Some semelparous organisms in nature mate as many times as they can in a single reproductive episode before death, while most iteroparous species including humans avoid such suicidal reproductive behavior. Animals naturally pursue more sex and the possible fatal consequence of excessive sex must be orchestrated by negative feedback signals in iteroparous species, yet very little is known about the regulatory mechanisms. Here we used Drosophila male sexual behavior as a model system to study how excessive sex may kill males and how the nervous system reacts to prevent death by sex. We found that continuous sexual activity by activating the fruitless-expressing neurons induced a fixed multi-step behavioral pattern ending with male death. We further found negative feedback in the fly brain to prevent suicidal sexual behavior by expression changes of the neurotransmitters acetylcholine and gamma-aminobutyric acid, and neuropeptide F. These findings are crucial to understand the molecular underpinnings of how different organisms choose reproductive strategies and balance reproduction and survival.

自然界中的一些半生生物在死亡前的一次生殖过程中会尽可能多地交配，而包括人类在内的大多数反复生的物种都会避免这种自杀性的生殖行为。动物自然会追求更多的性行为，过度性行为可能导致的致命后果必须由迭代生育物种的负反馈信号精心策划，但对调节机制知之甚少。在这里，我们使用果蝇雄性性行为作为模型系统来研究过度性行为如何杀死雄性以及神经系统如何反应以防止性行为死亡。我们发现持续的性活动通过激活无用的-表达神经元诱导固定的多步行为模式，以男性死亡结束。我们进一步发现苍蝇大脑中的负反馈通过神经递质乙酰胆碱和γ-氨基丁酸以及神经肽 F 的表达变化来防止自杀性行为。这些发现对于了解不同生物如何选择繁殖策略和平衡繁殖的分子基础至关重要和生存。