FMR1基因敲除对雌性小鼠生殖功能的影响

Influence of FMR1 gene knockout on the reproduction of female mice

目的利用FMR1基因敲除小鼠,研究FMR1基因缺失对雌性小鼠生殖功能的影响,并对其影响机制进行探讨。方法将成年的KO纯合子、KO杂合子、WT雌鼠分别和成年的WT雄鼠合笼,观察合笼时间及产仔数;随机取10周的上述3种基因型雌鼠,HE染色观察卵巢形态;免疫组化测定NPY和GABA在下丘脑的分布,Image Pro Plus 6.0分析平均光密度值;ELISA测定血清NPY水平。结果 3组小鼠中,KO纯合子雌鼠的产仔数少于WT雌鼠(6.39±2.30)、(7.60±2.69)和(8.00±1.88);KO纯合子雌鼠的卵泡总数少于WT雌鼠(36.00±5)、(39.33±7.87)和(45.45±7.85);KO纯合子雌鼠下丘脑NPY的表达弱于WT雌鼠(0.27±0.016)、(0.29±0.04)和(0.31±0.041);血清NPY及下丘脑GABA的表达三组间差异均无显著性(P>0.05)。结论FMR1基因敲除可导致雌鼠生育功能下降,FMR1基因可能是通过下调NPY的表达来降低其生殖功能的。

To investigate the influence of fragile x mental retardation-1 gene on the reproduction of female mice. 【Methods】Adult FMR1 knockout homozygous,FMR1 knockout heterozygous,wild type（WT） female mice were mated with adult male mice. The time of childbirth, the number of litters were counted. 10 weeks FMR1 knockout homozygous,FMR1 knockout heterozygous, WT female mice were selected, collecting the ovaries, hypothalamus and serum. HE staining was performed to observe the morphology of ovaries and count the follicles; The expression of NPY and GABA in hypothalamus were tested by immunohistochemistry, mean optical density（MOD） of NPY and GABA were analyzed by Image Pro Plus 6.0; Serum NPY concentrations were measured by ELISA.【Results】There were no significant differences in the time of childbirth in these three groups（P 0.05）; Litter size of FMR1 knockout homozygous female mice were significantly lower than the WT female mice（6.39±2.30, 7.60±2.69, 8.00±1.88）; No obvious pathological differences in ovaries were found among the three groups; Number of follicles of FMR1 knockout homozygous female mice was significantly lower than the WT female mice（36.00±5.6, 39.33±7.87,45.45±7.85）; The expression of NPY in hypothalamus of FMR1 knockout homozygous female mice was weaken than WT female mice（0.27 ±0.016, 0.29 ±0.04, 0.31±0.041）; Serum NPY concentrations of these mice had no significant differences（P 0.05）; MOD of GABA in hypothalamus of the above mice had no statistical significances（P 0.05）. 【Conclusions】FMR1 gene knockout can reduce the reproductive function of female mice; the absence of FMR1 gene may reduce the expression of NPY, this may be one of the mechanisms how FMR1 gene influencing the female reproductive function.