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Germ Cells Protected From Damage By A Class Of RNA Molecules

 

chlamydia transmission Passing one's genes on to the next generation is a mark of evolutionary success. So it makes sense that the body would work to ensure that the genes the next generation inherits are exact replicas of the originals.




New research by biologists at the University of Pennsylvania School of Veterinary Medicine has now identified one way the body does exactly that. This protective role is fulfilled in part by a class of small RNA molecules called pachytene piwi-interacting RNAs, or piRNAs. Without them, germ-cell development in males comes to a halt. Because these play such an important role in allowing sperm to develop normally, the research indicates that defects in these molecules or the molecules with which they interact may be responsible for some cases of male infertility.




Jeremy Wang, an associate professor of developmental biology and director of the Center for Animal Transgenesis and Germ Cell Research at Penn Vet, and Ke Zheng, a postdoctoral researcher in Wang's lab, authored the study, which appears in PLOS Genetics.




Scientists know of 8 million different piRNAs in existence; they are the most abundant type of small non-coding RNA. The molecule piRNA gets its name because it forms complexes with piwi proteins. Earlier work had indicated that these piwi-piRNA complexes suppress the activity of transposable elements or "jumping genes," which are stretches of DNA that can change position and cause potentially damaging genetic mutations. These sequences are also known as transposons.




"There are about 50 human diseases caused by transposable elements, so it's important for the body to have a way to try to repress them," Wang said.




This transposon-suppressing activity had been confirmed in a group of piRNAs called pre-pachytene piRNAs, which are expressed before meiosis, the unique process by which germ cells divide. But Zheng and Wang wanted to investigate if a separate group of piRNAs that emerge during meiosis, called pachytene piRNAs, were also required for "silencing" transposons.




Working in male mice, the researchers manipulated an enzyme called MOV10L1, which is known to interact with piwi proteins and is believed to help produce piRNA molecules. They created a mutant mouse in which they could selectively inactivate MOV10L1 at specific stages before, during and after meiosis. The mice that lost the function of MOV10L1 before or at the pachytene stage of meiosis were sterile. When Zheng and Wang examined their germ cells more closely, they found that spermatogenesis had apparently come to a halt at the post-meiotic stage: Early stages of the germ cells were present, but the mice completely lacked mature sperm.




Further experiments allowed Zheng and Wang to pinpoint that MOV10L1 was playing a critical role at the pachytene stage. MOV10L1 mutants lacked pachytene piRNAs, but their levels of pre-pachytene piRNAs were unaffected, as the mutation was "turned on" after they had already been produced.




The researchers also found that, in the MOV10L1 mutants, piwi proteins congregated together along with mitochondria, suggesting that mitochondria may be involved in the generation or organization of pachytene piRNAs. Furthermore, the spermatids, or early-stage sperm, of the mutants had severe DNA damage. While the researchers suspected that the damage may have been caused because of transposons that had been freed from repression in the absence of piRNAs, they actually found that two common transposable elements were not de-repressed in the mutants. They also found a build-up of pachytene piRNA precursors in the testes of the mutants. Their findings raise the possibility that there is another mechanism by which damage occurs.




"It could be the accumulation of precursor molecules is causing some of the damage," Wang said.




This new function for MOV10L1, in playing an essential role in producing pachytene piRNAs, gives researchers a greater understanding of germ-cell development.




"This is the first time we've shown that pachtyene piRNA is required for maintaining genome integrity in the post-meiotic germ cells," Wang said. "It turns out that MOV10L1 is a master regulator of the piRNA pathway and is required for the production of all piRNAs, both pre-pachytene and pachytene."




Any disruptions to this "master regulator" role, therefore, could lead to problems.




"I think we're just beginning to appreciate the significance of this pathway," Wang said. "Mutations at various points in the pathway could lead to infertility."


Female Condom to Protect Against STD

 

chlamydia transmission A female condom developed by researchers not only provides contraception but also wards off sexually transmitted diseases (STDs).




Researchers at the University of Washington (UW) developed the condom from tiny microfibres through a method called 'electrospinning'. They are then designed to dissolve after use, either within minutes or over several days.




Not only would the condom block sperm, it could time-release a potent mix of anti-HIV drugs and hormonal contraceptives, the Daily Mail reported.




Kim Woodrow, assistant professor of bio-engineering at Washington, said: "Our dream is to create a product women can use to protect themselves from HIV infection and unintended pregnancy. We have the drugs to do that. It's really about delivering them in a way that makes them more potent, and allows a woman to want to use it."




Woodrow presented the idea, and co-authors Emily Krogstad and Cameron Ball, both first-year graduate students, agreed to pursue the project, at a meeting held last year.




Ball added: "This method allows controlled release of multiple compounds. We were able to tune the fibres to have different release properties."




One of the fabrics dissolves within minutes, offering users immediate protection, while another fabric dissolves gradually over a few days, providing an alternative to the birth-control pill, to provide contraception and protect against HIV.


Chlamydia Damages Sperm, Experts Found

 

chlamydia transmission , which is often known as the silent disease because it has few symptoms, reduces a man's ability to produce children, they found.




 
Research has found Chlamydia damages sperm
 The disease, which is still on the rise in the UK, is more well known for making women infertile if left untreated.




But now researchers, led by Dr Jose Fernandez from Canalejo University Hospital in La Coruna, Spain, have discovered how chlamydia also affects men.




They looked at the damaged sperm of 143 men from infertile couples and compared it with sperm from 50 fertile men.




 




The infertile men had chlamydia and another common urinary tract infection called Mycoplasma.




The level of damage - or DNA fragmentation - in the infertile men's sperm was more than three times higher than in healthy men.




The concentration of their sperm, its ability to swim quickly and defects in the shape of it were also poor when compared with the healthy volunteers.




The experts then treated 95 of the infertile men with antibiotics and found their DNA sperm damage improved an average of 36% after four months.




During that period, 13% of the couples got pregnant and, after the treatment was finished, 86% got pregnant.




The findings were released today at the American Society for Reproductive Medicine conference in Washington DC.




Figures published in July by the Health Protection Agency showed a 4% rise in chlamydia between 2005 and 2006, from 109,418 cases to 113,585.




Experts have been particularly concerned about rates of chlamydia among young people, with the NHS launching a national screening programme.




In 2006/07, 115,073 women under 25 were screened but experts are urging more young men to get tested, with only 31,126 screened during the same period.




Dr Allan Pacey, senior lecturer in andrology at the University of Sheffield and Secretary of the British Fertility Society, said more needed to be done to target the younger generation.




He said: "The message is that we might think of chlamydia as a disease that damages female fertility, but we need to think again.




"It does damage female fertility, but it appears to damage male fertility too.




"The thing that drives most men to sexual health clinics is symptoms, and chlamydia is often symptom-free.




"Chlamydia is getting out of control. We have got to encourage men as well as women to go for screening, but men are more reluctant to do this if they don't have symptoms.




"It is the 18 to 25 age group that is of most concern. There should be a page on Facebook you can log onto and sort screening out."




Dr Fernandez said more research was needed to follow up his study.




And he added: "We've developed a new technique that allows us to look at the extent of DNA fragmentation in sperm cells using a microscope. "The purpose of our work was to analyse if there's an increase in fragmentation of DNA with infection.




"It was found after four months of treatment there was a significant decrease in DNA damage that could improve pregnancy rates in these couples.




"Fertility clinics should check for these infections."


Chlamydia Infection May Pave Way For Cancer Via DNA Damage

std symptoms can cause DNA damage that may increase the risk of later developing cancer, a new study suggests.


In the study, human cells growing in lab dishes that were infected with chlamydia were more likely to have DNA damage compared to cells not infected with chlamydia. What's more, this DNA damage was not always repaired properly by the cell, increasing the chances of genetic mutations.


Normally, cells with such DNA damage would activate a process that kills the cells, so that the cell does not turn cancerous. But in the study, the cells with DNA damage overrode this mechanism, and continued to divide. The continued division of cells with DNA mutations could eventually lead to cancer, the researchers said.


Earlier studies found an association between chlamydia infections and an increased risk of cervical and ovarian cancer in people, but such studies cannot prove cause and effect. The new study provides a biological explanation for how chlamydia could increase the risk of cancer.


However, because the study was conducted in cells in a lab dish, more research is needed to show the same thing occurs in people.


The new study, conducted by researchers at the Max Planck Institute for Infection Biology in Berlin, was published June 12 in the journal Cell Host & Microbe.


Chlamydia is a sexually transmitted disease caused by the bacteria Chlamydia trachomatis. Most infected people have no symptoms, according to the Centers for Disease Control and Prevention. However, untreated infections can damage the reproductive tract in women, and cause infertility. Complications from untreated infections are rare in men, but the condition can cause a burning sensation when urinating, and very rarely, prevent a man from fathering children, the CDC says.


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