Lab-grown human sperm cells could unlock treatments for infertility

Dr. Miles Wilkinson: Photo courtesy UCSD

Out of 100 couples in the US, around 12 or 13 will have trouble starting a family. In one third of those cases the problem is male infertility (one third is female infertility and the other third is a combination of factors). In the past treatment options for men were often limited. Now a new study out of the University of California San Diego (UCSD) could help lead to treatments to help these previously infertile men have children of their own.

The study, led by Dr. Miles Wilkinson of UCSD School of Medicine, targeted spermatogonial stem cells (SSCs), which are the cells that develop into sperm. In the past it was hard to isolate these SSCs from other cells in the testes. However, using a process called single cell RNA sequencing – which is like taking a photo of all the gene expression happening in one cell at a precise moment – the team were able to identify the SSCs.

In a news release Dr. Wilkinson, the senior author of the study, says this is a big advance on previous methods: “We think our approach — which is backed up by several techniques, including single-cell RNA-sequencing analysis — is a significant step toward bringing SSC therapy into the clinic.”

Identifying the SSCs was just the first step. Next the team wanted to find a way to be able to take those cells and grow and multiply them in the lab, an important step in having enough cells to be able to treat infertility.

So, they tested the cells in the lab and identified something called the AKT pathway, which controls cell division and survival. By blocking the AKT pathway they were able to keep the SSCs alive and growing for a month. Next they hope to build on the knowledge and expand the cells for even longer so they could be used in a clinical setting.

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Illustrations by Vishaala Wilkinson

The hope is that this could ultimately lead to treatments for men whose bodies don’t produce sperm cells, or enough sperms cells to make them fertile. It could also help children going through cancer therapy which can destroy their ability to have children of their own later in life. By taking sperm cells and freezing them, they could later be grown and expanded in the lab and injected back into the testes to restore sperm production.

The study is published in the journal Proceedings of the National Academy of Science.

Our Tainted Food Supply: Its Lasting Effects on Stem Cells May Explain Declines in Sperm Counts

Spermatozoons, floating to ovuleIn the science fiction film, Children of Men, humans in the year 2027 face extinction due to decades of infertility. This premise doesn’t seem all that far-fetched when you consider studies in the U.S., Japan, and Europe over the past two decades that point to declining sperm counts. A 2013 study, for instance, that followed 26,000 French men for 17 years reported a 32% drop in sperm counts. And a study of 5000 Danish men with a median age of 19 found 40% had sperm counts corresponding to infertility or decreased fertility.

So what’s going on here? One line of evidence blames exposure to chemicals that leach into our food and water supply. A possible culprit is the much-despised Bisphenol-A, or BPA, a man-made chemical found in plastic bottles, the inner linings of canned food and even receipt paper used at your local grocery store. BPA is known as a hormone disruptor because it interferes with normal hormone activity in the body by mimicking the female hormone estrogen. Lab animals exposed to low levels of BPA have shown increased incidence of certain cancers, neurological problems, diabetes, obesity, female reproduction problems and, yes, decreased sperm counts.

BPA_shutterstock_243369064Data published last week in PLOS Genetics appears to have pinpointed the link between BPA and decreased sperm counts: stem cells. Specifically the so-called spermatogonial stem cells that give rise to sperm. In the Washington State University study, the research team gave newborn male mice daily oral doses of BPA for about two weeks. The chemical exposure negatively affected this spermatogonial stem cell population by disrupting the processing of the cells’ DNA and, in turn, the development of fully mature sperm. The team got similar results replacing BPA with synthetic estrogen found in birth control pills. This form of estrogen is also known to contaminate our water supply even after sewage treatment.

A surprising and even scary twist to these results is that the brief exposure of BPA or estrogen in the newborn male mice permanently changed their stem cells. The team confirmed this observation by transplanting the spermatogonial stem cells from BPA-exposed mice into the testes of mice that never received BPA. In this case, these mice still exhibited reduced sperm production. As senior author Nancy Hunt points out in an interview with Scientific American, the exposure to these chemicals:

“is not simply affecting sperm being produced now, but impacting the stem cell population, and that will affect sperm produced throughout the lifetime.”

It’s remains debatable whether the detectable BPA or estrogen levels in our food and water supply is high enough to actually cause health problems in humans. In 2013 the Food and Drug Administration (FDA) downplayed possible worries on its website:

“Is BPA safe? Yes. Based on FDA’s ongoing safety review of scientific evidence, the available information continues to support the safety of BPA for the currently approved uses in food containers and packaging.”

Still, this recent study and others like it certainly warrant further investigation. University of Missouri scientist Frederick vom Saal, who was not part of the study, put it this way in his interview with Scientific American:

“It’s important in future studies to see if the stem cell changes from exposure are passed to future generations… Since most people are consistently exposed to BPA and other estrogenic compounds, each generation could have it a bit worse.”