個人經歷會對精子帶來改變嗎
In 2013, an obese man went to Hvidovre Hospital in Denmark to have his stomach stapled. All in all, it was ordinary bariatric surgery — with one big exception.
2013年，一名肥胖男子來到丹麥的哈維德夫醫院(Hvidovre Hospital)接受胃旁路手術。總的來說，這是一次普通的減肥手術——只有一點例外。
A week before the operation, the man provided a sperm sample to Danish scientists. A week after the procedure, he did so again. A year later, he donated a third sample.
手術前一週、術後一週以及術後一年，該男子分別向丹麥的科學家們提供了精子樣本。
Scientists were investigating a tantalizing but controversial hypothesis: that a man’s experiences can alter his sperm, and that those changes in turn may alter his children.
科學家們正在調查的是一個誘人但飽受爭議的假設：男性的經歷能夠改變他的精子，而這些變化反過來將會改變他的後代。
That idea runs counter to standard thinking about heredity: that parents pass down only genes to their children. People inherit genes that predispose them to obesity, or stress, or cancer — or they don’t. Whether one’s parents actually were obese or constantly anxious doesn’t rewrite those genes.
這與遺傳學“常識”背道而馳——過去人們一直認爲，父母只將基因遺傳給自己的孩子。人們繼承到的基因致使他們容易/或不易肥胖、緊張或是患癌症。無論這個人的父母實際上是否肥胖或經常焦慮都不會改寫這些基因。
Yet a number of animal experiments in recent years have challenged conventional thinking on heredity, suggesting that something more is at work.
然而，近年來的大量動物實驗表明，還有一些其他的東西參與了遺傳，這對上述傳統觀念提出了挑戰。
In 2010, for example, Dr. Romain Barres of the University of Copenhagen and his colleagues fed male rats a high-fat diet and then mated them with females. Compared with male rats fed a regular diet, those on the high-fat diet fathered offspring that tended to gain more weight, develop more fat and have more trouble regulating insulin levels.
例如，2010年，哥本哈根大學的羅邁因·巴雷斯(Romain Barres)博士和他的同事們以高脂肪飲食飼餵雄性大鼠，然後讓其與雌性交配。與飼餵正常飲食的雄性大鼠相比，飼餵高脂肪飲食的大鼠的後代往往更容易增重，更容易合成脂肪，在調節胰島素水平方面也存在更多的問題。
Eating high-fat food is just one of several experiences a father can have that can change his offspring. Stress is another. Male rats exposed to stressful experiences — like smelling the odor of a fox — will father pups that have a dampened response to stress.
食用高脂肪食物只是一個例子，除此之外，還有一些父親的經歷會給後代帶來改變，譬如，壓力。暴露於應激環境（比如聞到狐狸的氣味等）的雄性大鼠的後代對壓力的反應有所降低。
To find the link between a father’s experiences and his offspring’s biology, scientists have taken a close look at sperm. A sperm cell delivers DNA to an egg, of course. But those genes are regulated by swarms of molecules, so-called epigenetic factors.
爲了尋找父親的經歷與其後代的生物學性狀之間的聯繫，科學家們仔細研究了父親們的精子。我們都知道，精子將父親的DNA帶進了卵細胞。但這些基因會受到衆多的分子，即所謂的表觀遺傳學因素的調節。
These molecules can respond to environmental influences by silencing some genes and activating others as needed. Some studies suggest the changes in epigenetic factors can be handed down to offspring via sperm.
這些分子可對環境的影響作出應答，根據需要令一些基因沉默，並激活其他基因。一些研究表明，表觀遺傳因素的變化可以通過精子傳給後代。
When Dr. Tracy L. Bale, a neuroscientist at the University of Pennsylvania, and her colleagues looked at the sperm of stressed male rats, for example, they found unusual levels of epigenetic molecules called microRNAs.
例如，賓夕法尼亞大學(University of Pennsylvania)的神經科學家特蕾西·L·貝爾(Tracy L. Bale)博士和她的同事們在觀察了應激狀態下的雄性大鼠的精子後，發現名爲microRNA（微小RNA）的表觀遺傳學分子水平異常。
They created a cocktail of microRNAs and injected them into embryos from mellow fathers. As Dr. Bale and her colleagues reported recently, the embryos developed into rats with altered stress responses.
他們製造了這些microRNA的混合物，並將其注射入成熟雄鼠授精產生的胚胎中。貝爾博士和她的同事們最近報告稱，這些胚胎髮育而來的大鼠的應激反應也發生了改變。
The notion that environmental responses might influence human health in similar ways has huge implications. But scientists have only started to investigate the epigenetics of fatherhood. As is often the case when scientists turn from animal experiments to humans, the results have been provocative but hardly clear-cut.
環境很可能也是在以類似的方式影響人類的健康，這個概念的提出具有深遠的意義。不過，科學家們對父親表觀遺傳學因素的調查纔剛剛起步。當實驗從動物轉向人類，常常能獲得令人振奮的結果，卻幾乎都不明確。
In 2013, Adelheid Soubry, a molecular epidemiologist at KU Leuven University in Belgium, and her colleagues studied 79 newborn children. They found epigenetic differences between children with obese fathers and those with lean ones.
2013年，比利時荷語天主教魯汶大學(KU Leuven University)的分子流行病學家阿德爾海德·蘇布賴(Adelheid Soubry)和她的同事們研究了79名新生兒。他們發現，肥胖父親與精瘦父親的後代之間存在着表觀遺傳學差異。
Are changes like these actually caused by men’s obesity? Dr. Barres and his colleagues set out to investigate that potential link in two ways.
但這些變化確實是由他們父親的肥胖引起的麼？巴雷斯博士和同事們以兩種方式調查了其間的潛在關聯。
First, they collected sperm from 10 obese Danish men and 13 lean ones. They found numerous epigenetic differences. One type of epigenetic factor they looked at involved molecular caps that are placed on DNA in a process called methylation. Dr. Barres and his colleagues found more than 9,000 genes in which the methylation pattern differed between lean and obese men.
首先，他們收集了10名肥胖的丹麥男性和13名精瘦的丹麥男性的精子，發現其間存在很多表觀遺傳學差異。其中一種表觀遺傳學因素涉及甲基化過程中被加在DNA上的“分子帽子”。巴雷斯博士和同事們發現，精瘦男性與肥胖男性間有9000多個基因的甲基化模式都有所不同。
Then the scientists recruited six obese men getting bariatric surgery to see how losing weight changed these methylation patterns. In a report published on Thursday in the journal Cell Metabolism, Dr. Barres and his colleagues identified more than 3,900 genes that were methylated differently a year after surgery.
其後，科學家們招募了六名將要接受減肥手術的肥胖男子，以調查減肥會給這些甲基化模式帶來怎樣的改變。在12月3日發表在《細胞-代謝》(Cell Metabolism)雜誌上的文章中，巴雷斯博士及其同事報告，他們發現在手術後一年，有3900多個基因的甲基化發生了變化。
Among the genes that are epigenetically altered are those that affect such behaviors as appetite control. But the new study does not show whether those changes have any effect on a father’s children, Dr. Barres said.
在這些發生了表觀遺傳學改變的基因中，有一些可以影響食慾控制等行爲。不過，該研究並沒有顯示這些變化是否會影響他們的孩子，巴雷斯博士說。
“I don’t want to speculate whether it’s positive or negative in the following generation,” he said.
“我不想去妄加揣測這對下一代會有正面還是負面的作用。”他說。
Dr. Barres and his colleagues are now expanding on the study by comparing epigenetic patterns in the sperm of obese fathers with the patterns in the blood cells of their offspring. “We’re going to try to see if there’s something transmitted all the way down,” Dr. Barres said.
巴雷斯博士和同事們現在正進一步深化研究，對肥胖父親與其後代的血細胞中的表觀遺傳學模式進行比較。巴雷斯博士說：“我們想要看看有沒有什麼東西遺傳了下來。”
Other scientists had mixed views about the study. On one hand, they agreed that the researchers used sophisticated methods to survey epigenetic differences in the sperm. But they were wary of drawing broad conclusions.
其他科學家對該研究的看法不一。一方面，他們都認同研究人員採用了周密的方法來調查精子中的表觀遺傳學差異。但另一方面，他們也表示應慎下結論。
Dr. John M. Greally, an epigenetics expert at the Albert Einstein College of Medicine, said it was possible that genetic differences between the men were mostly to blame for the differences seen in their sperm.
阿爾伯特·愛因斯坦醫學院(Albert Einstein College of Medicine)的表觀遺傳學專家約翰·M·格里曆(John M. Greally)博士說，在這些男子的精子中發現的差異可能是他們之間的遺傳差異造成的。
He also shared a concern with Dr. Bale and Dr. Soubry that the study involved too few men. The differences in such a small sample might have occurred randomly.
此外，他與貝爾博士以及蘇布賴博士都認爲，該研究的被試過少。這麼小的樣本量，差異可能是隨機產生的。
“Honestly, I think a lot of what they have is noise,” Dr. Greally said.
“說實話，我覺得其中很多都是噪音，”格里曆博士說。
That doesn’t mean that Dr. Greally thinks the Danish scientists are wrong, but rather that pinning down the epigenetic effects that fathers pass to their children will take much more work.
但這並不代表格里曆博士認爲丹麥科學家們的觀點是錯誤的，他只是認爲，要證實父親遺傳給孩子們的這些表觀遺傳學效應，還需要進行更多的工作。
“I’d say, let’s do a study of hundreds of people,” Dr. Greally said. “It’s doable. It just requires that we’re bold about doing these things.”
“我想說，讓我們來做一個納入幾百名被試的研究吧，”格里曆博士說。“這應該是可行的，只要我們大膽去做就好。”
