First steps toward male infertility treatment

March 28, 2017 by Grant Hill, University of Dundee
Credit: University of Dundee

Scientists from the University of Dundee believe they have taken the first steps towards developing drugs to treat infertile men.

Infertility is a significant problem affecting tens of millions of couples worldwide, with around half of cases having a male factor either as a sole or contributory cause. It is known that asthenozoospermia (poor/dysfunctional motility) is the commonest disorder in male infertility, yet there is no drug that men can currently take for it to improve the chances of conception.

As such, couples who require assistance to conceive need to rely on clinical treatments such as In vitro fertilisation (IVF) or (ICSI), both of which are expensive, invasive and are not guaranteed to work.

While there is clearly an unmet need for alternative treatments for male subfertility, the time, effort and resources required for drug discovery are currently exorbitant. The cellular, physical and functional properties of human spermatozoa present unique challenges to researchers and the lack of an appropriate platform to analyse potential treatments further complicates the issue.

Now the Dundee team have developed and validated a high throughput screening (HTS) method that may help to find novel agents that improve sperm function. HTS automates the experimentation process to allow researchers to quickly identify active compounds, antibodies, or genes relevant to their work.

While a cure for remains some way off, the researchers, led by Dr Sarah Martins da Silva, believe their method has removed many of the barriers towards developing drugs to treat the condition.

"Male infertility is incredibly common but there is nothing we can currently prescribe in the vast majority of cases," said Dr Martins da Silva. "The problem is that we really don't understand how sperm function. And because we don't really understand how they function, then we don't know how to correct sperm dysfunction either.

"The other issue is that sperm are absolutely unique cells, designed to survive outside the body and hugely specialised to swim, find and fertilise an egg. They are small and have virtually no cytoplasm, and the cell signalling pathways can be unlike other cells. As a result, sperm are incredibly challenging to study. We believe we have now taken the first steps towards helping millions of couples worldwide."

It is known that alterations in intracellular calcium are fundamental to sperm function, including swimming and fertilisation, and that fluctuations in calcium are due, in large part, to a sperm-specific channel named CatSper (Cation channel of sperm).

In the absence of a known specific molecular or receptor target, compound library high-throughput screening (HTS) is an alternative approach that has developed in recent decades.

Dr Martins da Silva and her colleagues worked with the University's Drug Discovery Unit (DDU) to create a high-throughput assay platform to monitor intracellular calcium responses in sperm as a surrogate for sperm motility.

"This enabled us to identify hit compounds, which we were able to test on sperm and saw improved functional motility," continued Dr Martins da Silva. "We also saw enhanced functional motility when we tested two of the compounds on patient samples, which is exciting and hugely relevant for patients, albeit this is still very early days."

As the CatSper channel is unique to sperm, identifying a therapeutic compound for it potentially avoids systemic side-effects, making these candidates very attractive both clinically and commercially.

Having concluded that HTS can robustly and efficiently identify novel compounds that increase intracellular calcium in human spermatozoa and improve function, the researchers propose to use it as a cornerstone to drive forward for male subfertility.

The paper has been published online by the Human Reproduction journal.

Explore further: Males conceived via fertility treatment may have weakened sperm: study

More information: Sarah J. Martins da Silva et al. Drug discovery for male subfertility using high-throughput screening: a new approach to an unsolved problem, Human Reproduction (2017). DOI: 10.1093/humrep/dex055

Related Stories

Males conceived via fertility treatment may have weakened sperm: study

October 7, 2016
(HealthDay)—Males who were conceived using an infertility treatment where sperm is injected into an egg may themselves have lower sperm quantity and quality than those conceived naturally, Belgian researchers report.

Some sunscreen ingredients may disrupt sperm cell function

April 1, 2016
Many ultraviolet (UV)-filtering chemicals commonly used in sunscreens interfere with the function of human sperm cells, and some mimic the effect of the female hormone progesterone, a new study finds. Results of the Danish ...

Study reveals gene's role in male infertility

October 13, 2016
A Virginia Commonwealth University-led research team has opened a fresh direction in the field of male infertility with a new study that examines the role of a particular gene in the formation of sperm flagella, which is ...

New sperm research could lead to cut in infertility rate

October 31, 2016
Sperm and mathematics don't appear to be the likeliest of bedfellows - but new research bringing the two together could lead to devices that could cut infertility rates.

Recommended for you

Exercise-induced hormone irisin triggers bone remodeling in mice

December 13, 2018
Exercise has been touted to build bone mass, but exactly how it actually accomplishes this is a matter of debate. Now, researchers show that an exercise-induced hormone activates cells that are critical for bone remodeling ...

Law professor suggests a way to validate and integrate deep learning medical systems

December 13, 2018
University of Michigan professor W. Nicholson Price, who also has affiliations with Harvard Law School and the University of Copenhagen Faculty of Law, suggests in a Focus piece published in Science Translational Medicine, ...

Drug targets for Ebola, Dengue, and Zika viruses found in lab study

December 13, 2018
No drugs are currently available to treat Ebola, Dengue, or Zika viruses, which infect millions of people every year and result in severe illness, birth defects, and even death. New research from the Gladstone Institutes ...

Faster test for Ebola shows promising results in field trials

December 13, 2018
A team of researchers with members from the U.S., Senegal and Guinea, in cooperation with Becton, Dickinson and Company (BD), has developed a faster test for the Ebola virus than those currently in use. In their paper published ...

Pain: Perception and motor impulses arise in brain independently of one another

December 13, 2018
Pain is a negative sensation that we want to get rid of as soon as possible. In order to protect our bodies, we react by withdrawing the hand from heat, for example. This action is usually understood as the consequence of ...

Researchers give new insight to muscular dystrophy patients

December 13, 2018
New research by University of Minnesota scientists has revealed the three-dimensional structure of the DUX4 protein, which is responsible for the disease, facioscapulohumeral muscular dystrophy (FSHD). Unlike the majority ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.