Mammalian gametes—the sperm and the egg—represent opposite extremes of cellular organization and scale. Studying the ultrastructure of gametes is crucial to understanding their interactions, and how to manipulate them in order to either encourage or prevent their union. Here, we survey the prominent electron microscopy (EM) techniques, with an emphasis on considerations for applying them to study mammalian gametes. We review how conventional EM has provided significant insight into gamete ultrastructure, but also how the harsh sample preparation methods required preclude understanding at a truly molecular level. We present recent advancements in cryo-electron tomography that provide an opportunity to image cells in a near-native state and at unprecedented levels of detail. New and emerging cellular EM techniques are poised to rekindle exploration of fundamental questions in mammalian reproduction, especially phenomena that involve complex membrane remodelling and protein reorganization. These methods will also allow novel lines of enquiry into problems of practical significance, such as investigating unexplained causes of human infertility and improving assisted reproductive technologies for biodiversity conservation.

哺乳动物的配子——精子和卵子——代表了细胞组织和规模的两个极端。研究配子的超微结构对于理解它们的相互作用以及如何操纵它们以鼓励或阻止它们的结合至关重要。在这里，我们调查了著名的电子显微镜（EM）技术，重点是应用它们研究哺乳动物配子的考虑因素。我们回顾了传统电镜如何提供对配子超微结构的重要洞察，以及苛刻的样品制备方法如何阻碍真正分子水平的理解。我们介绍了冷冻电子断层扫描的最新进展，这些进展提供了以接近天然状态和前所未有的细节水平对细胞进行成像的机会。新兴的细胞电镜技术有望重新激发对哺乳动物生殖基本问题的探索，特别是涉及复杂膜重塑和蛋白质重组的现象。这些方法还将允许对具有实际意义的问题进行新的研究，例如调查人类不孕的不明原因和改进辅助生殖技术以保护生物多样性。