手機(jī)版
You are what your grandmother ate, potentially, but maybe not what your great grandmother consumed. A study in mice shows that undernourishment during pregnancy increases the chances that the next two generations will develop obesity and diabetes. But by then the slate is wiped clean.
If the same holds true for humans, it may mean that stressful events in our lives affect our grandchildren's health, but not great-grandchildren.
Environmental stresses cause chemical changes to DNA that turn genes on and off. Many researchers believe that these changes can be passed down through sperm and eggs – a mechanism known as epigenetic inheritance.
Low-calorie diet
For example, studies have linked pregnant mothers that were undernourished during the second world war with gene changes in their children that put them at higher risk of becoming obese or getting cancer. But what happens to later generations is not clear.
To model this effect, Anne Ferguson-Smith at the University of Cambridge and her colleagues fed pregnant mice a diet containing 50 per cent fewer calories than usual from the 12th day of gestation until the birth, which is normally after about 20 days. Offspring were smaller than average and developed diabetes when fed a healthy diet. When the male pups had offspring, they were also at higher risk of becoming diabetic.
The team analysed the sperm of the offspring from the undernourished mothers to see how many genes had had their expression altered by the addition or removal of a methyl group – an epigenetic change. The team found a decrease in methylation in 111 regions of the DNA compared with sperm from mice born to mothers fed a healthy diet.
Unknown mechanism
When these mice, which had normal diets, had pups, however, the methylation patterns disappeared from their offspring's DNA. This was surprising – because the grandpups still proved to be more likely to get diabetes. "It suggests that methylation is a marker but probably not the key mechanism causing the disease," says Ferguson-Smith. She says it is not yet clear what other mechanism might be at work.
She hypothesises that epigenetic inheritance is a short-term adaptation that allows the offspring to be programmed for a stressful environment, but one that can easily be erased if the stressor disappears. "It would make sense to have evolved mechanisms to sense short-term changes in the environment, such that when nutrition became normal again this adaptation wouldn't persist," says Ferguson-Smith.
The team is now investigating whether further generations have an increased risk of developing diabetes to shed some light on how many generations the impact of a parent's diet can last.
參考譯文：
一項(xiàng)小鼠實(shí)驗(yàn)表明，母親孕期營(yíng)養(yǎng)不足會(huì)增高子代和孫代發(fā)生肥胖及患上糖尿病的機(jī)會(huì)，但再下一代的健康將不再受影響。
如果這項(xiàng)結(jié)果對(duì)人類也適用的話，這就可能意味著我們生命中所遭遇的艱難困苦會(huì)影響我們孫輩的健康，但對(duì)我們的重孫輩沒有影響。
環(huán)境壓力能導(dǎo)致DNA發(fā)生化學(xué)變化，使得基因被打開或關(guān)閉。許多研究者相信，這些變化能通過精子或卵子遺傳到下一代——這種機(jī)制稱為“后成的遺傳”或“表觀遺傳”。
喂養(yǎng)
例如，已有研究表明二戰(zhàn)期間一些孕婦的營(yíng)養(yǎng)不良跟她們的孩子的一些基因變化有關(guān)，這些變化會(huì)提高肥胖發(fā)生與罹患癌癥的風(fēng)險(xiǎn)。然而，從她們的孫輩起會(huì)有什么變化，則不得而知。
為了建立研究該種影響的模型，劍橋大學(xué)的Anne Ferguson-Smith和她的同事對(duì)懷孕的小鼠進(jìn)行了喂養(yǎng)實(shí)驗(yàn)。在小鼠妊娠12天后至產(chǎn)仔這段時(shí)間內(nèi)（歷時(shí)約20天）以熱量比正常所需含量低一半的食物進(jìn)行喂養(yǎng)，結(jié)果子代小鼠的體型小于平均水平，并在正常的喂養(yǎng)條件下患上了糖尿病，而且其中的子代雄鼠的兒女們（即營(yíng)養(yǎng)不良雌鼠的孫輩）患糖尿病的風(fēng)險(xiǎn)也提高了。
該研究小組分析了營(yíng)養(yǎng)不良雌鼠的兒孫們的精子DNA，結(jié)果發(fā)現(xiàn)，與母親得到正常喂養(yǎng)的雄鼠的精子DNA相比，前者有111個(gè)區(qū)域發(fā)生了甲基化或去甲基化——一種常見的表觀遺傳學(xué)變化。
機(jī)制不明
然而，在正常喂養(yǎng)的條件下，上述變化（甲基化或去甲基化）從第四代小鼠的DNA中消失了。這一結(jié)果令人驚異，因?yàn)橹钡降谌∈�，它們�(nèi)允歉菀谆继悄虿〉�。Ferguson-Smith說，“這個(gè)結(jié)果暗示，甲基化只是一個(gè)標(biāo)志，但很可能并不是導(dǎo)致糖尿病的關(guān)鍵機(jī)理。”她還說，尚不明確是否另有其他致病機(jī)理。
她猜想，表觀遺傳是一種短期的適應(yīng)性，它使得小鼠后代得以應(yīng)對(duì)逆境，但一旦逆境壓力消失，這種適應(yīng)性也就隨之被清除。“合理的推斷是，它們進(jìn)化出了一些機(jī)制來感知短期的環(huán)境變化，因此當(dāng)小鼠的營(yíng)養(yǎng)供應(yīng)恢復(fù)正常后，這種適應(yīng)性也就不再持續(xù)。”
該研究小組將繼續(xù)研究更多代小鼠患糖尿病的風(fēng)險(xiǎn)是否會(huì)增高，以期探明母親的飲食對(duì)后代健康的影響到底能持續(xù)多少代。
原始來源：http://www.newscientist.com/article/dn25884-famine-puts-next-two-generations-at-risk-of-obesity.html#.VCUYUdyn8ZF
If the same holds true for humans, it may mean that stressful events in our lives affect our grandchildren's health, but not great-grandchildren.
Environmental stresses cause chemical changes to DNA that turn genes on and off. Many researchers believe that these changes can be passed down through sperm and eggs – a mechanism known as epigenetic inheritance.
Low-calorie diet
For example, studies have linked pregnant mothers that were undernourished during the second world war with gene changes in their children that put them at higher risk of becoming obese or getting cancer. But what happens to later generations is not clear.
To model this effect, Anne Ferguson-Smith at the University of Cambridge and her colleagues fed pregnant mice a diet containing 50 per cent fewer calories than usual from the 12th day of gestation until the birth, which is normally after about 20 days. Offspring were smaller than average and developed diabetes when fed a healthy diet. When the male pups had offspring, they were also at higher risk of becoming diabetic.
The team analysed the sperm of the offspring from the undernourished mothers to see how many genes had had their expression altered by the addition or removal of a methyl group – an epigenetic change. The team found a decrease in methylation in 111 regions of the DNA compared with sperm from mice born to mothers fed a healthy diet.
Unknown mechanism
When these mice, which had normal diets, had pups, however, the methylation patterns disappeared from their offspring's DNA. This was surprising – because the grandpups still proved to be more likely to get diabetes. "It suggests that methylation is a marker but probably not the key mechanism causing the disease," says Ferguson-Smith. She says it is not yet clear what other mechanism might be at work.
She hypothesises that epigenetic inheritance is a short-term adaptation that allows the offspring to be programmed for a stressful environment, but one that can easily be erased if the stressor disappears. "It would make sense to have evolved mechanisms to sense short-term changes in the environment, such that when nutrition became normal again this adaptation wouldn't persist," says Ferguson-Smith.
The team is now investigating whether further generations have an increased risk of developing diabetes to shed some light on how many generations the impact of a parent's diet can last.
參考譯文：
一項(xiàng)小鼠實(shí)驗(yàn)表明，母親孕期營(yíng)養(yǎng)不足會(huì)增高子代和孫代發(fā)生肥胖及患上糖尿病的機(jī)會(huì)，但再下一代的健康將不再受影響。
如果這項(xiàng)結(jié)果對(duì)人類也適用的話，這就可能意味著我們生命中所遭遇的艱難困苦會(huì)影響我們孫輩的健康，但對(duì)我們的重孫輩沒有影響。
環(huán)境壓力能導(dǎo)致DNA發(fā)生化學(xué)變化，使得基因被打開或關(guān)閉。許多研究者相信，這些變化能通過精子或卵子遺傳到下一代——這種機(jī)制稱為“后成的遺傳”或“表觀遺傳”。
喂養(yǎng)
例如，已有研究表明二戰(zhàn)期間一些孕婦的營(yíng)養(yǎng)不良跟她們的孩子的一些基因變化有關(guān)，這些變化會(huì)提高肥胖發(fā)生與罹患癌癥的風(fēng)險(xiǎn)。然而，從她們的孫輩起會(huì)有什么變化，則不得而知。
為了建立研究該種影響的模型，劍橋大學(xué)的Anne Ferguson-Smith和她的同事對(duì)懷孕的小鼠進(jìn)行了喂養(yǎng)實(shí)驗(yàn)。在小鼠妊娠12天后至產(chǎn)仔這段時(shí)間內(nèi)（歷時(shí)約20天）以熱量比正常所需含量低一半的食物進(jìn)行喂養(yǎng)，結(jié)果子代小鼠的體型小于平均水平，并在正常的喂養(yǎng)條件下患上了糖尿病，而且其中的子代雄鼠的兒女們（即營(yíng)養(yǎng)不良雌鼠的孫輩）患糖尿病的風(fēng)險(xiǎn)也提高了。
該研究小組分析了營(yíng)養(yǎng)不良雌鼠的兒孫們的精子DNA，結(jié)果發(fā)現(xiàn)，與母親得到正常喂養(yǎng)的雄鼠的精子DNA相比，前者有111個(gè)區(qū)域發(fā)生了甲基化或去甲基化——一種常見的表觀遺傳學(xué)變化。
機(jī)制不明
然而，在正常喂養(yǎng)的條件下，上述變化（甲基化或去甲基化）從第四代小鼠的DNA中消失了。這一結(jié)果令人驚異，因?yàn)橹钡降谌∈�，它們�(nèi)允歉菀谆继悄虿〉�。Ferguson-Smith說，“這個(gè)結(jié)果暗示，甲基化只是一個(gè)標(biāo)志，但很可能并不是導(dǎo)致糖尿病的關(guān)鍵機(jī)理。”她還說，尚不明確是否另有其他致病機(jī)理。
她猜想，表觀遺傳是一種短期的適應(yīng)性，它使得小鼠后代得以應(yīng)對(duì)逆境，但一旦逆境壓力消失，這種適應(yīng)性也就隨之被清除。“合理的推斷是，它們進(jìn)化出了一些機(jī)制來感知短期的環(huán)境變化，因此當(dāng)小鼠的營(yíng)養(yǎng)供應(yīng)恢復(fù)正常后，這種適應(yīng)性也就不再持續(xù)。”
該研究小組將繼續(xù)研究更多代小鼠患糖尿病的風(fēng)險(xiǎn)是否會(huì)增高，以期探明母親的飲食對(duì)后代健康的影響到底能持續(xù)多少代。
原始來源：http://www.newscientist.com/article/dn25884-famine-puts-next-two-generations-at-risk-of-obesity.html#.VCUYUdyn8ZF
