Infertility Cured In Mice; Are Human Males Next?

Male infertility may soon be a thing of the past according to mice. This week new research has been released that Japanese scientists have used laboratory-made sperm, using embryonic cells, to restore fertility in sterile mice. This may open up new avenues for researching and treating infertility in people. For example, men may be able to reprogram cells from the skin to act like sperm producing entities. Read on for details.

Historically, researchers have tried for years to make sperm and eggs in a dish, with limited success and some controversy. In 2003, several groups of scientists showed that it was possible to transform mouse embryonic stem cells into both sperm and eggs, but pregnancy failed.

In 2006 another team used lab-grown sperm to produce six mice, but the animals suffered genetic abnormalities and all died early and in 2009, researchers at Newcastle University made headlines by reporting the creation of human sperm in a test tube. Their paper was retracted weeks later on charges of plagiarism.

Now, the researchers added growth factors and other chemicals that are known to control activities such as cell proliferation and differentiation to mouse embryonic stem cells which had the effect of turning the embryonic cells into epiblast-like cells in a lab dish. These cell types are deposited early in embryogenesis in developing organs and persist in several organs into adulthood.

Next, by replicating the signaling process learned from the 2009 experiment, they coaxed the epiblast-like cells to become primordial germ cells. These primitive germ cells were transplanted into the testes of 7-day-old mice that were sterile and therefore couldn't produce sperm naturally. But they now produced normal-looking sperm. Quite the breakthrough.

The lab-made sperm were used to fertilize eggs in a dish, creating 214 embryos, each comprising two cells. The embryos were transplanted into several female mice, which gave birth to a total of 65 healthy male and female pups.

Dr. Saitou, the research team leader stated:

"The mouse babies are just fine and they've had normal, fertile babies of their own. The pregnancy rate achieved in the mice was comparable to what's typically seen using naturally produced sperm and artificial insemination."

Now this exact process can't be identically replicated in adult male humans, but it may be possible to reprogram a man's mature cells into an embryonic-like state, and coax those cells to become healthy sperm in a dish.

The Japanese scientists did just that. They got reprogrammed mouse cells to turn into lab-made sperm, and then used the sperm to fertilize eggs and produce babies in the mice.

The ability to reprogram cells into an embryonic-like state is one of the most exciting advances in biology. But it is still an unreliable technique since it often requires the use of viruses that can trigger tumors. Not surprisingly, the Kyoto scientists found that 20% of the baby mice produced via reprogramming died prematurely, some from tumors.

George Daley, director of the stem-cell transplantation program at Children's Hospital Boston commented:

"It's a brilliant set of experiments. They restored fertility in the mice. It lays the groundwork for major insights into sperm development and fertility. It would be a monumental achievement since there's currently no method for restoring female fertility."

SOURCE:MEDICALNEWSTODAY

Male Fertility May Be Affected By Cell Phone Use

Men who have been diagnosed with poor sperm quality and who are trying to have children should limit their cell phone use. Researchers have found that while cell phone use appears to increase the level of testosterone circulating in the body, it may also lead to low sperm quality and a decrease in fertility.

"Our findings were a little bit puzzling," says Rany Shamloul, a postdoctoral fellow in the Department of Pharmacology and Toxicology and lead researcher on the project. "We were expecting to find different results, but the results we did find suggest that there could be some intriguing mechanisms at work."

The research team discovered that men who reported cell phone use had higher levels of circulating testosterone but they also had lower levels of luteinizing hormone (LH), an important reproductive hormone that is secreted by the pituitary gland in the brain.

The researchers hypothesize that electromagnetic waves (EMW) emitted by cell phones may have a dual action on male hormone levels and fertility. EMW may increase the number of cells in the testes that produce testosterone; however, by lowering the levels of LH excreted by the pituitary gland, EMW may also block the conversion of this basic circulating type of testosterone to the more active, potent form of testosterone associated with sperm production and fertility.

More in-depth research is needed to determine the exact ways in which EMW affects male fertility.

Source:
Christina Archibald
Queen's University

Laptops Can Seriously Affect A Man's Sperm Quality

Males who use laptops on their laps are likely to experience scrotal hyperthermia - elevated temperatures in their testicles - which can significantly affect the quality of their sperm, and consequently their fertility, US scientists report in the medical journal Fertility and Sterility. The authors add that even if they protect their laps with a lap pad, scrotal hyperthermia still occurs. The only way a male can be sure to protect his fertility when using a laptop is by placing it on a desk, using it with legs apart while using a lap pad for no longer than 28 minutes, or using the laptop on his lap with knees together for very short periods.

Yelim Sheynkin, M.D. (urologist) and team from the State University of New York at Stony Brook set out to evaluate how to prevent scrotal hyperthermia among male laptop users. Their study involved 29 health male volunteers.

The scientists measured the temperatures of the left and right side of the scrotum, as well as the laptop and lap pad during three separate 60-minute sessions - all the participants were using a laptop in the following ways:

· Sitting with their knees together (approximated legs) and the laptop on their laps

· Sitting with their knees together, laptop on lap, and with lap pad between their laptops and their laps

· Sitting with their legs apart at a 70° angle, laptop on lap, and with lap pad between their laptops and their laps

Their goal was to measure any rise in scrotal temperatures.

The authors wrote that scrotal temperatures went up considerably, in spite of the position of their legs and whether or not they used a lap pad.

Scrotal temperature did go up less and the rise occurred later when the men had their legs apart at a 70° angle. However, even then, the rise in scrotal temperature was cause for concern.

Below are some of the highlighted results:

· Knees together, laptop on lap (no lap pad)
Scrotal temperature rise - left side from 0.96C to 2.31C, right side from 0.91C to 2.56C.
The scrotum started rising in temperature within 11 minutes.

· Knees together, laptop on lap, using lap pad
Scrotal temperature rise - left side from 0.69C to 2.18C, right side from 0.72C to 2.06C.
The scrotum started rising in temperature within 14 minutes.

· Legs apart, laptop on lap, using lap pad
Scrotal temperature rise - left side from 0.66C to 1.41C, right side from 0.62C to 1.47C.
The scrotum started rising in temperature within 28 minutes.

The authors wrote in conclusion:

Sitting position with closely approximated legs is the major cause of scrotal hyperthermia. Scrotal shielding with a lap pad does not protect from scrotal temperature elevation. Prevention of scrotal hyperthermia in LC users presently is not feasible. However, scrotal hyperthermia may be reduced by a modified sitting position (legs apart) and significantly shorter use of LC.

Antioxidants May Improve Male Fertility

Couples who struggle to conceive could find baby-making help from antioxidants such as vitamin E and zinc, hints a new review of more than 30 studies.

The researchers focused on men who were subfertile — less fertile than average but still capable of making a baby — and found that those who took antioxidants were more than four times as likely to get their partners pregnant than subfertile men who did not take the supplements.

The New Zealand team stops short of saying that antioxidants actually improve fertility, however. More research is needed to be sure.

Subfertility affects one in 20 men and is responsible for half of delayed conceptions. Up to 80 percent of cases are thought to be due to the effects of oxidative stress on sperm cells, lowering both their numbers and their quality.

Oxidative stress happens when molecules known as free radicals, byproducts of cell metabolism, damage DNA and cells' ability to function. Antioxidants, including certain vitamins and nutrients, help to protect cells by stabilizing free radicals.

This has led some experts to wonder if antioxidants might help sperm stay swimmingly healthy.

"Oral supplementation with antioxidants may go some way to improve a couple's chance of conception," lead researcher Marian Showell of the University of Auckland, in New Zealand, told Reuters Health in an e-mail.

To see if the research to date backs up that idea, Showell and her colleagues reviewed 34 studies that involved nearly 3,000 couples undergoing fertility treatments, including in vitro fertilization and intrauterine insemination — two of the most commonly used methods of boosting conception odds when sperm-related issues are involved. Each study investigated the potential role of one or more antioxidants.

Based on 96 pregnancies among 964 couples in 15 of the studies, the researchers found that antioxidant use by the male partner increased the odds of conception four-fold.

Further, men taking antioxidants improved the likelihood of their partners giving birth to a live baby by a factor of five, the researchers report in The Cochrane Library. Only three of the studies contained data on live births, however.

"The findings of increased live birth rates with antioxidants are based on a total of only 20 births — a relatively small number," Dr. Mark Sigman of Brown University, in Providence, R.I., who was not involved in the review, told Reuters Health in an e-mail.

Sigman, whose research found no improvement in semen quality with the antioxidant carnitine, was cautious about making too much of the review's results.

The included studies did not use the same types or numbers of antioxidants, he added. As a result, the researchers could not determine the effectiveness of individual supplements.

In addition to oral supplements, antioxidants can be found in a range of foods, from cranberries to collard greens, tomatoes and mozzarella cheese.

Both Sigman and Showell cautioned that couples should not count on antioxidants to overcome their fertility challenges. Even if certain supplements prove effective, further research is needed to determine which couples could reap the specific benefits.

"It is unrealistic to think one treatment will be good for most couples," noted Sigman.
"There is no evidence that antioxidants cause harm," he added. "But since we also don't know which antioxidants or doses are beneficial, and none have FDA approval for infertility — consumers are left with purchasing these based on very limited data."

SOURCE: fertilityauthority.com

STUDY FINDS GENE LINKED TO MALE INFERTILITY

A study has shown that mutations in the NR5A1 gene may be responsible for many unexplained cases of male infertility.
The research team, led by scientists from the Pasteur Institute in Paris and Institute of Child Health in London, screened a group of 315 men who were unable to produce sperm, for mutations in the gene NR5A1.
The gene encodes for a protein that has a critical role in the development of the reproductive organs and in reproduction, and has previously been linked to problems with sexual development in both men and women.
The researchers found that seven of the effected individuals had mutations in this gene, while no mutations were found in a control group of 729 men who had normal sperm production.
Four of these men were also found to have altered levels of sex hormones, and another had testicular abnormalities, suggesting a link between the mutations and the problems with sperm production.
The study, published in the American Journal of Human Genetics, represents an important step in the search for genes that may be responsible for male infertility, which accounts for 30 to 50 percent of the fertility problems faced by couples trying to conceive.
The authors told the BBC: 'Approximately four percent of men with otherwise unexplained failure to produce sperm carry mutations in the NR5A1 gene'.
To date only a small number of genes have been linked to male infertility, with the majority of sperm production problems having no obvious cause.
Dr Allan Pacey, a fertility expert from Sheffield University said: 'Although this gene defect affects only a small number of men, we need more studies like this so we can fill in the gaps in

SOURCE: BIONEWS.ORG

Cola lowers sperm count, study shows

If you're trying to have a baby, it might be a good idea to keep an eye on your partner's cola intake, as a Danish researchers have found that big cola drinkers can have sperm counts up to 30 percent lower than normal.

Researchers at Rigshospitalet, Copenhagen University Hospital, were looking for a link between caffeine and male fertility but found lower sperm counts were not the result of the caffeine in cola, as was previously thought, PhysOrg.com reported.

The researchers studied sperm samples taken from 2554 young men during their physical examinations for Danish military service between 2001 and 2005. The men were also surveyed regarding their intake of caffeine from various sources, including cola, and asked questions about their lifestyle and diet.

Results showed that those with low to moderate total caffeine intake and cola consumption (up to 800mg per day caffeine and up to 14 500ml bottles of cola per week) didn't display any lowering of sperm count. But those with a high intake of caffeine and cola (more than 800mg per day and more than 14 500ml bottles a week) did show a lower sperm count, although the figure was only significant for those who drank a lot of cola.

The 93 men who drank a litre or more of cola a day displayed a much lower count.

Reliable Home Male Fertility Test? Accurate Sperm Counts Now Possible

A new 'fertility chip', developed by researchers at the University of Twente's MESA+ Institute for Nanotechnology, can accurately count spermatozoa in sperm. This is an important step towards the development of a compact device for reliable 'pre-scanning' of male fertility.

The researchers are publishing the invention of the chip in the scientific journal Lab on a Chip.

Every year more than 10,000 couples in the Netherlands apply for help because of involuntary childlessness. A sperm analysis is typically the first step of fertility research. Testing sperm quality requires stringent pre-test preparations and a specialized laboratory. Tests often have to be repeated two to five times for sufficient reliability. If men can carry out the tests in the privacy of their own home this makes the procedure much less awkward for them. Moreover, the probability of a reliable diagnosis is increased as well. Finally, the researchers think that the costs for health insurers can be decreased too.

Sperm counts

The chip developed by researcher Loes Segerink can accurately count spermatozoa. Concentration is an important indication of the sperm count: the norm for fertility is 20 million spermatozoa per millilitre of ejaculate. Simple home tests are available, but these can only indicate that the sperm count is 'above or below the norm'. These tests are too limited because they do not actually measure the concentration of spermatozoa.

On the new chip, the spermatozoa flow through a fluid channel, above which electrodes are fitted. When a cell flows under this 'bridge', its electrical resistance changes momentarily, and this event is counted. It is important that the count distinguishes between spermatozoa and other particles or cells in the fluid: if other particles are included the count will be unreliable. Segerink added minuscule balls to the fluid to test its selectivity. The method proved to be selective enough to distinguish between the balls and the spermatozoa. White blood cells were also distinguished by the chip. The number of white blood cells tells us something about sperm quality and so this is important additional information for the gynaecologist.

Activity and shape

Concentration is not the only indicator of sperm quality. Spontaneous activity -- also known as motility -- and the shape of the spermatozoa are also important factors. Further research will need to establish whether these two quality characteristics can be measured in a similar manner, so that a compact device can be developed in which a chip can be inserted for single use. The user will only be able to see that the test has been completed successfully; the gynaecologist will inform him of the actual results personally.

Loes Segerink developed the 'fertility chip' in Prof. Albert van den Berg's BIOS Lab-on-a-Chip research group. This group is part of the University of Twente's MESA+ Institute for Nanotechnology. The research is financed by Technology Foundation STW.

The publication 'On-chip determination of spermatozoa concentration using electrical impedance measurements' by Loes Segerink, Ad Sprenkels, Paul ter Braak, Istvan Vermes and Albert van den Berg, has been published online in the form of an Advance Publication, and will appear in the scientific journal Lab on a Chip in the near future.

SOURCE:SCIENCEDAILY