Transgenerational Transcriptomic and DNA Methylome Profiling of Mouse Fetal Testicular Germline and Somatic Cells after Exposure of Pregnant Mothers to Tributyltin, a Potent Obesogen.
Transgenerational Transcriptomic and DNA Methylome Profiling of Mouse Fetal Testicular Germline and Somatic Cells after Exposure of Pregnant Mothers to Tributyltin, a Potent Obesogen.
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DOI：
10.3390/metabo12020095
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发表时间：
2022-01-20
期刊：
影响因子：
4.1
通讯作者：
Shioda T
中科院分区：
文献类型：
--
作者：
Shioda K;Odajima J;Blumberg B;Shioda T
三丁基锡（TBT）等致肥剂是一种异生物质化合物，部分通过扭曲脂质代谢的正常平衡来促进肥胖。在直接接触三丁基锡化合物的后代（F1和F2代）以及从未接触过的后代（F3代及以后）中都可以观察到三丁基锡化合物的致肥效应。为了解决三丁基锡化合物暴露对生殖细胞的影响，我们暴露怀孕的转基因OG 2小鼠母鼠（F0），专门表达绿色荧光蛋白在生殖细胞，环境相关剂量的三丁基锡化合物或二甲基亚砜在整个妊娠期通过饮用水。当喂食高脂肪饮食时，TBT暴露的F0母鼠的F3雄性后代（TBT-F3）比DMSO-F3雄性积累了更多的体脂。TBT-F3雄性也比DMSO-F3雄性损失更多的体液和瘦肉成分。在TBT-F1（而不是TBT-F3）E18.5胎儿睾丸的体细胞中，参与转录调控或间充质分化的基因表达上调，并且在TBT-F1体细胞中启动子相关的CpG岛高度甲基化。F0暴露于三丁基锡化合物不影响F1或F3胎儿睾丸细胞中蛋白质编码基因的总体mRNA表达;然而，F1和F3中内源性逆转录病毒亚组的表达受到显著影响。我们推断TBT可能直接靶向F1睾丸中的睾丸体细胞，以不可逆地影响生殖细胞和体细胞中内源性逆转录病毒的表观遗传抑制。
Obesogens such as tributyltin (TBT) are xenobiotic compounds that promote obesity, in part by distorting the normal balance of lipid metabolism. The obesogenic effects of TBT can be observed in directly exposed (F1 and F2 generations) and also subsequent generations (F3 and beyond) that were never exposed. To address the effects of TBT exposure on germ cells, we exposed pregnant transgenic OG2 mouse dams (F0), which specifically express EGFP in germline cells, to an environmentally relevant dose of TBT or DMSO throughout gestation through drinking water. When fed with a high-fat diet, F3 male offspring of TBT-exposed F0 dams (TBT-F3) accumulated much more body fat than did DMSO-F3 males. TBT-F3 males also lost more body fluid and lean compositions than did DMSO-F3 males. Expression of genes involved in transcriptional regulation or mesenchymal differentiation was up-regulated in somatic cells of TBT-F1 (but not TBT-F3) E18.5 fetal testes, and promoter-associated CpG islands were hyper-methylated in TBT-F1 somatic cells. Global mRNA expression of protein-coding genes in F1 or F3 fetal testicular cells was unaffected by F0 exposure to TBT; however, expression of a subset of endogenous retroviruses was significantly affected in F1 and F3. We infer that TBT may directly target testicular somatic cells in F1 testes to irreversibly affect epigenetic suppression of endogenous retroviruses in both germline and somatic cells.
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DOI：
10.3390/ijerph18137170
发表时间：
2021-07-04
影响因子：
--
作者：
Pinos H;Carrillo B;Merchán A;Biosca-Brull J;Pérez-Fernández C;Colomina MT;Sánchez-Santed F;Martín-Sánchez F;Collado P;Arias JL;Conejo NM
通讯作者：
Conejo NM
影响因子：
5.2
作者：
Mohajer N;Joloya EM;Seo J;Shioda T;Blumberg B
通讯作者：
Blumberg B
影响因子：
4.8
作者：
Grun, Felix;Blumberg, Bruce
通讯作者：
Blumberg, Bruce
影响因子：
24
作者：
Coutinho, Thais;Goel, Kashish;Lopez-Jimenez, Francisco
通讯作者：
Lopez-Jimenez, Francisco
影响因子：
16.6
作者：
Pastor, William A.;Stroud, Hume;Nee, Kevin;Liu, Wanlu;Pezic, Dubravka;Manakov, Sergei;Lee, Serena A.;Moissiard, Guillaume;Zamudio, Natasha;Bourc'his, Deborah;Aravin, Alexei A.;Clark, Amander T.;Jacobsen, Steven E.
通讯作者：
Jacobsen, Steven E.