Scanning electron microscopy of zebrafish eggs inseminated with mouse sperm close the micropyle canal (right panel) and traversing (left and center panels). Garibova et al. (CC BY 4.0)
Conception begins when a sperm cell fuses with an egg cell in a process called fertilization, initiating the development of a genetically unique embryo. This fundamental event is conserved among vertebrates, although the cellular environments and molecular mechanisms involved vary across taxa, especially between mammals and externally fertilizing fish.
In mammals, sperm must first bind to and penetrate the zona pellucida, a matrix surrounding the egg. They then attach to the membrane underneath, called the oolemma, and initiate fusion. In teleost fish, by contrast, the egg is surrounded by a structurally distinct extracellular envelope called the chorion. Unlike mammalian sperm, fish sperm do not bind directly to this barrier. Instead, they gain access to the egg through a narrow, funnel-shaped canal called the micropyle.
Until recently, it was widely believed that the mechanisms that help the sperm recognize and respond to eggs were specific to different species and incompatible across distant taxa. However, Garibova et al. provided evidence that some of the signalling cues guiding sperm towards the eggs may be conserved across vertebrates.
The researchers investigated whether mouse sperm can recognize and respond to the structural features of zebrafish eggs. To test whether mouse sperm could locate and enter the micropyle, they used time-lapse imaging, as well as confocal and electron microscopy.
The results revealed that while mouse sperm did not bind to the fish chorion, they could locate and enter the zebrafish micropyle. Moreover, a subset of mouse sperm actively swam toward and across the micropyle, a behavior analogous to that of zebrafish sperm, which become active only in proximity to egg cells.
Further molecular analysis revealed that sperm cells needed to be hyperactive to complete their passage through the chorion. This hyperactivity was regulated by a calcium channel called CatSper. Using sperm from mutant mice lacking CatSper, the cells were unable to reach or cross the micropyle. These findings suggest that despite differences in egg coats between mammals and fish, the ways sperm find and navigate toward the egg may rely on evolutionarily conserved mechanisms.
Such discoveries could aid scientists and clinicians working in assisted reproductive technologies in humans, as well as in companion and farm animals, by providing insights into the molecular mechanisms underlying sperm guidance and egg recognition. To enable clinical or agricultural translation of these findings, future studies should identify the molecular mediators governing sperm guidance and micropyle recognition. Functional validation through loss-of-function assays in transgenic fish and mouse models will be crucial to determine whether these mechanisms are truly conserved across taxa. A deeper understanding could inform the development of novel sperm selection strategies or contraceptive approaches aimed at modulating gamete interaction.
