《經濟學人》5月26日卷文章：「緊張的人格如何代代相傳」

06-03

（How stress echoes down the generations https://www.economist.com/science-and-technology/2018/05/26/how-stress-echoes-down-the-generations?frsc=dg%7Ce）全文譯述，英文附後：

導語：童年創傷的影響可能通過精子傳遞

兒童遭受虐待可能影響他一生。被忽視或被虐待的兒童成年後罹患各種疾病的風險增高，不僅包括抑鬱症等精神疾病，也包括癌症和中風等器質性病變。事實上，這種影響可能會持續更長時間。新出現的證據表明，兒童遭受虐待的後果可能會延續，影響受害者的子孫，即使子孫自己沒有受過虐待。

這種情況究竟是如何發生的並不很好理解。對人體進行嚴格的實驗是困難的，科學家們因此轉向小白鼠和老鼠。但現在塔夫茨大學的拉里·菲格（ Larry

Feig）和他的同事們已經揭示，心理壓力似乎導致了老鼠和男人的精子發生類似的變化。他們的研究本周在《轉化精神病學》（Translational Psychiatry）上發表。

生物學家知道，性狀是由基因世代傳承下來的。基因編碼蛋白質，蛋白質組成生物體。這仍然是事實，但還不是整個故事。這一點最近變得清楚了。有機體在整個生命過程中調節其基因的活性，根據環境需要開關不同的基因。這種「表觀遺傳」（「epigenetic」）現象可能與基因本身一起傳遞給後代。表觀遺傳現象提供了一種機制，通過這種機制動物的生活經歷可以對後代產生影響制。

為了尋找這種跡象，費格博士和同事們要求28名男性志願者完成一份問卷，評估他們小時候所遭受的任何精神創傷的嚴重程度。他們還要求志願者提供精子樣本。然後研究人員在其中尋找共同的、存在表觀遺傳機制的證據，這個機制涉及稱為「micro-RNAs」的小分子。這些小分子的作用是綁定於另一個稱為「信使RNA」的分子，後者的任務是將從基因中讀取的信息傳送到創建所需蛋白質的細胞工廠。

Micro-RNA使信使RNA失活，降低了有關基因的活性，而且它通過精子與DNA一起傳遞。

果然，在篩查男性精子後，研究人員發現在童年受到虐待的男性的樣本中，兩類miro-RNA（miR-34和miR-449）的濃度低了100倍。

研究人員然後轉向受試的老鼠。對老鼠施壓的一個標準方法是將幼鼠一次又一次轉移到新的籠子里，與新的同伴為伍，直到它們成年。當研究小組這樣做時，他們發現在經受壓力的這些老鼠的精子中，miR-34和miR-449的水平較低。他們讓這些雄鼠與未經受壓力的雌鼠交配，所生出的胚胎，兩類miro-RNA水平也較低。而且，這樣交配生下的雄性後代，其精子中的兩類miro-RNA水平同樣很低。

費格博士和其他人員的研究表明，遭受壓力的雄鼠的雌性後代傾向於有焦慮感，不善於交際。此外，遭受壓力而情緒緊張的父親的兒子也會生出情緒緊張的女兒。換句話說，換籠飼養的效果似乎至少持續三代。研究人員尚未明確證實miR-34和miR-449是這種遺傳的主因，但他們的研究結果具有啟發性。

為了做實因果關係，研究人員計划進行更大規模的研究。這一次，他們會對他們的人類受試者的父親進行問卷調查，以了解觀察到的任何錶觀遺傳變化是源於受試者自己還是他父親的童年經歷。受試者的姐妹和女兒也可能被納入研究。這是一個雄心勃勃但很有價值的目標。涉及基因的遺傳變化是固定不變的，除非有朝一日基因工程得以完善、從而能夠找到解決辦法。但是，表觀遺傳效應有可能是可以治療的，例如通過提高精子中特定miro-RNA的水平。這意味著，虐童的後果將不再傳給子孫後代。

Science and technology

Genetics

How stress echoes down the generationsThe effects of childhood trauma may be passed on through sperm

THE effects of child abuse can last a lifetime. Neglected or abused children have a

higher risk of developing all sorts of ailments as adults, including mental

illnesses such as depression but also physical ones like cancer and stroke. In

fact, the effects may last even longer. Emerging evidence suggests that the

consequences of mistreatment in childhood may persist down the generations,

affecting a victim』s children or grand-children, even if they have experienced

no abuse themselves.

Exactly how this happens is not well understood. Rigorous experiments on human subjects are difficult. Scientists have therefore turned to rats and mice. But now Larry

Feig of Tufts University and his colleagues have shown that psychological stress

seems to cause similar changes in the sperm of both mice and men. Their study

is published this week in Translational Psychiatry.

Biologists know that traits are carried down the generations by genes. Genes encode

proteins, and proteins make up organisms. That is still true. But it has

recently become clear that it is not the whole story. Organisms regulate the

activity of their genes throughout their lives, switching different genes on

and off as circumstances require. It is possible that such 「epigenetic」

phenomena can be passed, along with the genes themselves, to an animal』s

descendants. They offer a mechanism by which an animal』s life experiences can

have effects on its offspring.

Hunting for signs of this, Dr Feig and his colleagues asked 28 male volunteers to

complete a questionnaire assessing the severity of any trauma they had

experienced as youngsters. They also asked their volunteers to provide sperm

samples. They then looked for evidence for a common epigenetic mechanism

involving small molecules called micro-RNAs. Their job is to bind to another

molecule called messenger RNA, whose task in turn is to ferry information read

from a gene to the cellular factories that create the required protein.

Micro-RNA renders messenger RNA inactive, reducing the activity of the gene in

question—and it can travel in sperm alongside DNA.

Sure enough, upon screening the men』s sperm, the researchers found that

concentrations of two types of micro-RNAs, miR-34 and miR-449, were as much as

100 times lower in samples from abused men.

The team then turned to their mice. A standard way to stress mice is to move them

to new cages, with new mice, from time to time until they reach adulthood. When

the team did this they found that the stressed males had lower levels of miR-34

and miR-449 in their sperm. They mated these males with unstressed females. The

resulting embryos also had low levels of the two micro-RNAs. And so in turn did

sperm produced by the male offspring of these unions.

Dr Feig and others have shown that the female offspring of stressed male mice tend

to be more anxious and less sociable. Furthermore, the sons of stressed fathers

themselves produce stressed daughters. The effects of cage-shuffling, in other

words, seem to last for at least three generations. The researchers have not

demonstrated conclusively that miR-34 and miR-449 are responsible. But their

results are suggestive.

To try to nail their case, the researchers plan to carry out a bigger study. This

time, they will give questionnaires to their human subjects』 fathers, to tease

out whether any epigenetic changes they observe arise from the childhood

experiences of the subject or his father. Sisters and daughters may be included

in the study, too. That is an ambitious goal. It is also a worthy one. Unless

genetic engineering can one day be perfected, changes in genes are hard-wired.

But epigenetic effects might be treatable, by boosting levels of particular

micro-RNAs in sperm, for example. That could mean the legacy of abuse is no

longer passed to future generations.