Exposure to low-dose bisphenol A impairs meiosis in the rat seminiferous tubule culture model: a physiotoxicogenomic approach.
Exposure to low-dose bisphenol A impairs meiosis in the rat seminiferous tubule culture model: a physiotoxicogenomic approach.
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DOI：
10.1371/journal.pone.0106245
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Prat O
中科院分区：
文献类型：
--
作者：
Ali S;Steinmetz G;Montillet G;Perrard MH;Loundou A;Durand P;Guichaoua MR;Prat O
双酚A（BPA）是世界上分布最广的化学物质之一，被怀疑是导致男性生殖障碍的原因。然而，其对精子发生作用的分子模式尚不清楚。这项工作结合了生理学和毒理基因组学，以确定BPA影响减数分裂时间和诱导生殖细胞异常的机制。我们使用了大鼠生精小管培养模型，模仿体内成年大鼠的情况。向培养基中加入BPA（1 nM和10 nM）。在相同的暴露时间（第8、14和21天）对相同的培养物进行转录组学和减数分裂研究。使用pangenomic大鼠微阵列进行转录组学。用抗SCP 3抗体进行免疫细胞化学。基因表达分析表明，差异表达转录本的总数是时间依赖性的，但不依赖于剂量。我们专注于120个基因直接参与第一次减数分裂前期，维持免疫细胞化学。62个基因直接参与配对和重组，其中一些具有高倍数变化。免疫细胞化学表明，在BPA的存在下，减数分裂进程的改变，增加细线期和双线期精母细胞的百分比和部分减数分裂阻滞在粗线期检查点。在减数分裂前期的所有阶段都观察到形态异常。普遍的异常是总不联会和凋亡。转录组学分析支持免疫细胞学观察。我们发现，低剂量的BPA改变了许多基因的表达，特别是那些参与生殖系统，并严重损害减数分裂前期的关键事件，导致部分逮捕大鼠曲细精管培养的减数分裂。
Bisphenol A (BPA) is one of the most widespread chemicals in the world and is suspected of being responsible for male reproductive impairments. Nevertheless, its molecular mode of action on spermatogenesis is unclear. This work combines physiology and toxicogenomics to identify mechanisms by which BPA affects the timing of meiosis and induces germ-cell abnormalities. We used a rat seminiferous tubule culture model mimicking the in vivo adult rat situation. BPA (1 nM and 10 nM) was added to the culture medium. Transcriptomic and meiotic studies were performed on the same cultures at the same exposure times (days 8, 14, and 21). Transcriptomics was performed using pangenomic rat microarrays. Immunocytochemistry was conducted with an anti-SCP3 antibody. The gene expression analysis showed that the total number of differentially expressed transcripts was time but not dose dependent. We focused on 120 genes directly involved in the first meiotic prophase, sustaining immunocytochemistry. Sixty-two genes were directly involved in pairing and recombination, some of them with high fold changes. Immunocytochemistry indicated alteration of meiotic progression in the presence of BPA, with increased leptotene and decreased diplotene spermatocyte percentages and partial meiotic arrest at the pachytene checkpoint. Morphological abnormalities were observed at all stages of the meiotic prophase. The prevalent abnormalities were total asynapsis and apoptosis. Transcriptomic analysis sustained immunocytological observations. We showed that low doses of BPA alter numerous genes expression, especially those involved in the reproductive system, and severely impair crucial events of the meiotic prophase leading to partial arrest of meiosis in rat seminiferous tubule cultures.
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影响因子：
6.1
作者：
Guichaoua, MR;Perrin, J;Grillo, JM
通讯作者：
Grillo, JM
影响因子：
2.7
作者：
Godet, Murielle;Sabido, Odile;Durand, Philippe
通讯作者：
Durand, Philippe
DOI：
10.1016/0027-5107(88)90020-6
发表时间：
1988-10-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
ALLEN, JW;GIBSON, JB;MOSES, MJ
通讯作者：
MOSES, MJ
DOI：
10.1016/j.mrgentox.2007.10.014
发表时间：
2008-03-12
影响因子：
1.9
作者：
Eichenlaub-Ritter, Ursula;Vogt, Edgar;Parry, Jim
通讯作者：
Parry, Jim
影响因子：
3.3
作者：
Iida, H;Maehara, K;Yamada, F
通讯作者：
Yamada, F