Study findings could lead to new clinical laboratory testing biomarkers designed to assess for male infertility
Clinical laboratories are increasingly performing tests that have as their biomarkers the DNA and enzymes found in human microbiota. And microbiologists and epidemiologists know that like other environments within the human body, semen has its own microbiome. Now, a study conducted at the University of California, Los Angeles (UCLA) has found that the health of semen microbiome may be linked to male infertility.
The UCLA researchers discovered a small group of microorganisms within semen that may impair the sperm’s motility (its ability to swim) and affect fertility.
A total of 73 individuals were included in the study. About half of the subjects were fertile and already had children, while the remaining men were under consultation for fertility issues.
“These are people who have been trying to get pregnant with their partner, and they’ve been unsuccessful,” Sriram Eleswarapu, MD, PhD, a urologist at UCLA and co-author of the study, told Scientific American. “This latter group’s semen samples had a lower sperm count or motility, both of which can contribute to infertility.”
“There is much more to explore regarding the microbiome and its connection to male infertility,” said Vadim Osadchiy, MD (above), a resident in the Department of Urology at UCLA and lead author of the study, in a UCLA news release. “However, these findings provide valuable insights that can lead us in the right direction for a deeper understanding of this correlation.” Might it also lead to new biomarkers for clinical laboratory testing for male infertility? (Photo copyright: UCLA.)
Genetic Sequencing Used to Identify Bacteria in Semen Microbiome
Most of the microbes present in the semen microbiome originate in the glands of the male upper reproductive tract, including the testes, seminal vesicles and prostate, and contribute various components to semen. “Drifter” bacteria that comes from urine and the urethra can also accumulate in the fluid during ejaculation. Microbes from an individual’s blood, or his partner’s, may also aggregate in semen. It is unknown how these bacteria might affect health.
“I would assume that there are bacteria that are net beneficial, that maybe secrete certain kinds of cytokines or chemicals that improve the fertility milieu for a person, and then there are likely many that have negative side effects,” Eleswarapu told Scientific American.
The scientists used genetic sequencing to identify different bacteria species present within the semen microbiome. They found five species that were common among all the study participants. But men with more of the microbe Lactobacillus iners (L. iners) were likelier to have impaired sperm motility and experience fertility issues.
This discovery was of special interest to the team because L. iners is commonly found in the vaginal microbiome. In females, high levels of L. iners are associated with bacterial vaginosis and have been linked to infertility in women. This is the first study that found a negative association between L. iners and male fertility.
The researchers plan to investigate specific molecules and proteins contained in the bacteria to find out whether they slow down sperm in a clinical laboratory situation.
“If we can identify how they exert that influence, then we have some drug targets,” Eleswarapu noted.
Targeting Bacteria That Cause Infertility
The team also discovered that three types of bacteria found in the Pseudomonas genus were present in patients who had both normal and abnormal sperm concentrations. Patients with abnormal sperm concentrations had more Pseudomonas fluorescens and Pseudomonas stutzeri and less Pseudomonas putida in their samples.
According to the federal National Institute of Child Health and Human Development (NICHD), “one-third of infertility cases are caused by male reproductive issues, one-third by female reproductive issues, and the remaining one-third by both male and female reproductive issues or unknown factors.” Thus, learning more about how the semen microbiome may be involved in infertility could aid in the development of drugs that target specific bacteria.
“Our research aligns with evidence from smaller studies and will pave the way for future, more comprehensive investigations to unravel the complex relationship between the semen microbiome and fertility,” said urologist Vadim Osadchiy, MD, a resident in the Department of Urology at UCLA and lead author of the study, in a UCLA news release.
More research is needed. For example, it’s unclear if there are any links between the health of semen microbiome and other microbiomes that exist in the body, such as the gut microbiome, that cause infertility. Nevertheless, this research could lead to new biomarkers for clinical laboratory testing to help couples who are experiencing fertility issues.
Dogs’ acute sense of smell can even surpass effectiveness of some clinical laboratory testing in detecting certain diseases in humans
When it comes to COVID-19 testing, a recent Italian study demonstrates that trained dogs can detect SARS-CoV-2 with accuracy comparable to rapid molecular tests used in clinical laboratories. The researchers wanted to determine if dogs could be more effective at screening people for COVID-19 at airports, schools, and other high-traffic environments as a way to detect the coronavirus and reduce the spread of this infectious disease.
Scientists at the State University of Milan in Italy conducted a study that shows dogs can be trained to accurately identify the presence of the COVID-19 infection from both biological samples and by simply smelling an individual.
For their validation study, the Italian team trained three dogs named Nala, Otto, and Helix, “to detect the presence of SARS-CoV-2 in sweat samples from infected people. At the end of the training, the dogs achieved an average sensitivity of 93% and a specificity of 99%, showing a level of accuracy highly consistent with that of the RT-PCR [reverse transcription polymerase chain reaction] used in molecular tests and a moderate to strong reproducibility over time,” Nature reported.
RT-PCR tests are the current gold-standard for SARS-CoV-2 detection. This is yet another example of scientists training dogs to smell a disease with “acceptable” accuracy. This time for COVID-19.
“We only recruited dogs that showed themselves predisposed and positively motivated to carry out this type of activity. One of the fundamental aspects was not to cause stress or anxiety in the subjects used,” Federica Pirrone, PhD (above), Associate Professor, Department of Veterinary Medicine and Animal Sciences, University of Milan, and one of the authors of the study told Lifegate. “Training always takes place using positive reinforcement of a food nature: whether it’s a particularly appetizing morsel, a biscuit, or something that associates the dog’s search with a rewarding prize.” In some instances, dogs have been shown to be as good or more effective at detecting certain diseases than clinical laboratory testing. (Photo copyright: Facebook.)
Dogs More Accurate than Rapid Antigen Testing
Nala and four other dogs (Nim, Hope, Iris and Chaos) were later trained by canine technicians from Medical Detection Dogs Italy (MDDI) to identify the existence of the SARS-CoV-2 virus by directly smelling people waiting in line in pharmacies to get a nasal swab to test for the coronavirus.
Working with their handlers, the five dogs accurately signaled the presence or absence of the virus with 89% sensitivity and 95% specificity. That rate is “well above the minimum required by the WHO [World Health Organization] for rapid swabs for SARS-CoV-2,” according to Nature.
“The results of studies published so far on the accuracy of canine smell in detecting the presence of SARS-CoV-2 in biological samples (e.g., saliva, sweat, urine, trachea-bronchial secretions) from infected people suggest that sniffer dogs might reach percentages of sensitivity and specificity comparable to, or perhaps even higher, than those of RT-PCR,” the scientists wrote in Scientific Reports.
“However, although most of these studies are of good quality, none of them provided scientific validation of canine scent detection, despite this being an important requirement in the chemical analysis practice. Therefore, further applied research in this field is absolutely justified to provide definitive validation of this biodetection method,” the researchers concluded.
Other Studies into Using Dogs for Detecting Disease
Scientists from the Division of Biological and Health Sciences, Department of Agriculture and Livestock at the University of Sonora; and the Canine Training Center Obi-K19, both in Hermosillo, Mexico, conducted the study “as part of a Frontiers of Science Project of the National Council of Science and Technology (CONACYT), in which in addition to analyzing sweat compounds, trained dogs are put to sniff the samples and make detections in people who show symptoms or could be positive for coronavirus,” Mexico Daily Post reported.
The researchers trained four dogs with sweat samples and three dogs with saliva samples of COVID-19 positive patients. The samples were obtained from a health center located in Hermosillo, Sonora, in Mexico. The dogs were restricted to spend five minutes per patient and the researchers calculated the performance of the dogs by measuring sensitivity, specificity, and their 95% confidence intervals (CI).
The researchers concluded that all four of the dogs could detect COVID-19 from either sweat or saliva samples “with sensitivity and specificity rates significantly different from random [sampling] in the field.” According to the Frontiers in Medicine study, the researchers found their results promising because, they said, it is reasonable to expect the detection rate would improve with longer exposure to the samples.
The objective of the Mexican researchers is for the dogs to ultimately reach the sensitivity range requested by WHO for the performance of an antigen test, which is at least 80% sensitivity and 97% specificity. If that goal is achieved, dogs could become important partners in the control of the COVID-19 pandemic, the scientists wrote.
Data obtained so far from these studies indicate that biosensing dogs may represent an effective method of screening for COVID-19 as well as other diseases. More studies and clinical trials are needed before the widespread use of dogs might become feasible. Nevertheless, scientists all over the world are finding that Man’s best friend can be a powerful ally in the fight against the spread of deadly diseases.
In the meantime, the gold standard in COVID-19 testing will continue to be the FDA-cleared assays used by clinical laboratories throughout the United States.
It’s the latest example of how genetic technologies have advanced to the point where DNA can be extracted and sequenced from human remains that are thousands of years old, often generating new insights that can benefit clinical laboratory testing
How might an individual in Pompeii who died in the famous Mount Vesuvius volcanic eruption of 79 AD help medical science today? The answer is that sequencing this individual’s DNA may yield insights into health conditions and infectious diseases of that era that could help scientists better understand disease today in ways that improve diagnosis and clinical laboratory testing.
Additionally, researchers studying genetic sequencing are discovering the technology has many more capabilities that previously thought. One such example involves scientists from the University of Copenhagen, the University of Salento, and victims of the eruption. This research team has determined that even severely damaged biological samples may contain viable DNA.
When Mount Vesuvius erupted, volcanic ash and pumice buried many residents of the town of Pompeii in southern Italy. The ash was estimated to have been about 500 degrees Fahrenheit, which should have been hot enough to cause significant damage to DNA. However, it appears the pyroclastic materials released during the eruption may instead have preserved some of the victims’ DNA.
“One of the main drivers of DNA degradation is oxygen (the other being water),” Gabriele Scorrano, PhD, Assistant Professor, University of Copenhagen and lead author of the study told CNN. “Temperature works more as a catalyst, speeding up the process. Therefore, if low oxygen is present, there is a limit of how much DNA degradation can take place.”
The scientists succeeded in performing completed genetic sequencing on one of the victims of the violent eruption. This has genetic researchers rethinking how DNA could be recovered from damaged biological materials.
“In the future, many more genomes from Pompeii can be studied,” anthropologist Serena Viva, PhD (above), a postdoctoral researcher at the University of Salento in Italy and one of the authors of the study told the Guardian. “The victims of Pompeii experienced a natural catastrophe, a thermal shock, and it was not known that you could preserve their genetic material. This study provides this confirmation, and that new technology on genetic analysis allows us to sequence genomes also on damaged material.” What new clinical laboratory testing may come out of this study is not known. But it shows that there is still much to learn about genetic sequencing. (Photo copyright: University of Salento.)
Findings Suggest High Levels of Genetic Diversity
“There was the expectation that the high temperatures would make our effort in DNA sequencing in Pompeii fruitless,” Scorrano stated. “Cremated bodies, for example, show no sign of DNA preservation according to multiple studies.”
The scientists examined the skeletal remains of two victims found in a building known as Casa del Fabbro or House of the Craftsman to determine if any DNA was present. One skeleton was that of a man in his 30’s who was about five feet four inches in height and the other skeleton was of a woman who appeared to be at least 50 years of age and around five feet tall.
Although the researchers did obtain genetic material from both skeletons, they were only able to sequence the entire genome from the remains of the male skeleton.
The researchers compared his DNA with that of 1,030 other ancient and 471 modern western Eurasian people. The results suggest that the DNA from the male Pompeii skeleton shares the most similarities with people who currently live or lived in central Italy in the past.
Further analysis of the man’s DNA identified groups of genes that are commonly found in people from the island of Sardinia, but not in other people who lived in Italy during the Roman Imperial age. This suggested to the researchers that there may have been high levels of genetic diversity across Italy in 79 AD when Mount Vesuvius erupted.
Additional testing also identified sequences that are commonly found in a group of bacteria known to cause tuberculosis of the spine (Pott disease), a common ailment at that time. This implies the man had the illness when he perished.
The photo above shows the two skeletons (one man and one woman) found in Pompeii’s Casa del Fabbro. Though the University scientists tried to extract full sequences from both skeletons, they only succeeded with the male. (Photo copyright: Notizie degli Scavi di Antichità, 1934, p. 286, fig. 10.)
First Pompeiian Genetic Sequence
Scientists had attempted to sequence DNA from Pompeiian victims before, but previous endeavors to analyze more than small DNA strands failed.
“To our knowledge, our results represent the first successfully sequenced Pompeiian human genome,” they wrote in Nature Scientific Reports. “Our initial findings provide a foundation to promote an intensive and extensive paleogenetic analysis in order to reconstruct the genetic history of population from Pompeii, a unique archaeological site.”
It is unclear how equivalent studies could fare in the future, but the researchers involved in this study hope to use their sequencing techniques on other remains. It is possible that DNA from this Roman man who died in Pompeii in 79 AD may be used to determine if he has any descendants living today.
After months of research and the charting of Cheddar Man’s DNA, the scientists visited a school in Cheddar to extract DNA samples from schoolchildren and look for DNA matches. About 20 samples were taken in total including one from a teacher named Adrian Targett.
“They wanted to take DNA samples from some of the students whose families had lived longest in the area,” Targett told the Los Angeles Times. “I gave a [cheek swab] sample too, just to encourage the children and to make up the numbers.”
Although none of the children were a genetic match to the Cheddar Man, Targett was identified as a direct descendant of the skeleton.
“It’s a bit frightening to think that there are all those links across all those generations,” Targett said. “But the nice thing is that there are links that are so strong. We are all descended from an ancestor like Cheddar Man. Who knows how many people we are related to and don’t know about?”
The Pompeii DNA research is the latest example of how the ongoing reduction in the cost, faster throughput, and increased accuracy of genetic sequencing is allowing scientists to gain new knowledge from ancient artifacts. In turn, some of these new insights may lead to improving how certain health conditions are diagnosed, possibly using novel clinical laboratory tests developed as a result of this research.
Clinical laboratory assays on a USB stick could become a powerful tool in the treatment and containment of HIV-1 in low-resource regions, such as sub-Saharan Africa
Imagine a small USB device that plugs into a computer and, using a small sample of blood, is capable of detecting the presence of HIV and measuring its viral load in that individual. Such technology exists and was created by a team of scientists in the United Kingdom (UK). However, it is not yet ready for use by clinical laboratories.
A story published on the mobile technology news blog Quartz pointed out that more than 24-million of the 37-million people worldwide infected with HIV live in sub-Saharan Africa. It is widely recognized that high cost and lack of access to medical care and clinical laboratory services remain a barrier to diagnosis, treatment, and containment of the disease. “[I]mproving diagnostics is now a key part of global strategies to combat [HIV],” wrote the study authors in a paper published in Nature Research journal Scientific Reports. (more…)
