据表明,环境和食物污染物对动物和儿童的青春期启动及发育具有有害影响,引发了越来越多的健康担忧。T-2毒素是一种天然产生的A类单端孢霉烯族霉菌毒素,常见于谷物及供人类和动物食用的产品中,已被证明会损害动物的生殖和发育。然而,这种单端孢霉烯族霉菌毒素是否会干扰雌性动物的青春期启动仍不清楚。为阐明这一点,本研究从出生后第15天至19天,对幼龄雌性大鼠连续5天每日灌胃给予溶剂或187.5μg/kg体重的T-2毒素,并评估其对青春期启动的影响。结果显示,青春期前暴露于T-2毒素后,阴道开口、首次动情间期和规律发情周期中的首次发情天数均延迟。T-2毒素处理的大鼠生殖器官子宫、卵巢和阴道的相对重量以及黄体发生率均降低。T-2毒素处理还降低了血清促性腺激素促黄体生成素、促卵泡生成素和雌二醇的水平。暴露于T-2毒素后,下丘脑促性腺激素释放激素(GnRH)和垂体GnRH受体的mRNA表达显著降低,这与血清促性腺激素的变化、生殖器官发育延迟和阴道开口延迟一致。总之,本研究表明,青春期前暴露于T-2毒素会延迟未成熟雌性大鼠的青春期启动,可能是通过干扰下丘脑-垂体-性腺(HPG)轴功能的机制。考虑到发育中的儿童对食物污染物的易感性以及儿童饮食中T-2毒素的相对高摄入量,我们认为本研究结果为儿童健康风险评估提供了有价值的信息。