Retroviruses invading the koala germline contribute to high cancer rates

Koalas are facing multiple environmental and health issues which threaten their survival. Along with habitat loss – accelerated by last year’s devastating bush fires – domestic dog attacks and road accidents, they suffer from deadly chlamydial infections and extremely high frequency of cancer.

An international team of scientists led by the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) now demonstrate that a retrovirus invading the koala germline explains the high frequency of koala cancer. The results are reported in the journal Nature Communications.

The koala retrovirus (KoRV) is a virus that, like other retroviruses such as HIV, inserts itself into the DNA of an infected cell. At some point in the past 50,000 years, KoRV has infected the egg or sperm cells of koalas, leading to offspring that carry the retrovirus in every cell in their body.

The entire koala population of Queensland and New South Wales in Australia now carry copies of KoRV in their genome. All animals, including humans, have gone through similar "germline" infections by retroviruses at some point in their evolutionary history and contain many ancient retroviruses in their genomes.

These retroviruses have, over millions of years, mutated into degraded, inactive forms that are no longer harmful to the host. Since in most animal species this process occurred millions of years ago, the immediate health effects on the host at that time are unknown but it has been suspected for some time that the invasion of a genome by a retrovirus may have considerable detrimental health effects.

The koala is at a very early stage of this process when the retrovirus is still active and these health effects can be studied.

Since retroviruses can cause cancer, it was thought that there is a link between KoRV and the high frequency of lymphoma, leukaemia and other cancers in koalas from northern Australia. To investigate this link, scientists at the Leibniz-IZW sequenced DNA from wild koalas suffering from cancer.

This allowed them to accurately detect the number of copies of KoRV in the koala genomes and identify the precise locations where the retrovirus had inserted its DNA. By comparing this information between healthy and tumour tissues in single koalas, and by comparing insertion sites between koala individuals, they found multiple links between KoRV and genes known to be involved in the kind of cancers to which koalas are prone.

"Each koala carries around 80 – 100 inherited copies of KoRV in its genome. The genomic locations of most of these are not shared between koalas, indicating a rapid expansion and accumulation of KoRV copies in the population. Each time a retrovirus copies and re-inserts itself into the genome, it causes a mutation, potentially disrupting gene expression, which could be detrimental to the host," says Prof Alex Greenwood, Head of Department of Wildlife Diseases at the Leibniz-IZW.

This means that by frequently copying itself to new locations in the genome, KoRV is currently conferring a high mutational load on the koala population. Tumour tissues contain many new copies of KoRV, indicating that KoRV is more active in tumour cells.

These copies generally were located close to genes associated with cancer. New KoRV insertions in tumour tissues affected the expression of genes in their vicinity. Such changes in gene expression associated with cancer can cause increased cell growth and proliferation, which leads to tumours.

Although other factors may also contribute to cancer in koalas, the mutational burden from KoRV likely increases the frequency of cells becoming cancerous and may shorten the time for cancer to develop.

In one koala, a copy of KoRV was found that had incorporated an entire cancer-related gene from the koala genome into its DNA sequence. This greatly increased the expression of this gene and most likely caused cancer in this particular koala.

If this mutated virus is transmissible, it would be of grave concern for koala conservation efforts. Comparing the genomic location of KoRVs between koalas also suggests that KoRV may predispose related koalas to particular tumours, with koalas sharing KoRV insertions in specific cancer-related genes suffering from similar types of cancer which they can pass on to their offspring.

Across all koalas studied, there were "hot spots" in the genome where KoRV frequently inserts itself. These hot spots were also located in proximity to genes associated with cancer.

In summary then, we find multiple links at the genomic level between cancer-related genes and KoRV, revealing ways in which KoRV underlies the high frequency of cancer in koalas."

Gayle McEwen, Scientist, Leibniz Institute for Zoo and Wildlife Research (IZW)

The results highlight the detrimental health consequences that wildlife species can suffer following germline infection by retroviruses.

Germline invasions have been repeatedly experienced during vertebrate evolution and have shaped vertebrate genomes, including the lineage leading to modern humans. These were most likely associated with severe detrimental health effects, which must be endured and overcome to ensure species survival.

The scientists at the Leibniz-IZW have previously shown that old retroviruses present in the koala genome aid the rapid degradation of KoRV. The koala finds itself in a race to survive the effects of KoRV long enough for the virus to be degraded. Considering the many threats to koalas, it is a race they need to win.

Source:

Leibniz Institute for Zoo and Wildlife Research (IZW)

Journal reference:

McEwen, G. K., et al. (2021) Retroviral integrations contribute to elevated host cancer rates during germline invasion. Nature Communications. doi.org/10.1038/s41467-021-21612-7.

Posted in: Genomics | Life Sciences News

Tags: Cancer, Cell, DNA, Evolution, Frequency, Gene, Gene Expression, Genes, Genome, Genomic, Germline, HIV, Leukemia, Lymphoma, Mutation, Proliferation, Research, Retrovirus, Sperm, Virus

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Male Condom versus Female Condom

Condoms are essentially a barrier method of contraception. The concept is that if the sperm can be prevented from entering the uterus, it will not be able to fertilize the egg leading to protection against pregnancy. Both male and female condoms are available in the market. They are to be thrown away after a single use. Here we explore the differences between them.

The male condom

The male condom is used over the man’s erect penis. It may be made of latex, polyurethane or polyisoprene. For those allergic to latex, there are specialized condoms made out of lambskin available. The male condom has the distinction of being the most common contraceptive used by couples worldwide.

In addition to providing protection from conception, the male condom is also able to shield the user from sexually transmitted infections such as HIV, chlamydia and gonorrhoea. This is especially useful for those having sexual intercourse with multiple partners.

The female condom

The female condom is pushed inside the vagina as a lining or a artificial pocket. It is made of polyurethane or nitrile polymer which is a synthetic rubber. It looks like a lubricated pouch with two ends, one of which is open and the other closed. Both the ends have flexible stiff rings at the ends which help to keep the female condom in place after insertion.

While it is believed that female condoms may also provide protection against sexually transmitted infections, it is not as effective as the male condom as some body fluids may be exchanged. Inserting the female condom properly into the vagina needs to be practised so that it is placed correctly. Also the shifting of the pouch of the female condom during sexual intercourse is considered to be normal.

Which is more effective?

There are many contraception methods that a couple in a sexual relationship may choose to use. However, for quick contraception the condoms appear to be the fastest-acting choice. When used properly, both male and female condoms are highly effective in preventing an unwanted pregnancy.

No contraception method is 100% effective, but condoms do tend to do a good job on the whole. There is a 21% chance of becoming pregnant while using the female condom. This is considerably higher than the 14% chance of pregnancy while using a male condom.  You can only use one of the condoms at a time. Male and female condoms cannot be used together. However, other contraceptives such as spermicides or the oral contraceptive pill can be used with either the male or the female condom.

However, there are instances when the condoms tear or rupture during sexual intercourse, which may lead to accidental pregnancy. The barrier method, in general, has a 12 to 28% failure rate as per the National Institutes of Health. This includes the use of contraceptive sponges, diaphragms and cervical caps as well as condoms.

The male condom is more effective than the female condom at preventing pregnancy. This is probably because it is easier to place on the erect penis rather than inserting a female condom into the vagina and ensuring that the inner ring hits the cervix.

Disadvantages of using condoms

Some condom users, though by no means all, report that using this method of conception can reduce the sensitivity  of the genital organs and inhibit pleasure during sexual intercourse.

Condoms cannot be used for spontaneous sexual intercourse. The person must disengage from the partner to put on the condom once intercourse is about to take place.

No condom is fool proof. Incorrect usage or rupture during use can result in failure of the barrier contraceptive method.

People allergic to latex are unable to use regular condoms. The lambskin or polyurethane condoms are more expensive, but may be used in place of regular condoms.

The female condom may be pushed inside the vagina during sexual intercourse. This will also cause the condom to lose some efficiency in preventing pregnancy.

The rings of the female condom have been known to cause irritation inside the vagina, as well as to the male penis. This may be remedied with the use of extra lubrication. If irritation persists, the user should check for an allergic reaction.

Advantages of using condoms

Using condoms perfectly is the best way to avoid getting a sexually transmitted infection. Of course the one method that works all the time is abstinence!

Condoms can be easily bought at regular grocery stores and do not require a prescription like some other conception methods do. This makes them readily accessible to many people.

The female condom has the advantage of staying in place even after sexual intercourse, unlike male condoms which may slide off when the male loses his erection. This means that there is no accidental spilling of sperm inside the vagina, unlike what happens when the male condoms slides off the penis while the male organ is still inside the vagina.

The use of condoms allows both male and female partners to take responsibility for avoiding unwanted pregnancy in a simple manner.

References

  1. https://www.dred.com/uk/types-of-contraceptives.html
  2. https://www.nichd.nih.gov/health/topics/contraception/conditioninfo/Pages/types.aspx
  3. http://www.fpa.org.uk/contraception-help/condoms-male-and-female
  4. http://www.pamf.org/teen/sex/birthcontrol/condom.html
  5. http://www.pamf.org/teen/sex/birthcontrol/femalecondom.html

Further Reading

  • All Contraception Content
  • Advantages and Disadvantages of the Contraceptive Patch
  • Advantages and Disadvantages of the Contraceptive Implant
  • Advantages and Disadvantages of the Contraceptive Vaginal Ring
  • Do Contraceptive Injections Affect Bones?
More…

Last Updated: Aug 23, 2020

Written by

Cashmere Lashkari

Cashmere graduated from Nowrosjee Wadia College, Pune with distinction in English Honours with Psychology. She went on to gain two post graduations in Public Relations and Human Resource Training and Development. She has worked as a content writer for nearly two decades. Occasionally she conducts workshops for students and adults on persona enhancement, stress management, and law of attraction.

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Sperm don’t swim anything like we thought they did, new study finds

Under a microscope, human sperm seem to swim like wiggling eels, tails gyrating to and fro as they seek an egg to fertilize. 

But now, new 3D microscopy and high-speed video reveal that sperm don’t swim in this simple, symmetrical motion at all. Instead, they move with a rollicking spin that compensates for the fact that their tails actually beat only to one side. 

“It’s almost like if you’re a swimmer, but you could only wiggle your leg to one side,” said study author Hermes Gadêlha, a mathematician at the University of Bristol in the U.K. “If you did this in a swimming pool and you only did this to one side, you would always swim in circles. … Nature in its wisdom came [up] with a very complex, ingenious way to go forward.” 

Strange swimmers

The first person to observe human sperm close up was Antonie van Leeuwenhoek, a Dutch scientist known as the father of microbiology. In 1677, van Leeuwenhoek turned his newly developed microscope toward his own semen, seeing for the first time that the fluid was filled with tiny, wiggling cells. 

Under a 2D microscope, it was clear that the sperm were propelled by tails, which seemed to wiggle side-to-side as the sperm head rotated. For the next 343 years, this was the understanding of how human sperm moved. 

“[M]any scientists have postulated that there is likely to be a very important 3D element to how the sperm tail moves, but to date we have not had the technology to reliably make such measurements,” said Allan Pacey, a professor of andrology at the University of Sheffield in England, who was not involved in the research. 

The new research is thus a “significant step forward,” Pacey wrote in an email to Live Science. 

Gadêlha and his colleagues at the Universidad Nacional Autónoma de México started the research out of “blue-sky exploration,” Gadêlha said. Using microscopy techniques that allow for imaging in three dimensions and a high-speed camera that can capture 55,000 frames per second, they recorded human sperm swimming on a microscope slide. 

“What we found was something utterly surprising, because it completely broke with our belief system,” Gadêlha told Live Science. 

The sperm tails weren’t wiggling, whip-like, side-to-side. Instead, they could only beat in one direction. In order to wring forward motion out of this asymmetrical tail movement, the sperm head rotated with a jittery motion at the same time that the tail rotated.The head rotation and the tail are actually two separate movements controlled by two different cellular mechanisms, Gadêlha said. But when they combine, the result is something like a spinning otter or a rotating drill bit. Over the course of a 360-degree rotation, the one-side tail movement evens out, adding up to forward propulsion.

“The sperm is not even swimming, the sperm is drilling into the fluid,” Gadêlha said. 

The researchers published their findings today (July 31) in the journal Science Advances.

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Asymmetry and fertility

In technical terms, how the sperm moves is called precession, meaning it rotates around an axis, but that axis of rotation is changing. The planets do this in their rotational journeys around the sun, but a more familiar example might be a spinning top, which wobbles and dances about the floor as it rotates on its tip. 

“It’s important to note that on their journey to the egg that sperm will swim through a much more complex environment than the drop of fluid in which they were observed for this study,” Pacey said. “In the woman’s body, they will have to swim in narrow channels of very sticky fluid in the cervix, walls of undulating cells in the fallopian tubes, as well have to cope with muscular contractions and fluid being pushed along (by the wafting tops of cells called cilia) in the opposite direction to where they want to go. However, if they are indeed able to drill their way forward, I can now see in much better clarity how sperm might cope with this assault course in order to reach the egg and be able to get inside it,” Pacey said

Sperm motility, or ability to move, is one of the key metrics fertility doctors look at when assessing male fertility, Gadêlha said. The rolling of the sperm’s head isn’t currently considered in any of these metrics, but it’s possible that further study could reveal certain defects that disrupt this rotation, and thus stymy the sperm’s movement. 

Fertility clinics use 2D microscopy, and more work is needed to find out if 3D microscopy could benefit their analysis, Pacey said. 

“Certainly, any 3D approach would have to be quick, cheap and automated to have any clinical value,” he said. “But regardless of this, this paper is certainly a step in the right direction.”

Originally published in Live Science.

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