Artificial Sperm

Artificial Sperm

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Ian Lecklitner
January 12, 2018

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Your testicles may soon be obsolete
Welcome to the future: Researchers recently took an important step forward in mimicking how the human body produces sperm, and could one day (likely 10 or so years from now) create artificial, lab-grown sperm and eggs for infertility treatment.
It’s all quite science-y, but here’s the gist, according to The Guardian :
Speaking at the Progress Educational Trust annual conference in London this month, Azim Surani, director of germline and epigenetics research at the University of Cambridge’s Gurdon Institute, said he and colleagues had passed a significant milestone on the path to producing sperm in the laboratory. The team is thought to be the first to have reached the halfway point on the developmental path from human stem cells to immature sperm.
The study hints that one day it may be possible to manufacture sperm and eggs from stem cells or even adult skin cells.
How are the researchers attempting to create this artificial sperm?Paulson: Human stem cells can be differentiated into any cell in the body—that includes brain cells, kidney cells and also reproductive cells (like sperm). In this case, the question is: How do you entice a stem cell to become a sperm cell instead of a brain cell, for instance? These researchers created an artificial gonad to help the original stem cell decide to become a sperm.
Normally, these stem cells come from one of two places: There are embryonic stem cells, which come from the inner cell mass of a human embryo. But more often nowadays, we use induced pluripotent stem cells , which can be taken from any cell in the body. For example, they can derive stem cells from a little piece of skin.
What might we use artificial sperm for in the future? Paulson: Let’s say I want to reproduce, but I had some sort of accident that resulted in losing my testicles. Scientists could hypothetically take a few of my skin cells, turn them into stem cells, and then turn those stem cells into sperm. From there, I could use in vitro fertilization to become a father.
Here’s another example: If two people of the same sex want to have a child, scientists could make an egg out of one stem cell and a sperm out of another stem cell. Say you have two women: One might use her own eggs, and scientists could make sperm using skin cells from the other woman. This would allow them to reproduce.
Barritt: This could technically be useful for a person who transitioned from female to male, and wants to be able to produce sperm as well. Scientists also would be able to produce sperm cells that could then be used to help figure out why fertility is declining, and what goes wrong. In other words, we could use these sperm cells for research and testing, which is important because we can’t simply take a testicle out of someone for fun.
Are there any dangers that come with using it? Paulson: The DNA must be retained in these sperm, which is tricky, because the sperm should only contain half of our DNA. We each have 46 chromosomes—23 from our mother and 23 from our father. So when you create a sperm cell, you have to throw half of the chromosomes (23) away, and there will be problems if that’s done incorrectly. Those sperm would produce nonviable offspring.
Barritt: The things that can go wrong in the process of epigenetics [heritable changes in gene expressions] can lead to things like Prader-Willi syndrome or Angelman syndrome . There are probably many other genes that are important to this process, and if they’re not right, they may lead to genetic issues that we don’t even know about yet.
Would artificial sperm allow people more control over how their child turns out? Paulson: Not much more than we currently have. Today, you can go to a sperm bank to collect sperm from whoever has donated, and analogously, you can go to an egg bank to collect an egg from whoever has donated. Artificial sperm might make this process a little easier: These people wouldn’t have to donate sperm or eggs, only their skin cells.
Would it be possible for someone to create sperm from cells picked up from anyone, anywhere? Say, taking a cell from a celebrity without their knowledge? Paulson: The idea that this is going to create abnormal children—or that someone might steal some of your skin cells to produce a child that looks like you—is a little far-fetched.
Barritt: You won’t be able to simply pull some DNA from a counter. To go through this process, you would have to give them enough cells to populate the artificial gonad and go through an eight-week process. Of course, there needs to be legal control to ensure no one does anything against someone’s consent. However, you would really have to be consenting and wanting to do this, because it’s a lot of work and will require time and money.
Could this ever become our go-to method for making babies? Barritt: The natural way is the human favorite for the time being. But here’s a thought: Aging in women leads to more genetic problems, which leads to a decrease in fertility. The truth is, men actually do go through a very similar process—it doesn’t occur nearly as fast or as harshly, but there is something called advanced paternal age. There’s some literature that claims genetic mutations—like autism—may come from men of an older age, which may be because the cells in their bodies that produce sperm accumulate genetic problems over time.
If men of an older age want to reproduce, they could put non-sperm cells through this process, and therefore it wouldn’t be an older cell that produces the sperm. It would be a nice young cell, which would therefore decrease the potential of advanced paternal age effects. In that way, it may become a standard for advanced-age men.
Ian Lecklitner is a staff writer at MEL Magazine. He mostly writes about everyone's favorite things: Sex, drugs and food.

Unlike these guys, artificial sperm don't have tails. Credit: Sebastian Kaulitzki/Shutterstock.com

Check out this great content before you leave
Scientists have used embryonic stem cells to grow the most effective 'test-tube' sperm cells ever, demonstrating how they can be used to fertilise mouse eggs, and produce healthy, fertile offspring.
The cells are the first in the world to meet a set of criteria known as the 'gold standard' for artificial sperm, set by three fertility researchers in 2014. "The achievements of this paper are very remarkable," John Schimenti of Cornell University, one of the researchers who defined the gold standard, told New Scientist. "I'm not aware of another group having progressed this far."
The team from Nanjing Medical University in China haven't used stem cells to create actual, proper sperm cells, but they have managed to create artificial spermatids, which are immature versions of sperm that have not yet grown tails. Without tails, these spermatids can't swim, so they're injected into a mouse egg via IVF instead.
To reach the gold standard for artificial sperm, the researchers had to demonstrate that at various stages of growth, the cells were retaining a number of crucial characteristics, such as the right number of chromosomes and the right percentage of donor DNA. And that's no easy feat, as every other attempt to adequately control all the key stages of sex cell division has failed.
"Until now, researchers have struggled to prove that they have pushed cells through an important but complicated dividing process that leaves cells with only half of the father's chromosomes," Andy Coghlan reports for New Scientist.
So not only has the team appeared to master the cell division process, they were also able to produce healthy offspring - two factors that helped them meet the elusive gold standard.
"We think our work is the first to monitor and examine all requirements for successful meiosis," said one of the team, Jiahao Sha .
So how did they do it? The researchers took embryonic stem cells from male mice and exposed them to chemicals called cytokines that triggered their transformation into germ cells - a type of cell that gives rise to sex cells (eggs or sperm). While the cells were differentiating, they were placed next to testes-like tissue and exposed to the male sex hormone, testosterone, to coax them into a spermatid form.
The technique has so far only been tested on mice, so we have no idea if it'll work on humans dealing with fertility problems. But the hope is that one day, scientists could extract cells from an infertile man - such as skin or cheek cells - revert them to an embryonic stem cell-like state, and then convert those into artificial spermatids for use in IVF.
And this isn't such a crazy proposition, as Akshat Rathi reports over at Quartz : "Past research has shown that skin cells can be converted into pluripotent stem cells, which are equivalent to embryonic stem cells. These pluripotent stem cells have even been converted into precursors of sperm and egg cells."
While this could work in theory, the ethical questions of doing so means we're a very long way off actually using the technique to create humans.
"How can we tell if spermatids made in a laboratory are really of the same high quality as those made and tested by natural selection in the testis?" biologist Peter Donovan from the University of California, Irvine, who was not involved in the study, pointed out to The Verge .
Just as allowing babies to be born from genetically modified embryos brings up some serious concerns about 'designer babies' bypassing the natural order of things, if artificial sperm were used to create humans, we would have to reconcile the problem of whether or not they are inherently disadvantaged in some way, and that's no easy question to answer.
But with researchers in France and Japan following close on the heels of Sha and his team in the race towards artificial human sperm, we're going to have to figure it out sooner rather than later.
The results have been published in Cell Stem Cell.

Unlike these guys, artificial sperm don't have tails. Credit: Sebastian Kaulitzki/Shutterstock.com

Check out this great content before you leave
Scientists have used embryonic stem cells to grow the most effective 'test-tube' sperm cells ever, demonstrating how they can be used to fertilise mouse eggs, and produce healthy, fertile offspring.
The cells are the first in the world to meet a set of criteria known as the 'gold standard' for artificial sperm, set by three fertility researchers in 2014. "The achievements of this paper are very remarkable," John Schimenti of Cornell University, one of the researchers who defined the gold standard, told New Scientist. "I'm not aware of another group having progressed this far."
The team from Nanjing Medical University in China haven't used stem cells to create actual, proper sperm cells, but they have managed to create artificial spermatids, which are immature versions of sperm that have not yet grown tails. Without tails, these spermatids can't swim, so they're injected into a mouse egg via IVF instead.
To reach the gold standard for artificial sperm, the researchers had to demonstrate that at various stages of growth, the cells were retaining a number of crucial characteristics, such as the right number of chromosomes and the right percentage of donor DNA. And that's no easy feat, as every other attempt to adequately control all the key stages of sex cell division has failed.
"Until now, researchers have struggled to prove that they have pushed cells through an important but complicated dividing process that leaves cells with only half of the father's chromosomes," Andy Coghlan reports for New Scientist.
So not only has the team appeared to master the cell division process, they were also able to produce healthy offspring - two factors that helped them meet the elusive gold standard.
"We think our work is the first to monitor and examine all requirements for successful meiosis," said one of the team, Jiahao Sha .
So how did they do it? The researchers took embryonic stem cells from male mice and exposed them to chemicals called cytokines that triggered their transformation into germ cells - a type of cell that gives rise to sex cells (eggs or sperm). While the cells were differentiating, they were placed next to testes-like tissue and exposed to the male sex hormone, testosterone, to coax them into a spermatid form.
The technique has so far only been tested on mice, so we have no idea if it'll work on humans dealing with fertility problems. But the hope is that one day, scientists could extract cells from an infertile man - such as skin or cheek cells - revert them to an embryonic stem cell-like state, and then convert those into artificial spermatids for use in IVF.
And this isn't such a crazy proposition, as Akshat Rathi reports over at Quartz : "Past research has shown that skin cells can be converted into pluripotent stem cells, which are equivalent to embryonic stem cells. These pluripotent stem cells have even been converted into precursors of sperm and egg cells."
While this could work in theory, the ethical questions of doing so means we're a very long way off actually using the technique to create humans.
"How can we tell if spermatids made in a laboratory are really of the same high quality as those made and tested by natural selection in the testis?" biologist Peter Donovan from the University of California, Irvine, who was not involved in the study, pointed out to The Verge .
Just as allowing babies to be born from genetically modified embryos brings up some serious concerns about 'designer babies' bypassing the natural order of things, if artificial sperm were used to create humans, we would have to reconcile the problem of whether or not they are inherently disadvantaged in some way, and that's no easy question to answer.
But with researchers in France and Japan following close on the heels of Sha and his team in the race towards artificial human sperm, we're going to have to figure it out sooner rather than later.
The results have been published in Cell Stem Cell.

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