Murine model for congenital CMV infection and hearing impairment.
Murine model for congenital CMV infection and hearing impairment.
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DOI：
10.1186/1743-422x-8-70
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发表时间：
2011-02-15
期刊：
影响因子：
4.8
通讯作者：
Suhua C
中科院分区：
文献类型：
--
作者：
Juanjuan C;Yan F;Li C;Haizhi L;Ling W;Xinrong W;Juan X;Tao L;Zongzhi Y;Suhua C
先天性巨细胞病毒（CMV）感染是引起感音神经性耳聋（SNHL）的主要原因，而SNHL又是先天性CMV感染最常见的后遗症。但其发病机制尚不清楚，目前尚无理想的CMV宫内感染动物模型来研究SNHL的发病机制。我们在妊娠第12.5天将小鼠巨细胞病毒（MCMV）直接注入胎盘，建立了先天性MCMV感染模型。观察胎鼠出生当天的发育情况及MCMV先天感染率。检测28日龄和70日龄仔鼠的听功能、MCMV感染情况及内耳组织学变化。胎盘接种MCMV后，子代的流产率和畸形率均增加，体长、头围和体重均下降。后代的听力水平在出生后28天和70天都有所下降; 70天大的小鼠的听力水平低于28天大的小鼠。在小鼠耳蜗中未观察到显著的炎症变化。MCMV DNA信号主要分布于螺旋神经节神经元和内淋巴区，外淋巴区无信号。神经元数量减少，超微结构改变。随着年龄的增长，神经元数量明显减少，神经元的超微结构损伤更加严重。结果提示，MCMV直接注射胎盘可有效地引起胎儿感染，干扰胎儿宫内发育，胎盘接种本身对子代无明显不良影响。螺旋神经节神经元数量减少和超微结构改变可能是先天性CMV感染所致进行性SNHL的主要原因。
Congenital cytomegalovirus (CMV) infection is the leading cause of sensorineural hearing loss (SNHL), and SNHL is the most frequent sequela of congenital CMV infection. But the pathogenic mechanism remains unknown, and there is no ideal CMV intrauterine infection animal model to study the mechanisms by which SNHL develops. We established the congenital murine cytomegalovirus (MCMV) infection model by directly injecting the virus into the placenta on day 12.5 of gestation. Then, we observed the development and the MCMV congenital infection rate of the fetuses on the day they were born. Furthermore, we detected the auditory functions, the conditions of the MCMV infection, and the histological change of the inner ears of 28-day-old and 70-day-old offspring. Both the fetal loss rate and the teratism rate of offspring whose placentas were inoculated with MCMV increased, and their body length, head circumference, and weight decreased. The hearing level of offspring both decreased at both 28- and 70-days post birth; the 70-day-old mice developed lower hearing levels than did the 28-day old mice. No significant inflammatory changes in the cochleae of the mice were observed. MCMV DNA signals were mainly detected in the spiral ganglion neurons and the endolymph area, but not in the perilymph area. The number of neurons decreased, and their ultrastructures changed. Moreover, with age, the number of neurons dramatically decreased, and the ultrastructural lesions of neurons became much more severe. The results suggest that the direct injection of MCMV into the placenta may efficiently cause fetal infection and disturb the intrauterine development of the fetus, and placental inoculation itself has no obvious adverse effects on offspring. The reduction in the number of spiral ganglion neurons and the ultrastructural lesions of the neurons may be the major cause of congenital CMV infection-induced progressive SNHL.