How Dad’s Fitness May Be Packaged and Passed Down in Sperm RNA

A father’s fitness, as measured by diet and exercise, is encoded by sperm RNA and epigenetically affects his offspring, according to research in mice.

根据小鼠研究，父亲的健康状况（通过饮食和锻炼来衡量）由精子 RNA 编码，并通过表观遗传影响他的后代。

The standard sperm-meets-egg story posits that sperm cells are hardly more than bundles of shrink-wrapped DNA with tails.

标准的精子与卵子相遇的故事认为，精子细胞只不过是一束带尾巴的收缩包装的 DNA。

Their mission is simple: Deliver a father’s genes into a mother’s egg for sexual reproduction.

他们的使命很简单：将父亲的基因传递到母亲的卵子中进行有性繁殖。

Just about all other aspects of a developing embryo, including its cellular and environmental components, have nothing to do with dad.

发育中的胚胎的几乎所有其他方面，包括其细胞和环境成分，都与父亲无关。

Those all come from mom.

这些都是妈妈给的。

But nearly two decades of studies from multiple independent labs threaten to rewrite that story.

但多个独立实验室近二十年的研究有可能改写这个故事。

They suggest that dad’s gametes shuttle more than DNA: Within a sperm’s minuscule head are stowaway molecules, which enter the egg and convey information about the father’s fitness, such as diet, exercise habits and stress levels, to his offspring.

他们认为，父亲的配子比 DNA 更重要：在精子的微小头部内有偷渡分子，它们进入卵子并向后代传达有关父亲健康状况的信息，例如饮食、运动习惯和压力水平。

These non-DNA transfers may influence genomic activity that boots up during and after fertilization, exerting some control over the embryo’s development and influencing the adult they will become.

这些非 DNA 转移可能会影响受精期间和受精后启动的基因组活性，对胚胎的发育施加一定的控制并影响它们将成为的成年人。

Growing evidence in mouse models suggests that non-DNA sperm molecules can pass along a dad’s condition at the time of conception.

越来越多的小鼠模型证据表明，非 DNA 精子分子可以在受孕时遗传父亲的状况。

The findings, so far largely described in mouse models, could end up changing the way we think about heredity.

迄今为止，这些发现主要是在小鼠模型中描述的，最终可能会改变我们对遗传的看法。

They suggest “that what we do in this life affects the next generation,” said Qi Chen , a reproductive and developmental biologist at the University of Utah Medical School who is among the pioneers of this research.

他们认为，“我们今生所做的事情会影响下一代，”这项研究的先驱之一、犹他大学医学院的生殖与发育生物学家 Qi Chen 说。

In other words: What a father eats, drinks, inhales, is stressed by or otherwise experiences in the weeks and months before he conceives a child might be encoded in molecules, packaged into his sperm cells and transmitted to his future kid.

换句话说：父亲在怀孕前几周或几个月所吃的、喝的、吸入的、承受的压力或其他经历可能会被编码成分子，包装到他的精子细胞中并传递给他未来的孩子。

The researchers have largely zeroed in on RNA molecules, those short-lived copies of DNA that reflect genetic activity at a given time.

研究人员主要关注 RNA 分子，即反映特定时间遗传活动的短暂 DNA 副本。

It’s a tantalizing notion.

这是一个诱人的想法。

But the mechanistic details — how experience is encoded, how it’s transferred from sperm to egg, and whether and how it affects a developing embryo — are not easy to unpack, especially given the challenges of conducting research in human subjects.

但机制细节——经验如何编码、经验如何从精子转移到卵子，以及它是否以及如何影响发育中的胚胎——并不容易解开，特别是考虑到在人类受试者中进行研究的挑战。

For this reason, and because of the potentially textbook-rewriting implications of the findings, researchers, including those spearheading the work, are cautious about overselling their results.

出于这个原因，并且由于这些发现可能会重写教科书，研究人员，包括那些带头开展这项工作的人，对过度吹嘘他们的结果持谨慎态度。

Colin Conine has shown that RNAs packaged in sperm alter gene expression in mouse embryos, pointing to a pathway by which a dad’s choices can epigenetically affect his offspring.

Colin Conine 证明，精子中包装的 RNA 会改变小鼠胚胎中的基因表达，这表明父亲的选择可以通过表观遗传影响他的后代。

“It’s still very hand-wavy,” said the epigeneticist Colin Conine of the University of Pennsylvania Perelman School of Medicine and Children’s Hospital of Philadelphia, who has been trying to uncover the mechanics of how sperm RNA can contribute nongenetic information to progeny.

宾夕法尼亚大学佩雷​​尔曼医学院和费城儿童医院的表观遗传学家科林·科宁 (Colin Conine) 表示：“这仍然非常困难。”他一直试图揭示精子 RNA 如何向后代提供非遗传信息的机制。

Some elements of the story are clear, he said: Researchers have significant evidence that the environment can regulate sperm RNAs, that these molecules transmit traits to offspring and that they can regulate embryonic development after fertilization.

他说，这个故事的一些要素很清楚：研究人员有重要证据表明环境可以调节精子 RNA，这些分子将性状传递给后代，并且它们可以调节受精后的胚胎发育。

“We just don’t have really any understanding of how RNAs can do this, and that’s the hand-wavy part,” Conine said.

“我们只是不知道 RNA 是如何做到这一点的，这就是挥手的部分，”Conine 说。

But evidence keeps piling up.

但证据不断堆积。

Most recently, in November 2025, a comprehensive paper published in Cell Metabolism traced the downstream molecular effects of a father mouse’s exercise regimen on sperm microRNAs that target genes “critical for mitochondrial function and metabolic control” in a developing embryo.

最近，2025 年 11 月，《细胞代谢》上发表的一篇综合论文追踪了父亲小鼠的运动方案对精子 microRNA 的下游分子影响，这些 microRNA 的目标基因是发育中胚胎中“对线粒体功能和代谢控制至关重要”的基因。

The researchers found many of those same RNAs overexpressed in the sperm of well-exercised human men.

研究人员发现，在锻炼良好的人类男性的精子中，许多相同的 RNA 过度表达。

“This study shows that paternal exercise can confer benefits — enhanced endurance and metabolic health — to offspring,” said Chen, who was not involved in the study.

“这项研究表明，父亲的锻炼可以给后代带来好处——增强耐力和代谢健康，”未参与这项研究的陈说。

“It’s a powerful reminder that many sperm-mediated epigenetic effects are deeply adaptive in nature.”

“这有力地提醒我们，许多精子介导的表观遗传效应本质上具有很强的适应性。”

The possibility that a previously undocumented avenue of inheritance is at play is too important to ignore.

以前未记录的继承途径发挥作用的可能性非常重要，不容忽视。

That’s why the researchers are now hunkering down in their labs to trace out the molecular processes that would have to operate for a father’s here-and-now experience to be transferred as developmental instructions to his partner’s egg.

这就是为什么研究人员现在蹲在实验室里，追踪父亲此时此地的经历必须作为发育指令转移到其伴侣的卵子上的分子过程。

In most animals, a sperm cell is tiny compared to an egg cell.

在大多数动物中，精子细胞与卵细胞相比很小。

In humans, an egg contains 10 million times the volume of a sperm and contributes most cellular components — nutrition, cytoplasm, mitochondria and other organelles, the molecular machinery to make proteins, and more — to a zygote (a newly fertilized egg that hasn’t started dividing).

在人类中，卵子的体积是精子的 1000 万倍，并为受精卵（尚未开始分裂的新受精卵）提供大部分细胞成分（营养、细胞质、线粒体和其他细胞器、制造蛋白质的分子机制等）。

Plus, a mother provides the environment within which an embryo and then fetus develops and grows.

另外，母亲还提供胚胎和胎儿发育和生长的环境。

As a result, the effect of a mother’s health on her children has long been scrutinized , including at the molecular level .

因此，母亲健康对孩子的影响长期以来一直受到人们的关注，包括在分子水平上。

But over the past 15 years or so, the evidence for some kind of non-DNA inheritance of paternal experience has also been strengthening.

但在过去 15 年左右的时间里，关于父亲经历的某种非 DNA 遗传的证据也在不断加强。

“There are many different labs that have done diet and stress studies, and typically the readouts of those in the next generation are either metabolism or behavioral changes,” Conine said.

“有许多不同的实验室进行了饮食和压力研究，通常下一代的读数要么是新陈代谢，要么是行为变化，”科宁说。

Feed a male mouse a high-fat or low-protein diet, or take him away from his mom when he is young, and his offspring will inherit traits, such as changes in mitochondrial function, related to those environmental conditions.

给雄性小鼠喂食高脂肪或低蛋白质饮食，或者在它年轻时将其从母亲身边带走，它的后代将继承与这些环境条件相关的特征，例如线粒体功能的变化。

These traits aren’t necessarily detrimental.

这些特征不一定是有害的。

For instance, mouse fathers exposed to nicotine sire male pups with livers that are good at disarming not just nicotine but cocaine and other toxins as well.

例如，暴露于尼古丁的老鼠父亲，其肝脏的雄性幼崽不仅擅长解除尼古丁，还擅长解除可卡因和其他毒素。

There is a survival logic here, said Oliver Rando , an epigeneticist at the University of Massachusetts Chan Medical School who led the nicotine study.

领导尼古丁研究的马萨诸塞大学陈医学院表观遗传学家奥利弗·兰多（Oliver Rando）说，这里有一个生存逻辑。

It’s reasonable to expect that offspring will experience an environmental context similar to that of their parents.

可以合理地预期后代将经历与父母相似的环境背景。

Biologically priming them for those conditions could therefore help them survive.

因此，从生物学角度引导它们适应这些条件可以帮助它们生存。

The epigeneticist Oliver Rando suspects that sperm RNAs control early gene regulation in an embryo.

表观遗传学家 Oliver Rando 怀疑精子 RNA 控制着胚胎的早期基因调控。

If he’s right, he will have helped discover a new fact of life, he said.

他说，如果他是对的，他将帮助发现生活的新事实。

“You might think of this as a way to tell your kids something useful for them so that they can be better at dealing with the world they inherit,” said Rando, a father of two boys.

“你可能会认为这是告诉你的孩子一些对他们有用的东西的一种方式，这样他们就能更好地应对他们继承的世界，”两个男孩的父亲兰多说。

But logic does not make the story true.

但逻辑并不能证明这个故事是真的。

That’s why Chen, Rando, Conine and other researchers have been working to uncover the mechanistic components of dad-based epigenetic heredity to add to what is already known about these processes in mothers.

这就是为什么 Chen、Rando、Conine 和其他研究人员一直致力于揭示基于父亲的表观遗传遗传的机制组成部分，以补充对母亲这些过程的已知了解。

“Epigenetics” refers to heredity processes that do not change the DNA sequences of genes, but rather involve when and to what degree genes are expressed and made into functional proteins.

“表观遗传学”是指不改变基因DNA序列的遗传过程，而是涉及基因表达并形成功能蛋白的时间和程度。

Epigeneticists focus on the molecular biology that unfolds around genomic and chromosomal frameworks that can switch genes on and off in response to internal and external cues.

表观遗传学家专注于围绕基因组和染色体框架展开的分子生物学，这些框架可以根据内部和外部线索打开和关闭基因。

You might think of this as a way to tell your kids something useful for them so that they can be better at dealing with the world they inherit.

您可能会认为这是告诉您的孩子一些对他们有用的东西的一种方式，以便他们能够更好地应对他们继承的世界。

Oliver Rando, University of Massachusetts Chan Medical School

Oliver Rando，马萨诸塞大学陈医学院

This kind of differential gene expression is central to some of biology’s greatest wonders — for example, the fact that all cells in the human body have the same DNA, and yet brain cells differ dramatically from liver, skin and blood cells.

这种差异性基因表达是一些生物学最伟大奇迹的核心——例如，人体内的所有细胞都具有相同的 DNA，但脑细胞与肝脏、皮肤和血细胞却截然不同。

Some cues that trigger changes in gene expression are programmed into DNA, while others come from the environment — for example, a dearth of calories or nutrients due to food deprivation, or rising cortisol levels due to stressors such as the absence of parental care.

一些触发基因表达变化的线索被编入DNA，而另一些则来自环境——例如，由于食物匮乏而导致热量或营养物质的缺乏，或者由于缺乏父母照顾等压力因素而导致皮质醇水平升高。

These conditions affect the kinds of metabolites and other molecules circulating in our bodies, which influences what kinds of reactions and genomic processes cells can carry out.

这些条件会影响我们体内循环的代谢物和其他分子的种类，从而影响细胞可以进行的反应和基因组过程的种类。

Some molecules involved in epigenetic processes, such as methyl or acetyl groups, interface directly with DNA or bind to proteins attached to DNA.

一些参与表观遗传过程的分子，例如甲基或乙酰基，直接与 DNA 相互作用或与 DNA 上附着的蛋白质结合。

These actions loosen up or batten down portions of the genome and are akin to opening or closing doors to specific genes.

这些行为会放松或抑制基因组的某些部分，类似于打开或关闭特定基因的大门。

RNA molecules — flexible, ephemeral versions of DNA sequences — can also intervene in gene expression.

RNA 分子——DNA 序列的灵活、短暂的版本——也可以干预基因表达。

But because they are relatively short-lived, sometimes surviving mere minutes or hours before degrading, they have been overlooked as epigenetic regulators.

但由于它们的寿命相对较短，有时在降解前仅存活几分钟或几小时，因此它们作为表观遗传调节剂而被忽视。

Since the 1990s, their roles have been clarified, as has their longevity: Certain RNAs can survive for weeks or longer.

自 20 世纪 90 年代以来，它们的作用和寿命都得到了明确：某些 RNA 可以存活数周或更长时间。

Some RNAs (such as long noncoding RNAs, or lncRNAs) regulate gene expression by modifying DNA or its proteins.

一些 RNA（例如长非编码 RNA，或 lncRNA）通过修饰 DNA 或其蛋白质来调节基因表达。

Others, known as microRNAs, alter or repress other RNAs, including those that would otherwise be translated into proteins; this discovery was awarded the 2024 Nobel Prize in Physiology or Medicine .

其他被称为 microRNA 的 RNA 可以改变或抑制其他 RNA，包括那些原本会被翻译成蛋白质的 RNA；这一发现被授予2024年诺贝尔生理学或医学奖。

Could sperm carry RNA or other molecules that then participate in epigenetic processes in the embryo?

精子能否携带RNA或其他分子参与胚胎的表观遗传过程？

It seemed plausible to some researchers, but it would take a whole lot of experimental work to put the pieces together.

对于一些研究人员来说，这似乎是合理的，但需要进行大量的实验工作才能将这些碎片整合在一起。

There are three core questions that biologists need to resolve to confirm that sperm cells transmit epigenetic inheritance.

生物学家需要解决三个核心问题，以确认精子细胞能够传递表观遗传。

The first is how a father’s body physically encodes lived experience, such as stress, diet, exercise or nicotine use, in the form of molecules — for example, as RNAs circulating in blood that reflect gene expression in tissues.

第一个是父亲的身体如何以分子的形式对生活经历（例如压力、饮食、运动或尼古丁使用）进行物理编码——例如，作为血液中循环的RNA，反映组织中的基因表达。

The next centers on how molecularly encoded experience could make its way into sperm cells.

下一个重点是分子编码的经验如何进入精子细胞。

The third traces how those signals in sperm could become epigenetic vectors during and after fertilization to specify observable traits, known as phenotypes, in offspring.

第三个研究追踪了精子中的这些信号如何在受精期间和受精后成为表观遗传载体，以指定后代的可观察特征，即表型。

In a series of studies beginning in 2012, Qi Chen started answering all three questions.

在 2012 年开始的一系列研究中，陈奇开始回答这三个问题。

In what he describes as one of the most serendipitous discoveries of his career, his team at the Chinese Academy of Sciences in Beijing used sequencing techniques to inventory the short RNA molecules present in mice sperm cells.

他在北京中国科学院的团队使用测序技术清点了小鼠精子细胞中存在的短RNA分子，这是他职业生涯中最偶然的发现之一。

In 2012, Qi Chen found RNAs crowding into sperm heads with DNA.

2012年，陈琪发现RNA与DNA一起挤进精子头部。

He’s spent his career documenting what he calls the “sperm RNA code.”

他的整个职业生涯都在记录他所谓的“精子 RNA 代码”。

They were shocked to see a subset of the RNAs drastically increasing in concentration as sperm cells matured , and then crowding into the sperm heads with DNA.

他们震惊地发现，随着精子细胞的成熟，RNA 子集的浓度急剧增加，然后与 DNA 一起涌入精子头部。

This same class of RNAs was abundant in the blood serum of various vertebrates, ranging from fish to humans, they found.

他们发现，从鱼类到人类，各种脊椎动物的血清中都富含此类 RNA。

All of this pointed to the possibility that information-carrying molecules were being transferred into the reproductive cells.

所有这些都表明携带信息的分子可能被转移到生殖细胞中。

It got even more interesting when Chen, who moved to the U.S. academic circuit in 2015, and his team collected sperm RNAs from male mice fed different diets.

2015 年陈和他的团队从喂食不同饮食的雄性小鼠中收集精子 RNA 后，事情变得更加有趣。

The RNA assemblages in mice reared on high-fat foods differed dramatically from those in mice that were fed normal diets.

食用高脂肪食物的小鼠的 RNA 组合与正常饮食的小鼠的 RNA 组合有显着差异。

And when the researchers injected the RNAs from the sperm of the fat-eating mice into a zygote, some of the male offspring showed metabolic issues associated with a high-fat diet.

当研究人员将食脂小鼠精子中的 RNA 注入受精卵时，一些雄性后代出现了与高脂肪饮食相关的代谢问题。

The experiments hinted at a seemingly heretical possibility, Chen said: that “certain acquired traits during paternal exposure can be ‘memorized’ in the sperm and inherited by the offspring.” After characterizing a pathway that regulates sperm RNAs, in 2019 Chen dubbed this channel of heredity the “ sperm RNA code ,” which he suggested “programs the metabolic health of offspring.”

陈说，这些实验暗示了一种看似异端的可能性：“在父亲暴露期间获得的某些特征可以被‘记忆’在精子中，并由后代遗传。”在描述了一条调节精子 RNA 的通路后，陈于 2019 年将这种遗传通道称为“精子 RNA 代码”，他认为这“可以对后代的代谢健康进行编程”。

He wasn’t the only one to become fixated on this idea.

他并不是唯一一个痴迷于这个想法的人。

Around the same time, in an article published in Developmental Cell in 2018, Rando’s team reported the use of biochemical techniques to characterize where and when RNAs are packaged into sperm cells and how those RNAs might change during this process.

大约在同一时间，在 2018 年《Developmental Cell》杂志上发表的一篇文章中，Rando 的团队报告了使用生化技术来表征 RNA 被包装到精子细胞中的位置和时间，以及这些 RNA 在此过程中可能如何变化。

They were trying to answer the question: “What tissue could be responsible for choosing what to tell sperm to tell kids?” he said.

他们试图回答这个问题：“什么组织可以负责选择告诉精子告诉孩子什么？”他说。

One logical place to start looking was the epididymis.

一个合乎逻辑的开始寻找的地方是附睾。

Within this tubular organ attached to the back of the testicle, sperm cells undergo a maturation process, taking about one to two weeks in most mammalian species, before they become ready for fertilization.

在这个附着在睾丸背面的管状器官中，精子细胞经历成熟过程，在大多数哺乳动物物种中，在准备受精之前大约需要一到两周的时间。

Mark Belan/ Quanta Magazine ; source: International Journal of Molecular Sciences 21, 5377 (2020) ; BMC Biology 17, 35 (2019)

马克·贝兰/广达杂志；来源：国际分子科学杂志 21, 5377 (2020)； BMC 生物学 17, 35 (2019)

Mark Belan/ Quanta Magazine ; source: International Journal of Molecular Sciences 21, 5377 (2020) ; BMC Biology 17, 35 (2019)

马克·贝兰/广达杂志；来源：国际分子科学杂志 21, 5377 (2020)； BMC 生物学 17, 35 (2019)

Rando’s data showed that sperm cells gain almost all their small RNAs when they are in the epididymis.

Rando 的数据显示，精子细胞在附睾中获得几乎所有的小 RNA。

Using techniques for tracking specific RNA molecules, the scientists observed RNAs getting packaged into virus-size capsules, called epididymosomes, which shuttled the molecules into sperm.

利用追踪特定 RNA 分子的技术，科学家们观察到 RNA 被包装成病毒大小的胶囊，称为附睾体，将分子运送到精子中。

“This shows how small RNAs can get trafficked between the body’s nonreproductive cells, like those in the epididymis, and germline cells,” such as sperm, Rando said.

Rando 说：“这表明小 RNA 是如何在人体的非生殖细胞（如附睾中的细胞）和生殖细胞（如精子）之间运输的。”

“The epididymis has been emerging as a key location for paternal effects.

“附睾已成为父系效应的关键部位。

Certainly the epididymis has to be taken seriously as a potential sensor of the world.”

当然，必须认真对待附睾作为世界的潜在传感器。”

By “sensor of the world,” Rando is referring to the first stage of a presumed paternal-effects mechanism — when a male’s body translates a lived condition, such as a high-fat diet, rigorous exercise or toxin exposure, into molecular signals.

兰多所说的“世界传感器”指的是假定的父系效应机制的第一阶段——男性的身体将生活状况（例如高脂肪饮食、剧烈运动或毒素暴露）转化为分子信号。

The epididymis then provides a route for the second step, packaging those signals for the next generation.

然后附睾为第二步提供一条途径，为下一代包装这些信号。

This is also where investigations by Isabelle Mansuy come in.

这也是伊莎贝尔·曼苏伊展开调查的地方。

At the University of Zurich and the Swiss Federal Institute of Technology Zurich, she studies the molecular and cellular mechanisms of epigenetic inheritance in mammals.

在苏黎世大学和瑞士苏黎世联邦理工学院，她研究哺乳动物表观遗传的分子和细胞机制。

Isabelle Mansuy has traced the ways that consequences of stress from early life trauma alter metabolic pathways through five generations of mice.

伊莎贝尔·曼苏伊（Isabelle Mansuy）通过五代小鼠追踪了早年创伤造成的压力后果如何改变代谢途径。

© Philippe Rossier / Ringier Media Switzerland

© Philippe Rossier / 瑞士荣格媒体

In one line of her research, she focuses on processes that transmit the molecular effects of traumatic stress to subsequent generations by focusing on extracellular vesicles (EVs) that circulate in blood.

在她的一项研究中，她通过血液中循环的细胞外囊泡 (EV) 来研究将创伤应激的分子效应传递给后代的过程。

Shed by almost every type of cell in the body, including in the epididymis (the epididymosomes are EVs), they carry a diversity of molecular cargo, such as RNAs, proteins, lipids and metabolites.

体内几乎所有类型的细胞都会脱落，包括附睾（附睾小体是 EV），它们携带多种分子货物，如 RNA、蛋白质、脂质和代谢物。

Because EVs circulate in blood just about anywhere in the body and can cross cell membranes, they provide a potential means to transfer molecules and the biological cues they carry between bodily tissues and reproductive cells.

由于 EV 在血液中几乎在身体的任何地方循环，并且可以穿过细胞膜，因此它们提供了一种在身体组织和生殖细胞之间转移分子及其携带的生物信号的潜在手段。

Notably, RNAs tend to survive longer when packaged in EVs.

值得注意的是，RNA 包装在 EV 中时往往能存活更长时间。

Mansuy creates trauma in mice by subjecting the animals to conditions such as restraint or maternal separation when they are young.

曼苏伊在小鼠幼年时让它们受到束缚或与母体分离等条件，从而对小鼠造成创伤。

Then she searches for molecular changes in reproductive cells that could cause similar consequences of trauma to manifest in the children or even grandchildren of the animals who directly endure it.

然后，她寻找生殖细胞中的分子变化，这些变化可能会导致类似的创伤后果，并在直接承受创伤的动物的子代甚至孙代中显现出来。

She’s shown that traumatic stress alters metabolic pathways , especially those that involve lipids, in exposed male mice and their offspring.

她的研究表明，创伤性应激会改变暴露的雄性小鼠及其后代的代谢途径，尤其是那些涉及脂质的代谢途径。

She has also found a similar metabolic profile in humans who experienced high stress in childhood.

她还在童年经历过高压力的人类中发现了类似的代谢特征。

In mice, some of the metabolic changes remained discernible through five generations — a rare data-backed finding for epigenetic inheritance cascading through generations.

在小鼠中，一些代谢变化在五代中仍然可以辨别，这是表观遗传级联遗传的罕见数据支持的发现。

An egg cell is enormous compared to a sperm cell and contributes nearly all cellular components to a growing embryo — except the sperm’s half of the genome, and maybe embryonic and epigenetic regulators, according to recent research.

根据最近的研究，与精子细胞相比，卵细胞巨大，几乎为发育中的胚胎提供所有细胞成分——除了精子的一半基因组，以及可能的胚胎和表观遗传调节因子。

Dennis Kunkel Microscopy/Science Source

丹尼斯·昆克尔显微镜/科学来源

In March 2025, in a preprint uploaded to biorxiv.org , Mansuy and colleagues reported that EVs in mice can transport certain RNAs, metabolites and lipids linked to early-life stress from circulating blood to sperm, with consequences for offspring.

2025 年 3 月，Mansuy 及其同事在上传到 biorxiv.org 的预印本中报告说，小鼠中的 EV 可以将某些与早期生命压力相关的 RNA、代谢物和脂质从循环血液运输到精子，从而对后代产生影响。

The offspring produced by these sperm cells had stress-related metabolic dysfunction as adults and bore the stress signatures in their own sperm RNA.

这些精子细胞产生的后代成年后会出现与压力相关的代谢功能障碍，并且它们自己的精子 RNA 中也带有压力特征。

“These changes imply a mechanistic link between sperm RNA modifications and phenotypic features in the offspring,” Mansuy’s team concluded in their paper, which has not yet been peer-reviewed.

“这些变化意味着精子 RNA 修饰与后代表型特征之间存在机制联系，”Mansuy 的团队在他们的论文中得出结论，该论文尚未经过同行评审。

Perhaps the trickiest step to understand is how sperm-borne molecules could influence an adult’s observable traits.

也许最棘手的一步是了解精子携带的分子如何影响成年人的可观察特征。

In one form of experiment, researchers extract all the sperm RNA from mice that have been raised under stressful or health-altering conditions.

在一种实验中，研究人员从在压力或健康改变的条件下饲养的小鼠中提取了所有精子 RNA。

Those isolated RNAs are then injected into a zygote.

然后将这些分离的 RNA 注射到受精卵中。

Pups that emerge usually “get the dad’s phenotypes,” Conine said, suggesting that the RNAs alone confer traits from dad to offspring.

Conine 说，出生的幼崽通常会“继承父亲的表型”，这表明仅 RNA 就将父亲的特征赋予了后代。

But how?

但如何呢？

During early development, epigenetic processes reign .

在早期发育过程中，表观遗传过程占主导地位。

As one fertilized cell divides into two, and those cells divide again, and so on, one set of DNA instructions is dynamically and repeatedly reprogrammed.

当一个受精细胞分裂成两个，然后这些细胞再次分裂，依此类推，一组DNA指令被动态地、重复地重新编程。

The growing body specializes into different cell types and is sculpted into a sequence of increasingly complex forms.

不断生长的身体专门针对不同的细胞类型，并被雕刻成一系列日益复杂的形式。

It’s possible, then, that early epigenetic alterations to the genome could have significant downstream effects on an adult.

那么，基因组的早期表观遗传改变可能会对成年人产生显着的下游影响。

A team of researchers, including Xin Jin (top) and Xi Chen of Nanjing University, traced the epigenetic effects of paternal exercise in mice.

南京大学的金鑫（上）和陈曦等研究人员追踪了父亲运动对小鼠的表观遗传效应。

Research out of Conine’s lab, published in 2024, showed that sperm microRNAs alter gene expression in mouse embryos.

Conine 实验室于 2024 年发表的研究表明，精子 microRNA 会改变小鼠胚胎中的基因表达。

Experiments like these, he said, support the idea that offspring can inherit paternal traits via the transfer of non-DNA molecular stowaways in sperm.

他说，这样的实验支持了这样的观点，即后代可以通过精子中非 DNA 分子偷渡者的转移来遗传父系特征。

The recent Cell Metabolism paper took this idea a step further by tracing a mechanism by which this can happen.

最近的《细胞代谢》论文通过追踪这种情况发生的机制，将这一想法更进一步。

A team of more than two dozen Chinese researchers focused on the epigenetic transmission of exercise benefits, homing in on a set of microRNAs that reprogram gene expression in the early embryo.

一个由两打以上的中国研究人员组成的团队专注于运动益处的表观遗传传递，研究了一组在早期胚胎中重新编程基因表达的 microRNA。

These changes ultimately result in skeletal muscle adaptations in adult offspring that enhance exercise endurance.

这些变化最终导致成年后代的骨骼肌适应，从而增强运动耐力。

The researchers found that well-exercised mice had more of these microRNAs in their sperm than sedentary mice did.

研究人员发现，经常运动的小鼠精子中的这些 microRNA 比久坐的小鼠要多。

When these microRNAs were transferred into zygotes, the adults they grew into were more physically fit, with more mitochondria in skeletal muscle and higher endurance.

当这些 microRNA 被转移到受精卵中时，它们长大后的身体更加健康，骨骼肌中的线粒体更多，耐力也更高。

But how did the molecules generate the exercise-positive phenotype?

但这些分子是如何产生运动阳性表型的呢？

In experiments, the researchers found that the microRNAs suppressed a particular protein, which had the effect of boosting genes related to mitochondrial activity and metabolism.

在实验中，研究人员发现 microRNA 抑制了一种特定的蛋白质，这种蛋白质具有增强与线粒体活动和代谢相关的基因的作用。

Intriguingly, the sperm of physically trained male humans also hosted higher levels of many of the same microRNAs than those of untrained cohorts.

有趣的是，与未经训练的男性相比，经过体育训练的男性精子中许多相同的 microRNA 含量也更高。

“This cross-species conservation suggests a potential role for these sperm mi[cro]RNAs in intergenerational exercise adaptations in humans,” the researchers wrote.

研究人员写道：“这种跨物种保护表明这些精子 miRNA 在人类代际运动适应中具有潜在作用。”

The notion that a father’s lived experience can become recorded by his body, transmitted to his gametes and relayed to his offspring is no longer as outlandish as it once seemed.

父亲的生活经历可以被他的身体记录下来，传递给他的配子并传递给他的后代，这种想法不再像以前看起来那么奇怪。

Many researchers in the field are willing to float speculative visions of what could be going on, even as they acknowledge that gaps remain.

该领域的许多研究人员愿意对可能发生的事情提出推测性的看法，尽管他们承认差距仍然存在。

“Our hypothesis is that the epididymis ‘sees’ the world and alters the small RNAs it produces in response,” Rando said.

Rando 说：“我们的假设是，附睾‘看到’了世界，并改变了它产生的小 RNA 作为回应。”

“These RNAs are then delivered to the zygote upon fertilization and control early gene regulation and development to shape offspring health and disease.”

“然后这些 RNA 在受精时被传递到受精卵，并控制早期基因调控和发育，从而塑造后代的健康和疾病。”

Conine speculates that once certain RNAs make their way into the egg, they trigger “a cascade of changes in developmental gene expression that then leads to these phenotypes” of the father showing up in the next generation.

Conine 推测，一旦某些 RNA 进入卵子，它们就会引发“发育基因表达的一系列变化，从而导致父亲出现在下一代的这些表型”。

Remarkably, this unfolds even though the sheer volume of the sperm’s contents is so much less than an egg’s contents, including the relative amounts of RNA.

值得注意的是，尽管精子内容物的绝对体积（包括 RNA 的相对含量）远小于卵子的内容物，但这种情况仍然存在。

The full picture of how paternal experience and behavior might epigenetically influence offspring is not nearly in hand.

关于父亲的经历和行为如何对后代产生表观遗传影响的全貌尚不完全掌握。

Researchers are currently piecing the story together, one experiment at a time, rather than proving out every step sequentially in the same set of organisms.

研究人员目前正在将这个故事拼凑起来，一次一个实验，而不是在同一组生物体中按顺序证明每一步。

One of the gaps is in the characterization of what RNA and perhaps other epigenetic factors do in the zygote to modify genomic activity as it unfolds during development, Mansuy said.

Mansuy 说，其中一个差距在于对 RNA 和其他表观遗传因子在受精卵中在发育过程中如何改变基因组活性的表征。

“We are still blind men describing for the first time different parts of the same elephant,” Chen said.

“我们还是盲人，第一次描述同一头大象的不同部位，”陈说。

“The underlying mechanism is almost certainly an orchestra of a sperm RNA code and factors beyond that.”

“几乎可以肯定，潜在的机制是由精子 RNA 代码和其他因素组成的一个乐团。”

Confirming the findings in humans would take enormous effort, but it would be key to turning these findings in mice into “informed medical advice,” Chen said.

陈说，在人类身上证实这些发现需要付出巨大的努力，但将小鼠身上的这些发现转化为“知情的医疗建议”至关重要。

This would require well-controlled experiments following multiple generations, tracking diet, exercise, aging and environmental exposures, while also using advanced tools to decode sperm-packaged molecules — and then looking for strong correlations between the molecular and phenotypic data.

这需要在多代之后进行良好控制的实验，跟踪饮食、锻炼、衰老和环境暴露，同时还使用先进的工具来解码精子包装的分子，然后寻找分子和表型数据之间的强相关性。

Even amid the uncertainties, researchers are cautiously moving forward as they learn to believe the results of their own experiments.

即使存在不确定性，研究人员仍在谨慎地前进，因为他们学会相信自己的实验结果。

If they’re right, they will have discovered a new fact of life, Rando said.

兰多说，如果他们是对的，他们将发现生活的新事实。

When he thinks about his two boys, he wonders what he might have done differently when he was younger, before they were born, that might have tweaked his RNA profile in ways that would affect them today.

当他想起他的两个儿子时，他想知道在他们出生之前，他年轻时可能做了什么不同的事情，这可能会以影响他们今天的方式调整他的 RNA 谱。

“We don’t know enough yet to develop guidance like that,” Rando said.

“我们还不够了解，无法制定这样的指导，”兰多说。

“Maybe we will get there.”

“也许我们会到达那里。”

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辱骂、亵渎、自我推销、误导、语无伦次或偏离主题的评论将被拒绝。

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