sperm motility

Sperm Motility, Testosterone Levels Lower in Active IBD

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Severe active inflammatory bowel disease (IBD) is associated with impaired sperm motility and reduced testosterone levels, according to results from a tertiary IBD center in Denmark.

“Quite surprisingly, only progressive sperm motility and testosterone levels were affected by severe disease flare in patients with inflammatory bowel disease,” Dr. Ann Grosen from Aarhus University Hospital told Reuters Health by email. “We did not see an effect on sperm DNA integrity, sperm concentration, or the morphological appearance of sperm cells during severe disease. Fortunately, both sperm motility and testosterone levels (were) restored after remission in disease was obtained.”

Previous studies have found that men with recent IBD activity are more likely to experience difficulty conceiving than are men in sustained remission. But few studies have investigated the effects of IBD and its treatment on semen quality and sperm DNA integrity.

Dr. Grosen’s team investigated the effects of severe active IBD on semen quality, sperm DNA integrity and the hypothalamic-pituitary-gonadal axis, as well as the effects of infliximab and adalimumab, in 20 men with severe disease, 11 of whom achieved remission on high-dose steroids and nine of whom required additional infliximab therapy to achieve remission.

The team also included 19 outpatients who initiated anti-TNF-alpha therapy and 17 who discontinued anti-TNF-alpha treatment due to sustained remission, for an overall total of 38 men who received infliximab and seven who received adalimumab.

At the time of follow-up, all 20 men with severe disease and all 28 patients who initiated anti-TNF-alpha therapy were in remission and had been for at least three months. They had been treated for a median 5.4 months at the time of follow-up semen sampling.

Among men with severe active disease and those who started anti-TNF-alpha therapy, progressive motility values were abnormally low (mean, 28.4%), based on World Health Organization reference limits, and increased to normal levels (mean, 37.4%) after the patients achieved remission.

All other semen parameters were within the normal range and did not differ significantly between baseline and follow-up samples for any of the three subgroups.

DNA fragmentation index (DFI) decreased from a median 12.8 before initiation of anti-TNF-alpha therapy to a median 10.0 after the start of the anti-TNF-alpha therapy, the researchers reported in the Journal of Crohn’s and Colitis, online November 30.

Sperm DNA integrity did not differ between baseline and follow-up samples for any of the three subgroups, between men with ulcerative colitis and men with Crohn’s disease, or between infliximab- and adalimumab-treated patients.

Plasma testosterone levels were decreased in men with severe disease and in those who started anti-TNF-alpha therapy, but levels normalized after achieving remission.

Infliximab and adalimumab were detected in serum and seminal plasma collected while men were on maintenance treatment but were undetectable in the off-drug semen samples.

“The levels in semen corresponded to 1-2% of serum levels,” Dr. Grosen said. “Consequently, a potential female exposure through the ejaculate is negligible, and barrier methods are not necessary to use for men who are treated with anti-TNF-alpha drugs. This is especially relevant in case the female partner is pregnant.”

“Physicians should inform men with inflammatory bowel disease that we have seen no alarming effects on sperm quality, and pregnancy can be pursued without drug cessation,” she concluded. “Further, patients should not fear adverse effects on fertility despite disease flares.”

Heart-Stopping Arrow Poison Could Be the Key to Male Birth Control

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A non-toxic version of the compound interrupts fertilization in rats

 

Will blue packets replace pink ones soon?

Will blue packets replace pink ones soon?

After decades of research, development of a male birth control may now be one step closer. My colleagues and I are working on a promising lead for a male birth control pill based on ouabain – a plant extract that African warriors and hunters traditionally used as a heart-stopping poison on their arrows.

Hunters want ouabain to be deadly
Hunters want ouabain to be deadly when used on an arrow, but no one wants a fatal contraceptive.

While the birth control pill has been available to women in the United States for nearly six decades – and FDA-approved for contraceptive use since 1960 – an oral contraceptive for men has not yet come to market. The pill has provided women with safe, effective and reversible options for birth control, while options for men have been stuck in a rut.

Today, men have just two choices when it comes to birth control: condoms or a vasectomy. Together, these two methods account for just 30 percent of contraception used, leaving the remaining 70 percent of contraceptive methods to women. An estimated 500,000 American men opt for a vasectomy each year – a small number given the need for contraception. Vasectomy is an invasive procedure to do that’s also difficult and invasive to reverse.

When it comes to birth control options for men, the need is clear. Unplanned pregnancy rates remain high across the globe. It’s time for more options.

Researchers are exploring both hormonal and nonhormonal options for male birth control pills. Current hormonal agents under study involve the sex steroids progestins and testosterone.

While the male hormonal birth control pill option is in clinical human trials and likely closer to market, it has several potential side effects: In addition to potentially causing weight gain and changes in libido, it has the ability to lower the levels of good cholesterol (HDL-C) in men, which could negatively affect the heart health of users. The long-term effects of using hormones for male oral contraception are unknown, and it will likely be decades before this information is available.

Here at the University of Minnesota, my colleagues and I have focused on nonhormonal contraception methods that work by targeting sperm motility – biology-speak for the sperms’ ability to move or swim effectively. Good motility is a necessary condition for fertilizing a female egg.

In collaboration with Gustavo Blanco at the University of Kansas, we’ve homed in on ouabain: a toxic substance produced by two types of African plants. Mammals also produce ouabain in their bodies, though at lower nonlethal levels that scientists think can help control blood pressure. In fact, physicians have used ouabain in very small doses to treat patients with heart arrhythmias or suffering from heart attacks.

 

A cross-section of a cell membrane

A cross-section of a cell membrane shows how pumps made of protein subunits move sodium and potassium ions in and out of the cell. 

 

Researchers know that ouabain disrupts the passage of sodium and potassium ions through cell membranes; it interferes with the proper function of proteins that transport the ions in and out of cells. Some of the ion-transporting protein subunits targeted by ouabain are found in cardiac tissue – its ability to disrupt proper heart function is what makes ouabain a deadly poison. But ouabain also affects another type of transporter subunit called α4, which is found only in sperm cells. This protein is known to be critical in fertility — at least in male mice.

For 10 years, my colleagues and I have been studying ouabain as a potential breakthrough in our quest for a male birth control pill. However, ouabain by itself isn’t an option as a contraceptive because of the risk of heart damage. So we set out to design ouabain analogs – versions of the molecule that are more likely to bind to the α4 protein in sperm than other subunits in heart tissue.

In the lab, we used the techniques of medicinal chemistry to create a derivative of ouabain that is good at zeroing in on the α4 transporter in sperm cells in rats. Once bound to those cells, it interferes with the sperms’ ability to swim – essential to its role in fertilizing an egg. Our new compound showed no toxicity in rats.

Because the α4 transporter is found only on mature sperm cells, the contraceptive effect should be reversible – sperm cells produced after stopping the treatment presumably won’t be affected. Ouabain may also offer men a birth control pill option with fewer systemic side effects than hormonal options.

Our results are promising because our candidate molecule, unlike ouabain, is nontoxic in rats. Our modification is a big step forward in the process of developing a nonhormonal male birth control pill. But there’s a lot left to do before men can buy this contraceptive at the pharmacy.

After our ouabain analog showed promise in rat studies at reducing sperm motility, future studies will focus on the effectiveness of our lead compound as an actual contraceptive in animals. We need to prove that a reduction in sperm movement translates into a drop in egg fertilization.

Then, we’ll begin the standard steps in drug discovery such as toxicology and safety pharmacology studies as we advance toward planning and conducting clinical trials. Our team is already taking the next step to test our compound in animal mating trials. If things continue as planned, we hope to get to human clinical trials within five years.

Reversible, effective male birth control is within sight. World Health Organization numbers suggest that reducing sperm motility by 50 percent or less is sufficient to temporarily make a man infertile. Our ongoing research brings us one step closer to expanding the options for male birth control, providing the world’s 7.6 billion people with a much-needed option for safe and reversible contraception.

Chemicals found in common household products may affect human sperm.

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In 1991 a study showed that human sperm counts had fallen by almost 50 percent in less than 50 years, which increased the cases of male infertility due to lower sperm count.

Toothpaste and sunscreen could be two of the reasons why male infertility is on the rise.

Sebastian_Tomus_sperm_shutterstock
A few years later researchers discovered that common chemicals used in everyday day items such as soap and toothpaste have a negative effect in the male reproductive system – and a new study has found a way of testing the impact of household products on human sperm.
Some chemical substances mimic either male sex hormones or female sex hormones and both interfere with the male reproductive system by slowing down sperm, explains Steve Connor over at the Independent.
The chemicals commonly found in detergents, plastics, toothpaste and even sunscreen also make sperm release enzymes needed to fertilise the egg cell before it reaches it, which may also be a cause of infertility.
In their study the researchers found that these chemicals have what Connor describes as a “cocktail effect”, meaning the presence of one amplifies the effects of others.
“For the first time, we have shown a direct link between exposure to endocrine-disrupting chemicals from industrial products and adverse effects on human sperm function,” said Professor Niels Skakkebaek, of Copenhagen University Hospital in Denmark, to the Independent.
A report from the Centre of Advanced European Studies and Research found that out of 96 common household chemicals, a third had an effect on the protein that controls sperm motility and swimming agility.
“In my opinion, our findings are clearly a concern as some endocrine-disrupting chemicals are possibly more dangerous than previously thought,” said Skkakkebaek. “However, it remains to be seen from forthcoming clinical studies whether our findings may explain reduced couple fertility which is very common in modern society.”
This study is the first one that highlights how common lifestyle or environmental changes affect male fertility.