What happens if you mix fish eggs and mouse sperm?

Updated on 01 Dec 2025 | Category: Science

What happens if you mix mouse sperm with fish eggs? In his quest to discover the signals that guide sperm to eggs and drive fertilisation, that was the experiment that Matteo Avella, from Qatar University, carried out. And despite millions of years of evolution separating the two species, there was clear evidence that the sperm were interacting with a specific structure on the

What happens if you mix mouse sperm with fish eggs? In his quest to discover the signals that guide sperm to eggs and drive fertilisation, that was the experiment that Matteo Avella, from Qatar University, carried out. And despite millions of years of evolution separating the two species, there was clear evidence that the sperm were interacting with a specific structure on the fish eggs called the micropyle, which is a hole in the egg surface coat that - in fish - allows sperm entry. As Chris Smith hears, the discovery opens the door now to track down how these signals are conveyed and interpreted by both entities, with obvious implications for better understanding the fertilisation process, infertility and assisted conception…
Matteo - So, the main question we asked was a quite fundamental one: can sperm from one species recognise and respond to the egg of another? And so, in mammals like mice or humans, fertilisation takes place inside the female reproductive tract, and sperm must bind to a layer around the egg, which is called the zona pellucida. But, interestingly, in mammals, including the mouse, we still don't have a clearly defined mechanism that actively attracts sperm to the egg. We know that sperm eventually reach it, but we don't know how they navigate so precisely within the female genital tract.
Chris - That is actually a real phenomenon, is it? So, if you actually do experiments, you can prove that there is an attractive force guiding sperm towards eggs; it's not just random, it's not just mass action - so many sperm that some inevitably stumble on the target...?
Matteo - Right, that's an open question, and that's one cool aspect of this research we performed. We were actually able to identify for the first time a discrete mechanism that mammalian sperm use to locate an oocyte.
Chris - How did you go about exploring this then? Because haven't people been looking at this question for a really long time because of the obvious implications for fertility, fertility treatment, infertility, etc?
Matteo - At the beginning, we wanted to test what was an assumption in the field. So, in fish, the egg is surrounded by an outer layer called the chorion. Fish sperm do not bind to the chorion. They actually use an opening in the chorion. This opening is called a micropyle. And so, the fish sperm cross the chorion by using this micropyle. And you imagine the micropyle to be as a hole in the chorion. This chorion is defined by a number of proteins. They are called zona pellucida proteins. They are not like the ones that are present in a mouse or in humans, but they are evolutionarily related. No one has ever tested whether this fish zona proteins actually are able to support sperm binding. It was always assumed that they cannot because fish sperm do not bind to the chorion. Hence, they should not bind to these zona proteins. So, that's why we wanted to test it.
Chris - What did you do then? Incubate mouse sperm with fish eggs to see if the fish egg would influence the mouse sperm in the same way that a mouse egg might influence mouse sperm?
Matteo - Yes, correct. We wanted to see whether mouse sperm are able or not to recognise the fish egg outer layer. So, we co-incubated mouse sperm with the fish eggs and found that they were able to recognise the opening, the micropyle, the same opening that the fish sperm recognised before crossing the chorion and fusing with it.
Chris - That's surprising, isn't it? Because, obviously, a mouse and a fish are millions of years of evolution apart, and mice don't have that structure. So that argues they've retained that capacity. But how do you know that the mice sperm were actually recognising that structure? What was the giveaway that there was some interaction going on between the micropyle - this hole in the fish egg - and the sperm going into it?
Matteo - That is a great question. We took a number of time-lapse imaging movies where we were able to show that actually not all the sperm were able to locate the micropyle but just a fraction of it. And it appeared to be that this fraction of sperm that were actually able to locate the micropyle and enter through the micropyle were sperm that present this changing motility pattern called hyperactive motility. And this hyperactive motility is essential in mammalian fertilisation for sperm to acquire if they want to be able to cross the egg envelope and finally fuse with the egg.
Chris - Were these sperm getting activated by the fish egg or in order to have that hyper motility that would normally do this? Or did some of them just by chance happen to have that already and that is what enabled those particular groups that had just randomly become hypermotile to get in?
Matteo - Another great question. So, we will be able to answer this question once we identify these proteins surrounding the micropyle, the opening, and the molecular identity of this protein is still undefined. Then we will be able to assess whether this protein is actually capable of inducing hyperactivation in mammalian sperm.
Chris - Obviously mice do not have these openings - these micropylar openings - that fish eggs do, but the sperm have retained their sensitivity to it and the proteins that perhaps adorn it. Are you arguing, then, that really the role of that protein and that response to the protein has now been redeployed by evolution so that it is attracting a mouse sperm to a mouse egg even though there is no micropylar opening there for them to go through, because they will instead get to the egg and then try and break through that outer shell, that zona pellucida they have to get through in order to fertilise the egg?
Matteo - You are absolutely correct, Chris. This is a very good point. To address these great points we will have to identify the micropylar protein first and once we know what the molecular identity of this micropylar protein is then we will be able to see whether this protein is present also in the mouse egg and where in the mouse egg this protein is localised, is expressed, and in that case we'll be able to establish animal models or mouse models that do not have this protein and see whether fertilisation rate is affected also. But all these questions will have to be addressed once this micropylar protein will be molecularly identified.
Chris - Presumably, thinking ahead, there might be a link then to infertility, because we know that in some cases sperm just don't seem to get into eggs. So could it be that it's something going wrong with this process that, in those subset of cases of infertility, that might be going on? So if you can identify what the protein is, you can then ask well is it linked to the reason that the sperm don't get in in this context?
Matteo - Almost certainly, Chris. So there are cases of unexplained infertility where couples present both normal looking sperm and eggs but for some reasons they don't fertilise and so they require assisted reproduction and in vitro fertilisation. And so if such a mechanism is considered cross-evolution and such protein exists in mammals as it does in fish then mutations that prevent the expression of this protein will likely lead or affect the fertility.