Male contraceptive puts sperm to sleep

A new substance has the ability to turn sperm off for a few hours at a time.
24 February 2023

Interview with 

Melanie Balbach, Weill Cornell Medical College


Sperm surrounding an egg cell.


In the 1950s the European chemist Carl Djerassi changed the course of history, many argue, when he found a way to produce human sex hormones, including oestrogens and progesterones. These were subsequently turned into contraceptives, earning Djerassi the accolade of being “the father of the pill”, that’s since been taken by millions of women. And there contraception has largely remained ever since: as chiefly a female domain. Efforts have been made to generate male contraceptives, but this has proved to be a very hard nut to crack. Until now, perhaps. Because Cornell scientist Melanie Balbach and her colleagues have developed a drug that, taken half an hour beforehand, can temporarily immobilise sperm for at least a few hours, preventing them from fertilising eggs. Mice given the agent produced no pregnancies, but quickly recovered their fertility as soon as it was stopped.

Melanie - The idea is that the men take our pill 30 minutes before they have intercourse and that protective window will last about 24 hours and after that they get their fertility back.

Chris - So it's a reversible temporary interruption infertility.

Melanie - Exactly. So how it works is we're blocking the "on" switch in sperm. So what happens is, when the sperm are produced, they are stored in a tissue where they're sitting in a sleeping state and then when they are ejaculated they have to become motile and our target is responsible for that onset of motility for the sperm. So what we do is we inhibit that target so we stop it from being activated so the sperm remain imotile and they can't swim to the egg site and fertilise. What we're using to inhibit it is a chemical.

Chris - And that's what? A chemical that you found?

Melanie - Exactly. Our lab has been studying that “on” switch for 20 years. So we were actually looking for chemicals that would block it. So what we started with is something called a high throughput screen. What you essentially do is you have your target, your protein of interest, and there's actually a library of chemicals out there that you can look into and find the ones that are blocking your protein. And once we found such a chemical, we were further improving it to have the properties we need for a male contraceptive.

Chris - Is it selective? In other words, does it just hit sperm or does it hit other tissues? Because obviously one thing that has thwarted other efforts in this direction towards a male contraceptive have been off target side effects.

Melanie - That "on" switch and sperm actually also plays a role in other tissues. So our inhibitor, our chemical, can affect the protein there theoretically as well. But what is different in all these other tissues and organs, all the other organs have a sister protein that has the same function. So in all the other organs, even if our protein is blocked, those other tissues will still be okay because they still have that sister enzyme or that sister protein working. Whereas in the sperm exclusively our protein is responsible. So that's why we have such a stronger effect in the sperm than anywhere else.

Chris - How did you test that? Because obviously this has not gone into humans yet. How have you figured out that this is what it does?

Melanie - We did studies in mice and the first thing I did is I looked at their sperm and what I found is that the sperm of those male mice were not swimming. Their motility was inhibited after 15 minutes and then that lasted about three hours and then it slowly came back and by 24 hours their motility was completely back to normal. So then the second thing I did was mating experiments. So I gave that inhibitor to the male mice and then I paired them with females and then I checked if those females were pregnant. And again with that first window of three hours, we did not get any pregnancies with the females. And then when I kept the males and the females together for longer, I slowly got pregnancies and then, by 24 hours, it was a normal pregnancy rate again in both females.

Chris - It's amazing. It's a very, very powerful effect isn't it? If you've got no pregnancies at all, especially with mice because they're pretty fertile. What about will it work in humans? That's obviously the critical question.

Melanie - So we are very optimistic that it will because of two things: one thing is that that protein we have been talking about actually has the same function in human sperm as in mouse sperm. And the second thing is that I can take sperm from human donors and I can add our chemical to the sperm. And what I see there is that the human sperm stops swimming there.


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