T-2毒素对小鼠睾丸间质细胞的毒性分子机制

T-2 toxin is one of the strongest toxicity among trichothecene mycotoxins, which exists widely in food crops such as corn, wheat, barley, rice and their semi-finished products.It is the most dangerous source of pollution as to feed and food in nature, leading to reduce the male fertility obviously, which makes studying the underlying mechanism to improve the male fertility critical. Our study aims at establishing a stable testicular mesenchymal cells culturing system via RNA interference induced by lentivirus carrier and gene overexpressing technology ,by which to research the mechanism of T-2 toxins in regulating interstitial cell proliferation, apoptosis and hormone secretion after the expression inhibition or increase of p450scc, StAR or 3 beta HSD gene; On the basis, using molecular biology research method such as yeast double hybridization and immune deposits chromatin analysis (ChIP), we further study the relationships among p450scc, StAR or 3 beta HSD and T-2 toxins and their molecular regulation mechanism between testosterone secretion genes. Not only our findings have important academic value, but also provide certain theoretical and experimental basis for reproductive regulating technology, the treatment of reproductive endocrine disease and the development of related drugs.

T-2毒素是单端孢霉烯族真菌毒素中毒性最强的一种，广泛存在于玉米、小麦、大麦、水稻等粮食作物及其半成品中，是自然界存在的最危险的饲料及食品污染源之一，可导致雄性生育能力明显下降，研究其作用机制进而改善雄性生育能力已迫在眉睫。本课题拟通过慢病毒载体介导的RNA干扰和基因超表达技术建立稳定的睾丸间质细胞（系）培养模型，研究T-2毒素在p450scc、StAR或3β-HSD基因表达抑制或增加后对间质细胞增殖、凋亡及激素分泌的调控机制；在此基础上，利用酵母双杂交和染色质免疫沉淀分析（ChIP）等分子生物生物学方法研究p450scc、StAR或3β-HSD和T-2毒素的相互作用关系，及其与睾酮分泌调控基因间的分子作用机制。本研究结果不仅具有重要的学术意义，而且将为生殖调控技术和生殖内分泌疾病治疗与相关药物的研发等提供一定的理论和实验依据。

T-2毒素是单端孢霉烯族真菌毒素中毒性最强的一种，广泛存在于玉米、小麦、大麦、水稻等粮食作物及其半成品中，是自然界存在的最危险的饲料及食品污染源之一，其对人类的危害及作用机制越来越受到人们的关注。因此，本项目以雄性小鼠和睾丸间质细胞为研究对象，采用体内和体外相结合的方法重点研究了T-2毒素对雄性小鼠生殖系统的影响和作用机制。结果表明，T-2毒素通过抑制小鼠睾丸间质细胞的分泌功能，造成其精液品质及生育能力严重下降；T-2毒素抑制小鼠睾丸间质细分泌功能与3β-HSD、P450scc及StAR基因的转录和表达水平降低密切相关，也与T-2毒素引起的小鼠睾丸间质细胞凋亡密不可分。本研究结果不仅具有重要的学术意义，而且将为生殖调控技术和生殖内分泌疾病治疗与相关药物的研发等提供一定的理论和实验依据。