Gamma-irradiation increased meiotic crossovers in mouse spermatocytes

Gamma-irradiation increased meiotic crossovers in mouse spermatocytes
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DOI:
10.1093/mutage/ger038
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发表时间:
2011-11-01
期刊:
影响因子:
2.7
通讯作者:
Shi, Qinghua
Shi, Qinghua
中科院分区:
医学4区
文献类型:
--
作者:
Cai, Xin;Li, Jianhua;Shi, Qinghua

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在小鼠中,错配修复蛋白MLH 1的免疫荧光灶的发生与交叉的发生密切相关,如遗传学检测的,MLH 1灶几乎代表了所有预期的交叉位置。为了研究γ射线照射对小鼠精母细胞减数分裂交叉的影响,雄性小鼠在减数分裂前期的不同亚阶段接受全身γ射线照射,并通过可视化和定量免疫荧光MLH 1病灶来分析联会复合体(SC)上的交叉。照射后24和48 h,随着照射剂量从0、1.5、3-6戈伊梯度增加,在合子期晚期-粗线期早期,每个精母细胞的MLH 1总灶数呈剂量依赖性增加。此外,在前细线期-细线期的照射仍然导致暴露后120小时分析的精母细胞中减数分裂交叉的显著剂量依赖性增加。在进一步分析中,每个细胞总MLH 1病灶数量的这些剂量依赖性增加归因于具有0个MLH 1病灶的常染色体SC的显著剂量依赖性减少,以及具有2个MLH 1病灶的常染色体SC的剂量依赖性增加和具有XY二价MLH 1病灶的细胞百分比。MLH 1集中在假常染色体区域(PAR)的细胞数量增加,可能表明辐照细胞的减数分裂进程延迟。尽管在暴露后24、48或120 h,随着辐射剂量的梯度增加,每个细胞的MLH 1病灶总数呈剂量依赖性显著增加,但与对照组相比,这些增加是轻微的。这表明交叉形成受到严格控制(至少在MLH 1病灶数量方面)。辐射诱导DNA损伤修复、不依赖于DNA损伤的细胞反应和减数分裂交叉稳态等机制将是未来研究的重点。
In mice, the occurrence of immunofluorescent foci for mismatch repair protein MLH1 correlates closely with the occurrence of crossovers, as detected genetically, and MLH1 foci represent virtually all prospective crossover positions. To examine the effects of gamma-irradiation on meiotic crossovers in mouse spermatocytes, male mice were subjected to whole-body gamma-irradiation at different sub-stages of meiotic prophase and crossovers on synaptonemal complexes (SCs) were analysed by visualising and quantifying the immunofluorescent MLH1 foci. At both 24 and 48 h after exposure, significant dose-dependent increases in the number of total MLH1 foci per spermatocyte were observed at late zygotene-early pachytene with the gradient increase of radiation dose from 0, 1.5, 3-6 Gy. Furthermore, irradiation at preleptotene-leptotene still led to significant dose-dependent increased meiotic crossovers in the spermatocytes analysed 120 h after exposure. In further analysis, these dose-dependent increases in the number of total MLH1 foci per cell were attributed to significant dose-dependent decreases in autosomal SCs with 0 MLH1 focus, and the dose-dependent increases in autosomal SCs with 2 MLH1 foci and the percentage of cells with MLH1 focus on XY bivalent. The increased number of cells with an MLH1 focus on the pseudoautosomal regions (PARs) may indicate that there is a delay in meiotic progression in the irradiated cells. Although significant dose-dependent increases in the number of total MLH1 foci per cell were examined 24, 48 or 120 h after exposure with the gradient increase of radiation doses, these increases were mild compared to the control groups. This suggests that there is tight control of crossover formation (at least with respect to MLH1 foci number). The mechanisms underlying irradiation-induced DNA lesion repair, cellular responses independent of DNA damage and meiotic crossover homeostasis in mammals will be the subjects of future study.