Naked mole-rat queens use a chemical signal to suppress fertility in rivals

裸鼹鼠女王利用化学信号抑制竞争者的生育能力

Naked mole rats are weird. They spend their lives almost entirely underground, are largely insensitive to some kinds of pain, can persist without oxygen for a long time, rarely develop cancer, and can live past 30 years, which is decades longer than similarly sized rodents. They are also eusocial, like ants, bees, or termites—in a colony that can hold more than a hundred animals, only one female, the queen, breeds. 裸鼹鼠是一种奇特的生物。它们几乎终生生活在地下，对某些疼痛几乎没有感觉，能在缺氧环境下长时间生存，极少患癌，且寿命可超过30年，这比体型相当的啮齿动物长了几十年。它们还具有真社会性，就像蚂蚁、蜜蜂或白蚁一样——在一个可能容纳上百只个体的群体中，只有一只雌性，即女王，能够进行繁殖。

We didn’t know how exactly naked mole-rat queens stop other females from breeding. For a long time, our leading hypothesis was bullying and violence, but that may be a bit impractical, given their kingdoms are vast networks of tunnels that can stretch for up to three kilometers. But now a team of Lewin Lab scientists at Max Delbrück Center for Molecular Medicine in Berlin discovered it’s actually just one part of a sophisticated olfactory signaling program. 我们此前并不清楚裸鼹鼠女王究竟是如何阻止其他雌性繁殖的。长期以来，我们的主要假设是霸凌和暴力，但考虑到它们的王国是由长达三公里的庞大隧道网络组成的，这种方式似乎不太现实。然而，柏林马克斯·德尔布吕克分子医学中心（Max Delbrück Center for Molecular Medicine）Lewin实验室的科学家团队发现，这实际上只是一个复杂嗅觉信号系统的一部分。

Running on smell

依靠嗅觉运行

“It’s very clear that mole rats actually have quite big noses and smell a lot,” says Gary Lewin, a neurobiologist at the Max Delbrück Center for Molecular Medicine and senior author of the study. Naked mole rats have around 1200 olfactory receptor genes, more than mice (which have roughly 1,000 of them) and way more than the few hundred in humans. They’re also blind. “They have to be able to navigate and move around without vision, so smell is one of those things that’s enhanced,” Lewin said. “很明显，裸鼹鼠的鼻子很大，嗅觉非常灵敏，”该研究的资深作者、马克斯·德尔布吕克分子医学中心的神经生物学家Gary Lewin表示。裸鼹鼠拥有约1200个嗅觉受体基因，多于小鼠（约1000个），更远超人类的几百个。它们还是盲的。“它们必须在没有视觉的情况下进行导航和移动，因此嗅觉是它们增强的能力之一，”Lewin说。

To find out how heavily mole rats rely on smell, the team collected odor bouquets from individual animals. Scientists held an absorbent plastic tube near a mole rat for about half an hour to pick up the volatile molecules coming off its body. Then, they analyzed these scents in a mass spectrometer, which separated the components of the scent into around 100 distinct chemical compounds. 为了探究裸鼹鼠对嗅觉的依赖程度，研究团队收集了不同个体的气味样本。科学家将一根吸收性塑料管放在裸鼹鼠附近约半小时，以采集其身体散发的挥发性分子。随后，他们利用质谱仪对这些气味进行分析，将气味成分分离成约100种不同的化学化合物。

Based on analyzing samples taken from hundreds of different mole rats, the team learned members of each colony carried a distinguishable chemical signature. When mole rats from different colonies were placed together, they sniffed each other for about 40 seconds to decide if they were dealing with their nestmate or a stranger. When they sniffed a stranger, they attacked, often with lethal intent. “Naked mole rats are like humans in the sense that they’re very xenophobic,” Lewin said. 通过对数百只不同裸鼹鼠的样本进行分析，研究团队发现每个群体的成员都带有可辨识的化学特征。当来自不同群体的裸鼹鼠被放在一起时，它们会互相嗅探约40秒，以判断对方是同巢伙伴还是陌生个体。一旦嗅出对方是陌生者，它们就会发起攻击，且往往带有致命意图。“裸鼹鼠和人类很像，它们非常有排外性，”Lewin说。

So, the team tested if depriving mole-rats of smell would purge the xenophobia out of them. It did. When scientists temporarily disabled mole-rats’ olfactory sensory neurons with chemicals, the aggression towards strangers disappeared. “They basically were cool with each other, and there was no fighting,” Lewin said. 因此，研究团队测试了剥夺裸鼹鼠的嗅觉是否能消除这种排外性。结果确实如此。当科学家利用化学物质暂时阻断裸鼹鼠的嗅觉感觉神经元后，它们对陌生个体的攻击性消失了。“它们基本上能和平相处，没有发生任何争斗，”Lewin说。

Besides chemical friend-or-foe signals, researchers found something else in the odor bouquets. There was one compound, an ester called isopropyl myristate, that scientists found in the samples taken from queens and nowhere else. “Breeding females had this particular molecule that non-breeding animals did not have,” Lewin said. 除了辨别敌友的化学信号外，研究人员还在气味样本中发现了其他东西。科学家在女王的样本中发现了一种名为肉豆蔻酸异丙酯（isopropyl myristate）的酯类化合物，而在其他个体中并未发现。“繁殖期的雌性拥有这种非繁殖个体所没有的特殊分子，”Lewin说。

The royal scent

女王的气味

Scientists found breeding queens secreted isopropyl myristate from their genitals and smeared it through the tunnels as they roamed their underground kingdoms. Tracking a queen’s output of the compound over her reproductive cycle showed that it rises and falls with her fertility, peaking when she’s in heat or pregnant. “It’s actually a very good marker of whether the queen is capable of breeding,” Lewin said. 科学家发现，处于繁殖期的女王会从生殖器分泌肉豆蔻酸异丙酯，并在其地下王国巡游时将其涂抹在隧道中。追踪女王在整个繁殖周期内该化合物的分泌情况显示，其含量随生育能力波动，在发情或怀孕时达到峰值。“这实际上是判断女王是否具备繁殖能力的一个非常好的指标，”Lewin说。

On top of that, it has another useful feature. Isopropyl myristate, while volatile, is rather stable once deposited on a surface. Researchers could still detect it in mole-rat cages roughly 24 hours after it’d been applied. Because a colony’s burrow system can run up to three kilometers, a queen has a lot of ground to cover if she wants every subordinate exposed to her scent. “It sticks around for a while, so she has less work to spread the odor around the underground colony,” Lewin said. 此外，它还有另一个有用的特性。肉豆蔻酸异丙酯虽然具有挥发性，但一旦附着在表面上就相当稳定。研究人员在涂抹约24小时后仍能在裸鼹鼠笼中检测到它。由于一个群体的洞穴系统可长达三公里，如果女王想让每一只从属个体都接触到她的气味，她需要覆盖的范围非常广。“它能留存一段时间，所以她不必费力就能将气味散布到整个地下群体中，”Lewin说。

Pinpointing the queen’s molecule was one thing, though. Showing what it does was another. 然而，确定女王的这种分子是一回事，证明它的作用则是另一回事。

Lowborns and upstarts

低位者与僭越者

Naked mole-rat colonies are organized in a hierarchy loosely correlated with body size, starting with bottom-ranked workers and foragers, up through soldiers, to the highest-ranked animals and the breeding male called the pasha. Scientists sort naked mole rats into ranks using a dominance test: When two animals meet in a tunnel, whichever one yields is the lower-ranked of the pair. 裸鼹鼠群体按照与体型大致相关的等级制度组织，从底层的工鼠和觅食鼠，到兵鼠，再到最高等级的个体以及被称为“帕夏”（pasha）的繁殖雄鼠。科学家通过支配测试对裸鼹鼠进行分级：当两只个体在隧道中相遇时，退让的一方即为等级较低者。

When Lewin’s team tested how mole rats react to isopropyl myristate, the reaction seemed to be dependent on rank. When placed in a T-maze with the queen’s molecule placed on one side, higher-ranked females, the ones with a realistic shot at becoming the queen one day, avoided it. “We’ve got an idea, although we didn’t prove it, that in a normal environment, higher-ranked animals try to avoid the queen, because the queen might be aggressive towards them,” Lewin said. 当Lewin的团队测试裸鼹鼠对肉豆蔻酸异丙酯的反应时，发现反应似乎取决于等级。当被放置在T型迷宫中，且一侧涂有女王的分子时，等级较高的雌性——即那些未来有希望成为女王的个体——会避开它。“我们有一个想法，尽管尚未证实：在正常环境中，高等级个体试图避开女王，因为女王可能会对它们表现出攻击性，”Lewin说。

Direct evidence on the mole-rat brain response to isopropyl myristate came from functional ultrasound imaging, a technique that tracks blood flow non-invasively in an anesthetized animal. “If you just puff isopropyl myristate on the nose of the animal, a large part of the olfactory cortex lights up,” Lewin said. The team interpreted this as a proof the compound is registering as a distinct signal, not just background smell. 关于裸鼹鼠大脑对肉豆蔻酸异丙酯反应的直接证据来自功能性超声成像，这是一种在麻醉动物身上无创追踪血流的技术。“如果你对着动物的鼻子喷洒肉豆蔻酸异丙酯，嗅觉皮层的大部分区域就会亮起，”Lewin说。研究团队将其解读为该化合物被识别为一种独特信号的证据，而不仅仅是背景气味。

What’s more, the exposure to the queen’s scent triggered hormonal shifts in females. Non-breeding mole-rat females are known to run high on prolactin, a hormone that also suppresses fertility during lactation in nursing mammals. Lewin’s team found that prolactin levels drop when a queen is removed from a colony and climb back up once isopropyl myristate is reintroduced. Progesterone, a hormone associated with active breeding, moved in the opposite direction: low in non-breeders, and rising once the queen was gone. “These hormones seem to be directly controlled by the presence of the molecule [isopropyl myristate].” 此外，接触女王的气味会引发雌性体内的激素变化。已知非繁殖期的雌性裸鼹鼠催乳素水平较高，这种激素在哺乳动物哺乳期也会抑制生育能力。Lewin的团队发现，当女王从群体中移除时，催乳素水平会下降，而一旦重新引入肉豆蔻酸异丙酯，水平又会回升。与活跃繁殖相关的孕酮激素则呈现相反趋势：在非繁殖个体中较低，而在女王离开后上升。“这些激素似乎直接受到该分子[肉豆蔻酸异丙酯]存在与否的控制。”