Do you take after your dad’s RNA?
Do you take after your dad’s RNA?
你是否遗传了父亲的 RNA？
On a bright afternoon in Jiangsu, China, Xin Yin is playing personal trainer to some mice. One by one, he sets the rodents on a miniature treadmill that starts slow and gradually speeds up. These littermates are born athletes, able to run farther with less lactic acid buildup than average laboratory mice. The secret to their speediness isn’t carried in their genes—the animals come from the same genetic stock as a group of control mice. And they haven’t received any special training. Instead, their fitness seems to stem from their father’s exercise habits before they were even conceived. It’s a finding suggesting that running might benefit not just the exerciser, but also his unborn children.
在中国江苏一个明媚的午后，殷鑫（音译）正在为几只小鼠担任私人教练。他将这些啮齿动物一只接一只地放在一台微型跑步机上，跑步机从慢速开始，逐渐加速。这些同窝出生的小鼠是天生的运动员，与普通的实验室小鼠相比，它们能跑得更远，且乳酸堆积更少。它们速度快的秘诀并不在于基因——这些动物与对照组小鼠来自相同的遗传种群，而且它们也没有接受过任何特殊训练。相反，它们的体能似乎源于它们父亲在受孕前的运动习惯。这一发现表明，跑步不仅能让锻炼者本人受益，还可能惠及他尚未出生的后代。
“I was very surprised when I first saw the data,” says Yin, a biochemist at Nanjing University. Yin’s team analyzed the molecules inside the exercising rodents’ sperm and found tiny bits of RNA—dubbed microRNAs—that were present in higher amounts than in the sperm of their idle littermates. When the scientists injected those molecules into unrelated embryos, they got animals just as fit as those that were born to exercising fathers. That 2025 study adds to mounting evidence that sperm are more than wriggling vessels carrying DNA to an egg.
“当我第一次看到这些数据时，我感到非常惊讶，”南京大学的生物化学家殷鑫说。殷鑫的团队分析了运动小鼠精子内的分子，发现其中含有微量的 RNA（被称为 microRNA），其含量高于那些不运动的同窝小鼠的精子。当科学家将这些分子注射到无关的胚胎中时，他们培育出的动物与那些父亲经常运动的小鼠一样健康。这项 2025 年的研究进一步证明，精子不仅仅是携带 DNA 到达卵子的游动容器。
Over the past two decades, studies in mice have detected microRNAs and other types of RNA fragments that surge and wane inside sperm cells in response to not just exercise or sloth but also fatty or sugary diets, daily stress, childhood trauma, heavy drinking and exposure to pesticides and other hazards. In step with these changes, researchers have documented developmental and metabolic changes and differing rates of depression in the males’ offspring. And while it’s difficult to study the effect in people, researchers also have documented fluctuations in RNA fragments in the sperm of men who do or don’t exercise, smoke or eat excess sugar, as well as men with obesity or traumatic childhoods. Studies also report that children of parents who are overweight or who dealt with mental health stress are more likely to have those conditions, too.
在过去的二十年里，针对小鼠的研究发现，精子细胞内的 microRNA 和其他类型的 RNA 片段会随着环境因素的波动而增减，这些因素不仅包括运动或懒惰，还包括高脂肪或高糖饮食、日常压力、童年创伤、酗酒以及接触杀虫剂和其他有害物质。随着这些变化，研究人员记录了雄性后代在发育、代谢方面的改变以及抑郁症发病率的差异。虽然在人类身上研究这种影响很困难，但研究人员也记录了男性精子中 RNA 片段的波动，这些男性有的运动，有的不运动，有的吸烟或摄入过量糖分，还有的患有肥胖症或有童年创伤经历。研究还报告称，父母超重或承受心理健康压力，其子女也更有可能出现这些状况。
Until recently, however, most evidence linking small sperm RNAs to environmental challenges and subsequent effects in offspring has been correlational. Attempts to pin down causality—by injecting RNAs directly into embryos—have often used far higher RNA concentrations than typically found in sperm. In fact, there was no proof that the RNA fragments even make it inside the egg. But though puzzles remain, recent studies show that not only are paternal RNA fragments transferred to a fertilized egg, but also that they are capable of inducing changes in the offspring at the doses found in sperm.
然而直到最近，大多数将精子小 RNA 与环境挑战及后代后续影响联系起来的证据仍处于相关性阶段。试图确定因果关系的尝试——通过将 RNA 直接注射到胚胎中——往往使用了远高于精子中通常含量的 RNA 浓度。事实上，此前并没有证据表明这些 RNA 片段确实能进入卵子。但尽管谜团依然存在，最近的研究表明，父系 RNA 片段不仅能传递到受精卵中，而且在精子中发现的剂量下，它们确实能够诱导后代发生变化。
Epigenetic effects
表观遗传效应
Researchers first noticed the intergenerational effects of paternal lifestyle back in the 1960s, but it was decades before they started experimental investigations using animal models. Today, those studying the phenomenon are sure the effects exist but aren’t certain how they are transmitted. The end result, they believe, is adjustments to the activity of genes—a phenomenon known as epigenetics. Such adjustments occur during normal development as tissues and organs adopt their different identities, which require certain genes to be active or to be turned off. Epigenetic changes also occur throughout our lives, due to factors including exposures to certain chemicals, and activities such as smoking—and, maybe, exercise, stress, fatty diets, and more. Such changes can occur in myriad body cells, including those that give rise to sperm.
研究人员早在 20 世纪 60 年代就注意到了父亲生活方式的代际影响，但直到几十年后，他们才开始使用动物模型进行实验研究。今天，研究这一现象的人确信这种影响是存在的，但尚不确定它是如何传递的。他们认为，最终结果是对基因活性的调节——这一现象被称为表观遗传学。这种调节发生在正常的发育过程中，随着组织和器官获得其不同的身份，需要某些基因处于活跃状态或被关闭。表观遗传变化也发生在我们的一生中，原因包括接触某些化学物质，以及吸烟等活动——或许还有运动、压力、高脂肪饮食等。这种变化可以发生在无数的身体细胞中，包括那些产生精子的细胞。
As evidence mounted that sperm somehow transmit environmental information to a male’s children, researchers started probing the epigenetic mechanisms that might be responsible. Several possibilities exist: methyl groups that turn down gene activity when they accumulate on genes, and acetyl groups that attach to the protein spools called histones, around which the DNA wraps. These tend to ramp up activity of nearby genes. But methyl groups aren’t easily passed to the next generation: Fertilized eggs erase most of these marks from both sets of chromosomes before the embryo starts to divide. And mature sperm replaces most histones with its own proteins, limiting transmission of information this way.
随着越来越多的证据表明精子以某种方式将环境信息传递给男性的子女，研究人员开始探索可能负责的表观遗传机制。存在几种可能性：当甲基在基因上积累时会降低基因活性；乙酰基则会附着在被称为组蛋白的蛋白质线轴上（DNA 缠绕在组蛋白周围），这往往会增强附近基因的活性。但甲基不容易传递给下一代：在胚胎开始分裂之前，受精卵会抹去两组染色体上的大部分此类标记。而且成熟的精子会用自身的蛋白质取代大部分组蛋白，从而限制了通过这种方式传递信息。
Today, the idea that small RNAs carry environmental signals has the most direct evidence behind it. Although small RNAs are short-lived, they aren’t actively removed like other epigenetic marks. Somehow, the tiny bits of nucleic acid fluctuate in response to the environment, then find their way into sperm cells. At first, researchers hypothesized that sperm manufacture these microscopic molecules in the testes, where stem cells morph into fledgling spermatozoa that are not yet fertile or able to swim. The problem, though, is that as they develop, sperm whittle down their insides to little more than the nucleus containing the male chromosomes and the mitochondria, cellular powerhouses that fuel the sperm’s odyssey to the egg.
如今，小 RNA 携带环境信号的观点拥有最直接的证据支持。虽然小 RNA 的寿命很短，但它们不像其他表观遗传标记那样会被主动清除。这些微小的核酸片段以某种方式响应环境而波动，然后进入精子细胞。起初，研究人员假设精子是在睾丸中制造这些微小分子的，在那里干细胞转化为尚未具有受精能力或游动能力的幼年精子。然而问题在于，随着精子的发育，它们会精简内部结构，最终几乎只剩下包含雄性染色体的细胞核和线粒体——即为精子前往卵子的漫长旅程提供动力的细胞“发电厂”。
New clues emerged in 2016, when Colin Conine and Upasna Sharma, postdocs in the lab of epigeneticist Oliver Rando at the University of Massachusetts’ Chan Medical School, and colleagues, cataloged the molecular makeup of sperm from male mice exposed to low protein diets. Sperm extracted from the testes and the epididymis—a convoluted tube that carries the sperm out of the testes—contain different RNA payloads. And small bubbles found in the walls of the epididymis—called epididymosomes—were found to carry a cargo of RNA fragments matching those found in mature sperm. The team later confirmed their hunch: Sperm take up small RNAs from epididymosomes during their cruise through the winding tube, stockpiling environmental information. Other groups later reported that movement through the epididymis was associated with a reconfiguration of small RNA.
2016 年出现了新的线索，当时马萨诸塞大学陈医学院表观遗传学家奥利弗·兰多（Oliver Rando）实验室的博士后科林·科宁（Colin Conine）和乌帕斯娜·夏尔马（Upasna Sharma）及其同事，对暴露于低蛋白饮食的雄性小鼠的精子分子组成进行了编目。从睾丸和附睾（将精子运出睾丸的盘曲管道）中提取的精子含有不同的 RNA 载荷。研究人员在附睾壁中发现的小气泡——称为附睾体（epididymosomes）——被发现携带了一批与成熟精子中发现的相匹配的 RNA 片段。该团队后来证实了他们的猜想：精子在穿过这条蜿蜒管道的过程中，会从附睾体中摄取小 RNA，从而储存环境信息。其他研究小组后来也报告称，精子在附睾中的运动与小 RNA 的重构有关。