Gene Editing Stops Sperm Production In Mice Raising Hopes For Male Contraceptive

by NCN Health And Science Team Posted on October 12th, 2017

The results of a new study funded in part by the US National Institutes of Health and the Michigan State
AgBioResearch showed that researchers at the Michigan State University using gene editing successfully turned off the gene in mice that controlled their sperm production, rendering them infertile, raising hopes for an elusive effective contraception for men using gene editing to stop the production of sperm. The results was published this week in the journal Nature Communications.

The new method interferes with genes responsible for creating new sperm. This approach would be a onetime affair that did not involve messing hormonal regulations that led to several side effects and needed men to remember to take pills regularly or at least get hormonal shots at regular intervals.

The Only side effect of this gene editing technique in men is that it could lead to shrunken testes.

Michigan State animal research team led by biologist Chen Chen first isolated and then selectively blocked a gene in mice that controlled their sperm production. The gene is question comes for an enzyme called PNLDC1. This enzyme controls the movement of transposons during sperm production. Transposons or “jumping genes” are those bits or sequences of the genes that can copy themselves to other parts of the genome randomly and lead to harmful mutations. These jumping genes are thus controlled by a bit of RNA which in turn is controlled by PNLDC1. For this study the researchers removed the gene that codes for PNLDC1 in mice using CRISPR. This led to uncontrolled jumping genes and eventually stoppage of production of healthy sperms.

The offspring of these mice who had the blocked gene had fewer sperms and were rendered sterile. Their testicles too were smaller. The growth, appearance and behaviour of the genetically modified mice was not altered at all explained the researchers except for the smaller testicles. Chen Chen explained that this method was analogous to fixing a water leak. Till date the approaches we had were just like stuffing a rag into the leak and hoping it stems the flow. This new method works by turning off the water supply to the tap!

Another issue here is the potential for reversibility of fertility if the person wants. That is also yet to be studied. According to experts, one good this that has come out of this study is the identification of what PNLDC1 does. If an inhibitor of PNLDC1 could be developed, it could do the job. Safety and efficacy of such an agent though is still up for debate as of now.

That being said, this trial took place in mice. The effects of editing this particular gene in humans are unknown. Gene editing with CRISPR in humans is still in the very early stages, and it would likely be years before any gene editing contraceptive trials in humans got underway.

Now that researchers know what PNLDC1 does, they could potentially develop an inhibitor that targets the enzyme and disrupts its function. Even a more conventional treatment like this would still need to be examined for side effects, though.

The researchers didn’t test for reversibility here, but they would need to show that they could do it, and that sperm returned to normal levels afterward. Some previous options for male birth control, like the herb gossypol, tested in the 1970s, effectively lowered sperm counts, but proved to permanently affect sperm production in some men.

In recent years, CRISPR has gained a reputation as one of the most effective approaches to gene editing.

Here are eight things to know about CRISPR and its potential influence on disease prevention.

1. CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, is a gene-editing technology that enables scientists to edit an organism’s — such as a human’s — DNA. The CRISPR system allows scientists to add, remove and replace segments of genetic material within a living organism’s genome, according to the National Institutes of Health’s Genetic Home Reference guide.

2. CRISPR is based on the gene-editing systems bacteria use to defend against viruses. Bacteria create DNA segments known as “CRISPR arrays” based on “snippets” of DNA from a virus, according to the NIH guide. The bacteria use these DNA segments to produce RNA that targets the virus. In a laboratory setting, researchers are likewise able to create RNA that targets a specific DNA sequence and enzyme within the genome.

3. Many scientists consider the CRISPR-Cas9 system — which creates modified RNA segments that bind to the CRISPR-associated protein 9 enzyme — to be one of the most precise and least expensive gene-editing techniques. Unlike other approaches, the CRISPR-Cas9 system is able to cut DNA segments without additional tools and can target multiple genes at the same time, according to a guide created by Cambridge, Mass.-based Broad Institute of MIT and Harvard.

4. In a study published in Nature Biotechnology Feb. 6, a team of researchers used gene-editing tech to enable mice suffering from hereditary deafness to hear. In a separate study published in Nature Aug. 2, researchers used CRISPR-Cas9 to “correct” a gene mutation in human embryos that causes hypertrophic cardiomyopathy, a genetic heart disease that sometimes leads to sudden cardiac death and heart failure.

5. Some researchers think CRISPR might hold the key to disease prevention for a variety of medical conditions. In a 2015 study published in Nature Biotechnology, researchers explained a targeted technique they engineered to disrupt genes related to select mosquitos’ fertility in an effort to one day “suppress mosquito populations to levels that do not support malaria transmission.”

6. In 2015, Science named CRISPR its “breakthrough of the year.” “The biomedical applications of CRISPR are just starting to emerge,” the magazine published at the time. “In short, it’s only slightly hyperbolic to say that if scientists can dream of a genetic manipulation, CRISPR can now make it happen.” The technology has continued to gain popularity as additional research findings about its uses are published.

7. However, despite CRISPR boasting one of the most precise approaches, gene-editing technology also comes with its risks. In a study published in Nature Methods June 14, a research team noted they witnessed “unexpected mutations” in secondary genes while attempting to use CRISPR-Cas9 to restore sight in blind mice.

8. As CRISPR’s advancements have begun to unfold, ethical concerns over the misuse of gene editing have also grown.

Scientists have long feared the unforeseen medical consequences of making inherited changes to human DNA. Some experts have warned that unregulated genetic engineering may lead to a new form of eugenics, in which people with means pay to have children with enhanced traits even as those with disabilities are devalued.

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