Turek On Men's Health » genetics

It Takes Two to Tango

Paul Turek, MD — Mon, 30 Apr 2012 15:00:32 +0000

The genetic dance: adding spice to life.

The Case of the Month is an actual patient from The Turek Clinic. It is presented to highlight Infertility Awareness Week.

The Dance Begins

He is a 36-year old who has been trying to conceive with his 35-year old wife for 2 years. After 5 months of trying, the couple achieved a pregnancy she miscarried at 8 weeks. After trying for another 7 months, they conceived again and again lost the baby, this time at 9 weeks. The couple appears disheartened and broken as they tell the story in the office.

“I’m not sure what’s wrong with me…I can’t seem to carry a baby,” says the wife in tears. “My tests look great but for some reason, nothing lasts!” she continues. The husband then pipes in: “We checked on me after the first miscarriage and my sperm count was low. Could I be the problem?” Great question.

The Pregnancy Dance

Normally, the human sperm and egg meet in the fallopian tube soon after sex. Then, over the next several days, a highly orchestrated genetic dance begins. Within 2 days, the sperm molecularly “undresses” for the egg, revealing, in full nakedness, its genetic material. Inspecting the male genome, the egg surveys and corrects its imperfections, making it whole and usable. Based on how this dance goes, usually before day 3, the egg (now an 8 cell embryo) is compelled to make an executive decision: continue developing or stop the dance. This decision is probably the first of many quality control decisions the embryo makes as it develops and is highly dependent upon the acceptability of the sperm genome.

Sperm as Dance Partners

Can sperm contribute to early miscarriages? Yes they can.

And this is despite the fact that you may never see this on any list of presumed causes of pregnancy loss. Here are the ways in which this is thought to happen:

Imbalanced Sperm Chromosomes. The classic example is when chunks of genetic material are misplaced within sperm chromosomes. Termed Robertsonian translocations, imbalanced sperm chromosomes can be found in perfectly healthy men and packaged into perfectly healthy looking (e.g. morphologically normal) sperm. The only clue may be that the sperm concentration in the ejaculate is low (termed oligospermia). When the egg and sperm genomes marry after fertilization, embryonic development is affected by the abnormal chromosomal balance in sperm, and the dance ends when the partners trip over each other’s feet. Fortunately, a blood test termed a karyotype can detect this in a man’s blood and preimplantation genetic diagnosis can be used with assisted reproduction to select for normally balanced embryos that lead to successful pregnancies.

Sperm DNA Breaks. More subtle issues with sperm can also lead to miscarriages. While the genetic payload is being prepared and packed for shipping in each sperm well before ejaculation, there may be subtle alternations in packaging quality that allow for breakages to occur in the sperm DNA ladder. Termed sperm DNA fragmentation, this problem is also found in perfectly normal looking sperm at normal sperm concentrations and motilities. Ultimately, in the first few days of embryonic life, the egg in all of its wisdom may be unable to repair the breaks and fragments of sperm DNA and elects to stop developing. And the dance ends.

Unlike with chromosomal issues, poor DNA integrity can result from acquired rather than genetic causes. Such lifestyle factors include such as smoking, fevers, hot baths, illness, infections, medications (anti-depressants and Propecia), chemotherapy, radiation therapy, oxidant exposure (e.g. air pollution, solvents), older paternal age and the good ole’ varicocele, that bag of veins located above the testicle that overheats the factory through abnormal blood drainage pattern. Sperm DNA damage is also measurable through specialized sperm-based assays that detect DNA strand breaks. And unlike chromosomal issues, they may be correctable by lifestyle changes, improved health or by repairing anatomical issues (varicocele).

So, think of chromosomal imbalances as men with two left feet and fragmented sperm DNA as men with shoes on the wrong feet. Either way, the dance just isn’t as smooth as it should be and it just stops in its tracks.

Antibodies and Epigenetics. Of course, there may be other ways that sperm contribute to miscarriage. Men are generally “allergic” to their sperm and some may develop antibodies to their sperm as a result. What is not clear is whether these antibodies induce a reaction from the female host to “attack” the embryo containing these same male allergic proteins. Additionally, the way sperm DNA is “fingerprinted,” termed epigenetics, may also influence pregnancy progression although this science is still in its infancy.

Men and Miscarriages: How Can They Help?

So, sperm matter when it comes to miscarriage. Because of this, my advice is:

See a men’s reproductive specialist if you’re having trouble with miscarriages. A good history and a simple physical exam can assess possible risk factors and lead to lifestyle changes.
Take great care of yourself. Stay healthy, avoid tobacco, exposure to smelly solvents, medications (when possible) and hot tubs and eat a diet rich in antioxidants.
If you’re stuck with airport food, consider taking antioxidants vitamins such as that found in a good male pre-natal supplement.
Similar to advice endlessly given to women, it may help to start when you’re young.

And when the tango begins, please be reminded of the power of the female egg: “Remember, Ginger Rogers did everything Fred Astaire did, but backwards and in high heels.” (Faith Whittlesey)

A Year Without Answers II

Paul Turek, MD — Mon, 19 Mar 2012 15:00:18 +0000

Rug design courtesy of Rex Ray, San Francisco

This is the second of two guest posts from a patient who lives in Europe. He recently recontacted me about his experience with male infertility and how it affected him. Moved by his story and by his emotional fortitude, I asked him if he could share his remarkable journey with others. The first post is from March 12th.

I had to face the fact that I was my own worst enemy. This was an epiphany for me. By becoming a negative person, spontaneity and creativity had left me, high and dry. And gone with it was the ability to problem solve. For me, once of the hardest things that I have ever had to do in my life was to admit that I was the root of the problem, that I was responsible. The epiphany was that because I was the problem, I could also be the agent of change. I could own this. The rebuilding of me had to start with me.

It was at that point that I reached out to a psychiatrist, Our talks helped me find my way back. Honestly, I never knew that these sides of my character even existed, and was even less aware that they would belch from my soul as they did. These sessions allowed me to vent my feelings and, over time, I felt better and better. It felt like I could take the 800-pound gorilla to the doctor’s office and leave it there. And, funny enough, the “gorilla” began shrinking in size with each session, almost to the point of becoming a small, friendly monkey. And although even cute little monkeys can be annoying, these sessions helped me enormously by providing tools and methods to help me better understand, accept and manage such strong feelings.

Modern societies of any culture, Western or Eastern, are not great at raising men to be in touch with their emotions. And realizing that you are infertile is a very hard blow to one’s manhood on many levels. One of the most concerning issues was worrying about what others were thinking or knew about my situation. Early on, it bothered me to think that they would find out. As I began to heal, however, I began to care less and less about what others thought. I simply can´t control other people’s minds and have no interest in doing so. I also realized that those who are close to me all know about the infertility and nothing has changed between us and how the view me as a person. The rest I leave in God’s grace.

Another realization over the last year is that infertility is not a disability in life. It is in fact the way that I was created. It is part of me. It is who I am. And although I can’t change it easily like, say, losing weight or getting more exercise, I can certainly change how I view it. I can shape my future in any way that I wish. I am the master of me.

The road I took that year was no easy one, but I made it through the year. Leaving this behind me, I can now move forward in my life. I have faced the demons and have come to terms with my reality. I now look upon the future with renewed eyes and see a future filled with happiness despite the fact that I cannot have children.

Please let us know if you would like to continue a discussion of these issues in an on-line forum…

A Year Without Answers

Paul Turek, MD — Mon, 12 Mar 2012 15:00:30 +0000

"Elemental" Courtesy of the Artist: A.J. Russell

This is a guest post from a patient who lives in Europe. He recently recontacted me about his experience with male infertility and how it affected him. Moved by his story and by his emotional fortitude, I asked him if he could share his remarkable journey with others.

“The day we met with Dr. Turek was a week filled with hope and happiness. Almost a year earlier, on the same day, I went through a biopsy with the result that there were no sperm. So when we found out about Dr Turek, this really felt like the last chance, the last hope. Therefore the decision to travel across the world to see him was an easy one. The visit and procedure went well, but, again, the result from mapping showed no sperm. And no answer as to why this is.

It has been a year since I spoke with Dr. Turek about these results, a year characterized by disappointment, anger, sadness and worst of all, no answers. There were simply no answers to be found. Why me? Why now? What now? Literally a thousand questions ran through my head interfering with my daily life, keeping me up at night and affecting my relationships. I had never felt anything like this before.

I wanted so badly to not feel alone in this. I wanted someone to understood my plight, without me having to explain every small detail, because you can´t explain this feeling.

I needed to talk about it. I just couldn’t bury it. But, who was I going to talk to? And what would I talk about? I felt isolated as there appeared to be a big taboo regarding this topic. Anyone I spoke to told me focus on other things in life. But how are you supposed to do that when all you think about is the fact that you can’t have your own children? I knew no one with a similar experience who would step forward and talk about his experiences and feelings. Google searches were pointless, as the Internet does not care and information on coping is useless.

That year was best characterized by the feeling of being lost and trying to find my way in darkness without a map or light. I felt that I was in a deep, dark place, especially when I tried to look forward into the future.

Feeling alone, I began suppressing everything. All feelings, thoughts and discussions were avoided. I told my close family that I did not want talk about this matter anymore. It was a buried subject for me, never to see the light of day again. The reason for this was that talking about this issue within the family only made things worse. One problem with this approach was that the bright spots in my life also suffered along side. The subject became an 800-pound gorilla that, although ignored, never left the room. Maybe the gorilla was bigger than 800-pounds as the family dynamics changed greatly.

Then I became angry, sometimes uncontrollably. This was when I could see that I was approaching rock bottom. The slightest annoyance, comment or action sent me into a furious rage where I often exploded at whomever was next to me. Many times it was my wife, which led us to the brink of divorce. We were both tired of fighting and there appeared to no other solution to end the fighting but dissolving the marriage. This moment was a real eye opener for me.

What helped keep me going to some degree during this time was my job. As a futures trader, my work was very involving and in the moment. Believe it or not, it was also logical and predictable, in a mathematical sort of way. It could be explained and reasoned with and while doing it, I could leave all my troubles behind. But I couldn´t hide in my job forever.

I turned the corner at rock bottom when I realized that if I did not start controlling my emotions and start being honest with myself, my life as I knew it would change dramatically. It was on that day, a very cold one in December, that I realized that I was just too exhausted to continue to fight with myself and others. I couldn’t bear to face another year continuing on the same as the last. So, I stopped lying to myself and began to face the reality of my emotions.”

The second and final part of this guest series will be available Monday, March 19th.

Fitting Into Your Genes

Paul Turek, MD — Mon, 19 Sep 2011 15:00:31 +0000

Change is the engine of evolution, and the source of infertility

“Why Me? I take great care of myself.”

I often hear this common question from men with low or no sperm counts who are unable to conceive. In fact, they usually are taking great care of themselves. The fact is, many cases of male infertility are actually genetic and have more to do with the cards that they were dealt.

“But my brothers, sisters and cousins all have kids…!”

Here where is gets a little complicated, as not all genetic traits are handed down the same way. There’s autosomal recessive and dominant, sex-linked, sex-limited, Mendelian and non-Mendelian, and even polygenetic and epigenetic. The thinking implied by this comment is Mendelian, which one of only a few ways to pass genetic traits along. The way infertility occurs is not necessary like that of heart disease or high blood pressure.

Genes and You

What is that saying? “Clothes make the man.” A more modern (and accurate) way of saying this is that “Genes make the man.” And with male infertility, it is becoming quite clear that genes matter a whole lot.

For 50 years, as men were evaluated for infertility, clinicians would simply use the term “unexplained” or “idiopathic” to describe much of what they saw. As the Y chromosome was found to have important genes for “maleness”, interest turned toward this chromosomal location to explain infertility as well. Then, in the mid-1990s, a colleague of mine discovered an area on the Y chromosome that could explain why a chunk of men had low or no sperm counts. Now, it is clear that the Y chromosome is central to normal male fertility.

It is thought that between 500 and 1000 genes are involved with sperm production. This is a reasonably big lot of the estimated 25,000 genes that exist in the human genome. However, currently, fewer than 50 genes have been definitively linked to male infertility. Some of these are on the Y chromosome, but many are not, making the story even more complex than originally thought.

My Answer to “Why Me?”

My long answer to the question “Why me?” revolves around the concepts that 1) there are two different genetic evolutions in the body, and 2) that your genes may be new to you and may not be handed down like clothes. It goes something like this:

Eggs and sperm (also called “gametes”) are responsible for the vast bulk of human evolution. They have a very long term view of where our species is going.
As a consequence, genes in our gametes constantly mutate and change, as change is the engine of evolution. Genetic change in our gametes is expected, nay necessary, for our proper evolution. They mutate rapidly and frequently.
On the contrary, genes in the rest of the body exist to support the work of the gametes, for the good of the species. So, the rate genetic mutations in this system is much lower. As the rocket (body) for the payload (gametes) the body must run fast, hard and true.
Given this setup, with evolutionary pressure high in gametes, new mutations occur far more commonly there than in the rest of the body.
Another way of looking at this is that if every mutation that occurred in our gametes was made manifest in our bodies, we would look entirely different from one generation to the next. Luckily, this isn’t the case, because the quality control “filter” is so good.
But it does explain why there is a lot more genetic change affecting infertility than one might expect.

Maybe it’s true that clothes make the man, but with male fertility it is also true that the clothes were newly purchased and not hand-me-downs.

Giving Up the Gavel

Paul Turek, MD — Sat, 02 Apr 2011 14:07:43 +0000

A gavel with teeth for this President…

In two days, I will hand over the gavel. It’s actually a meat tenderizer that I bought to run the meetings this year and it worked just great. A gavel with teeth. Regardless, I surrender it with mixed feelings. On one hand, a year as President of one of America’s leading academic societies is a lot of work. On the other, though, I feel like I am just getting started and that the ship is now running fast with sails full. As we all know from politics, systems with rotating leadership all have their virtues and vices.

The American Society of Andrology

The Society that I lead is the American Society of Andrology. It was founded in 1975 and has about 700 members, most of whom are academic researchers. I guess I have a soft spot for nerdy scientists who care about men’s health. Honestly, though, this group is unique. This week’s annual meeting in Montreal brings together a top-notch group of scientists and clinicians from around the world whose expertise, interest, friendship and collegiality lend to a remarkable cross-fertilization of science and medicine.

What the Heck is Andrology?

My mother still asks me this question. Andrology is the study of men’s health and, in particular, the male reproductive system. It involves all aspects of reproductive fitness, including fertility and infertility, erections, hormones and sexuality. As a reflect upon the Society’s position in the academic world, my elevator pitch is that this Society’s focus is on “The Science of Men’s Health.”

President’s Tribute

The year has been a good one: restoring falling membership, bringing financial stability, initiating a strategic plan and an endowment campaign, and brokering the merger of the Society’s academic journal with that of its European counterpart, the European Academy of Andrology, to ensure its future livelihood.

But, as with most endeavors, the people make the party and I must admit, my colleagues rose magnificently to execute the demanding projects that I put forth this year. And this means a whole lot. In fact, this and only this is substance of my final toast, a limerick, at the Welcome reception tonight. I probably shouldn’t leak it here early, but for you dear reader I submit:

There once was a crazy society,
Subscribed to by much notoriety,
Its goal, so sincere,
To study things dear,
Like sex, with the utmost sobriety.

But not only sex does it foster,
There is but a much longer roster:
Like sperm, prostate, erections,
And most epididymal sections,
And diseases like clap and zoster.

And don’t forget contraception,
The inimitable acrosome reaction,
And ejaculation that’s early,
With low libido that’s surely
A sign of hormonal malfunction.

So as we meet here in old Montreal,
Let’s remember these orders so tall:
To discuss, think and debate,
With friends old, new and irate,
The science to which we are called.

That Azoospermic Feeling

Paul Turek, MD — Tue, 08 Feb 2011 06:09:48 +0000

Was Van Gogh Azoospermic?

At the beginning of the office visit, I like to ask men with no sperm in the ejaculate who are unable to conceive a simple question: “What crossed your mind when you first heard that you were azoospermic?” The answers varying greatly but are very telling:

“It must be a mistake.”
“I shouldn’t have joined that fraternity in college…”
“It wasn’t the best sample I’ve ever done.”
“I was simply and utterly devastated.”
“I was in shock and then got really depressed.”
“It changed my life…I always thought that I would be a father.”

The Meaning of Azoospermia

Azoospermia is the lack of sperm in the ejaculate. It can be due to a blockage in the system (obstruction) or failure of the testicles to make sperm (nonobstructive). The most common reason for blockage is a vasectomy. Other causes include infections, prior surgery, injury or congenital absence of certain reproductive tract organs. Failure to make sperm can be due to exposures (hot tubs), medications, varicocele, a history of undescended testicles, cancer and cancer treatment. However the largest chunk of men with poor sperm production have none of these issues. Instead, they have a subtle genetic cause: either they are missing genes on the Y chromosome or have other chromosomes harboring subtle alterations that do not otherwise affect their health or lives.

So, like Captain Renault in the movie Casablanca, most men with azoospermia are “shocked, shocked!” because they feel so normal in every other way. And the vast majority are normal (as normal as men can get) in every other way. Most of the things they worry about, like college indiscretions, are exposures that are entirely reversible with time. My response is usually to allay fear and guilt by saying: “This is not something that you have done to yourself; let’s see if we can do something about it at this point.”

Treating Azoospermia

In fact there is a whole lot that we can do with azoospermia. Men with blockages can often be unblocked with microsurgery, one of my favorite things to do. This gives them the chance to conceive naturally again. And most men with poor production as a cause of azoospermia will have pockets of sperm in the testicles that can be identified by techniques like sperm mapping and that can be used for high-technology pregnancies.

What I have learned after caring for hundreds of azoospermic men over two decades is that they really don’t care what their sperm counts are as long as they can be fathers. And once they are fathers, it is clear that that “azoospermic feeling” goes away, as it should.

The Man in the Mirror

Paul Turek, MD — Sun, 05 Sep 2010 04:50:57 +0000

For best fertility: look in the mirror

What is the most commonly asked question in my male fertility practice:

“What can I do to improve my sperm count?”

My answer:

“Treat your body like a temple; all things in moderation.”

I’m sure that this is a disappointing answer for many men, but it’s true. There are no tricks here. Here’s why: Unlike food or water, which we need to live from day to day and without which something will break down in our lives, sperm production is different.

The sperm making process, termed spermatogenesis, wants to run hard and fast—and all the time. The body is happiest making 1200 sperm/second in the normal healthy male. It would rather make sperm than not, given the chance. It is similar to the heart that wants to beat or to a self-winding watch.

So all one can really do is to try not to poison the sperm making process by unhealthy living. Fevers, illness, tobacco, hot tubs, obesity and poor eating habits are all examples of toxins or exposures that “sicken” the body and slow down sperm production. Stay healthy and sperm numbers should be just fine, thank you. A good reproductive body is a good healthy body.

Of course there are reasons to have low or no sperm counts that do not involve impaired sperm production, including vasectomy and lifelong or acquired blockages, but these are unusual. In addition, with infertility due to genetic causes, low sperm counts are likely the consequence of being handed fewer than normal numbers of testis stem cells, the cells that produce sperm. But even in cases of genetic infertility, the stem cells that are present are working their hardest to make as many sperm as possible. It just may not be enough sperm to get out of the testicle and into the ejaculate.

And yes, we have good ways of improving the sperm numbers in men with low sperm counts, but with these treatments we generally will not improve sperm counts to numbers that exceed those that the man would naturally have if he were healthy.

So, lifestyle and daily habits matter greatly for sperm production and fertility. I know it’s trite, but Michael Jackson was right: start with the man in the mirror.

Babies…Naturally

Paul Turek, MD — Sat, 14 Aug 2010 15:35:08 +0000

The magic bullet? You decide.

In my daily fertility practice, while trying to help couples to conceive, I’ve noticed a trend lately. Patients are less interested in using high levels of “assisted reproduction” to have children. In particular, they would like to avoid in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), the Cadillac of all techniques. Even before they meet me, they have decided against it. Not all couples, mind you, but certainly more than before.

Briefly, IVF-ICSI is a busy month for women. It involves stimulating them with daily, injectable hormones during the first half of the menstrual cycle to generate more eggs than normal within the ovary. Ovulation of eggs is induced by injection of a second hormone, which is closely followed by egg retrieval using needle aspiration under anesthesia. Retrieved eggs are then stripped of their cell coats in a dish and a single sperm is individually injected into each egg by an embryologist. The criteria for choosing sperm are: good looking and hopefully moving. Eggs then become embryos in a Petri dish and are transferred back to the female reproductive tract three to five days later, depending on how they develop. Extra embryos can be frozen for future use. A pregnancy test is obtained two weeks later.

As a male fertility specialist whose practice mantra has been “treat the male, cure the disease,” I find this trend very interesting. Assisted reproduction is almost always an option for couples, but I have spent a good deal of time publishing research showing that classic male infertility treatments such as varicocele repair and vasectomy reversal are very cost-effective ways to conceive compared to more expensive techniques like IVF-ICSI. On the other hand, these techniques are the only option for many men with azoospermia, or the absence of ejaculated sperm, and I am glad that it exists for this.

I wrote down what patients said when I asked them why IVF-ICSI is not an option on the table for them and here are some of the responses:

“It seems pretty invasive and unnatural.”
“Isn’t it relatively new?” (IVF is 32 years old, ICSI is 18 years old)
“Who selects the sperm?” (Since it is not God or Darwin)
“Wasn’t ICSI developed as an experimental mistake?” (Yes)
“How do we know that those are our eggs and our sperm? (Rare)
“It’s only a single try at having children.” (Maybe two)
“Isn’t there an issue with higher birth defects and syndromes in babies” (Very likely)
“Are our children going to be infertile?” (Unknown)
“We’d prefer to have the hope of trying every month at home.”
“IVF-ICSI is too expensive”

What I think is happening is that as IVF-ICSI is being offered to consumers more often than ever (currently 1-2% of U.S. babies are born from these techniques), patients are becoming better educated about the technology and are making more informed, personal choices. My gut also says that good, old-fashioned sex has a strong following among infertile couples as a way to conceive. In the words of Woody Allen in Annie, “that was the most fun I’ve ever had without laughing.”

Synthetic Cells: The Latest Vinyl?

Paul Turek, MD — Mon, 24 May 2010 05:16:26 +0000

Synthetic cells: true science or fashion vinyl?

Believe it or not, science has now claimed to have made “synthetic life.” Life created from non-living substances. J Craig Venter and colleagues, after a decade of work, produced a man-made version of the entire DNA content (genome) of a bacteria (adding in a couple of harmless “watermarks” to track it) and inserted it into the shell of another bacteria after removing its DNA. And, lo and behold, the artificial genome starting making proteins and the man-made bacteria began to replicate.

You may remember Craig Venter as the man in corporate biotech a decade back who challenged the U.S. government in a race to completely encode the entire human genome. The Human Genome Project was completed in 2003 and jointly announced. This is a beautiful thing but Venter wanted to “own” and patent the human genome and charge others for using it as a resource whereas the U.S. government insisted that it be made publicly available, which it is.

Is this really synthetic life? No. Essentially, Venter performed the equivalent of gutting a computer and then entirely reprogramming it. Is this an important scientific achievement? Absolutely, a tour de force, since technology has been limiting this work for years. Recently, however, there has been a 100-fold increase in the length of genetic material that can be manufactured from raw chemicals in the lab. Without a doubt, science has been dreaming about this kind of work for three decades and recombinant DNA technology is an early product of this movement.

So, an entirely “artificial cell” was not produced by Venter, as the control station was man-made, but the rest of the cell was not. My only hope is that this is not just another “pleather” (plastic and leather) product in our lives. As Lily Tomlin said: “[even] vinyl leopard skin is becoming an endangered synthetic.” On the contrary, this work may have advance science sufficiently to begin the manufacture of designer cells, good or bad, that can clean up oil spills, dynamite and waste water, dispose of nuclear waste and deliver antibiotics, chemotherapy, testosterone or Viagra to hard to reach but important areas of the body.

Does Male Infertility Begin in the Womb?

Paul Turek, MD — Mon, 03 May 2010 04:59:19 +0000

This Da Vinci fetus is way past the critical window of exposure.

A relatively alarming study was published a couple of years ago that suggested that a pregnant woman’s behavior can determine the fertility of her unborn son. Sperm quality from 387 men was compared to beef consumption their mothers reported while pregnant with them. They found that the sons of “high beef consumers” (>7 beef meals/week) had sperm counts that were 24% lower than in men whose mothers ate less beef. Interestingly, sperm counts in the sons were not related to mother’s consumption of other meat or to the son’s consumption of meat. In essence, the author’s thought that estrogens in beef consumed by women may alter the testis development of their unborn sons and may adversely affect the son’s fertility. Similarly impressive decreases in semen quality have been described in the sons of women who smoked during pregnancy.

Sounds almost biblical, doesn’t it? I bring this up because of a point that I made in last week’s blog. In “The Curse of Women’s Urine,” I mentioned how xenoestrogens or environmental estrogens have been shown in animals to act at a very precise point in the developing male fetus and result in intersex conditions at birth or infertility as adults. Well, as the study of mothers’ beef intake reveals, the same issues may also exist in humans. As Aristotle once said: “At his best, man is the noblest of all animals; separated from law and justice he is the worst.”

Time for a quick lesson in biology. When do testicles develop in humans? Believe it or not, when male fetus in just 4 weeks old, the location where the future testis will be is organized (the urogenital ridge). Two weeks later, the primitive germ cells (sperm precursor cells) migrate to the urogenital ridge and set up what is to later become the testis. About 1-2 weeks after that, “sex cords” develop in the primitive testis, setting up the architecture of the mature organ. So, by 8-12 weeks of pregnancy, the human testis is virtually a complete organ, holding within it all of the potential it will ever have.

So the “critical window” of exposure for the human testis, that period in which even a potentially small exposure could wreak significant developmental and long lasting havoc, is about the time when women actually just realize that they are pregnant. The time of morning sickness and painful breasts.

So, does male infertility begin in the womb? Still not clear, really, as all studies have flaws. For example, in the study of beef eating pregnant women, the cohort of son’s whose sperm counts were so thoroughly examined were ALL fertile. That’s right, their wives were all pregnant. Oscar Wilde couldn’t have said it better when he said: “The pure and simple truth is rarely pure and never simple.”

Genome: Repair Thyself

Paul Turek, MD — Mon, 22 Mar 2010 05:02:15 +0000

How damaged is your genetic sheet metal?

Imaging parking your car at home after work and all the nicks and scratches are removed while you sleep, before heading to work the next day. All shiny and new, polished even, while you sleep. Believe it or not, this is normally what happens to your genes and chromosomes on a minute-to-minute basis. DNA mismatch repair is a constant and vigilant process, occurring in all cells of the body. Why the biologic vigilance? Well, It keeps us whole, healthy and cancer free.

About 11 years ago, we published a paper showing for the first time that infertile men can’t repair the errors normally encountered in their DNA as well as normal men. This was startling news in part because it implied that infertile men may be more likely to develop other problems later in life, including cancer. Why cancer? Because the development of cancer has been associated with the inability to normally repair the frequent daily errors that occur to one’s DNA as the body’s cells divide and renew.

Today, however, we know much more. We know that testis cancer is 3-fold more likely to occur in previously infertile men than in fertile men as they age. And our latest research has shown that prostate cancer, thought to be a disease exclusive to older men, occurs more seriously and more commonly in previously infertile men.

So what does this mean? Is male infertility the first sign of a larger problem in our species? It is the ultimate medical problem of a species trying to reproduce? Well, honestly it isn’t entirely clear. However, to me it indicates that male infertility should certainly be considered an insurable and real medical condition that should be taken as seriously as a heart attack. Even more worrisome is the issue of whether the use of sperm from severely infertile men is putting their offspring at even higher risk of medical issues than that experienced by their fathers.

So do not ignore the infertility issue when it strikes and get that male partner evaluated by a specialist. Teach him to perform testicular self-examination, a simple maneuver performed once monthly in the shower that has far more potential to extend his life than even exercising or weight control. Educate him about prostate cancer so that he does not ignore the powerful screening tools available to find it early. The age of innocence is over. The warning signs are now clear; get men the care that they deserve.

Your DNA Barcode

Paul Turek, MD — Mon, 22 Feb 2010 02:03:04 +0000

Can we be DNA barcoded like a soup can in a grocery store?

How many of you would take a blood test to learn exactly how long you will live? How about whether or not you will become demented? Since the Human Genome Project ended, the genes and mutations associated with a vast array of diseases are being discovered daily and it is pretty easy to just put them on “chip” and make them available to the public.

Don’t get me wrong; gene testing already has already improved our lives. Such tests can clarify a diagnosis and better direct care, while others allow families to avoid having children with life-threatening or disabling conditions. They can be used to prevent disease before it happens, as with monitoring and removal of colon growths among those who have a gene for familial polyposis, and can diagnose common iron-storage diseases early enough to treat them and prevent them from becoming fatal. They can also help to positively identify murderers two decades after the crime.

One real problem is that many commercialized gene tests are targeted to healthy people who might be at high risk because of a strong family medical history for a disorder. Unfortunately, because of how complex we are as biological organisms, the tests give only a “probability” for developing the disorder. That means that some people who carry a mutation may never develop the disease. Another limitation is the possibility of laboratory errors. What this means is that the tests are not perfect and could be wrong.

And what happens to your job prospects and health (or life) insurance rates when it is learned through genetic testing that you might develop a significant disease? Well…nothing. Because of the federal GINA Law (Genetic Information Nondiscrimination Act) passed in May 2008, insurance companies and employers cannot discriminate on the basis of information derived from genetic tests. So, genetics has now been added to the list of characteristics first embodied by the Civil Rights Act of 1964, that states that U.S. employers cannot discriminate according to race, color, national origin, sex, or religion. And this is good.

So, go ahead and take the “23 and Me” “DeCode” or “Navigenics” genomic screens if you so desire. Get to know your DNA barcode. Maybe you will get an idea of what may be around the corner for you. And maybe, just maybe, you will take better care of yourself knowing more about your genes. Just understand that many in the medical community feel that uncertainties surrounding test results, the current lack of available treatment options, the tests’ potential for provoking anxiety and social stigmatization could outweigh the benefits of testing. You know the saying: “Too much information…”

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A Short History of the Y Chromosome

Paul Turek, MD — Wed, 23 Sep 2009 00:59:50 +0000

The Y chromosome: diminutive but cool.

Among the many chromosomes in a man’s body, the smallest one with the largest personality has to be the Y chromosome. With it, you are a male; without it, you are a female, with few exceptions. More than any other chromosome, it really defines who you are.

The Y chromosome controls other traits as well: hairy ears, tooth enamel, and stature to name a few. But for the longest time, the Y chromosome was also considered home to a lot of “junk DNA” that we thought had no purpose. We now know that much of this DNA has a purpose and that the Y is the home of many important male fertility genes.

Before its association with male fertility, the Y chromosome was widely considered a genetic black hole, a chromosome that evolved as a broken remnant of the X chromosome. We knew that the “maleness” gene was on the Y and a few other genes. However, since the Y chromosome has been fully undressed as a result of the human genome project, we now know that it is very unique, even special, and that it evolves in its own special way to keep men men.

The Y chromosome, and its neighbor the X chromosome, evolved into “sex” chromosomes hundreds of millions of years ago. This is important because many species do not have a chromosome for each sex like we do. Some species become male or female based simply on the environment in which they find themselves. Imagine that! A boy in the Artic but a girl in the Caribbean. At first, the original sex chromosomes probably evolved as a pair of two X chromosomes. Then, 150 million years ago, the Y chromosome made its break from the X chromosome. Basically, it stopped associating with it and this led to our current X-Y system of sex determination. I guess this is when men really became men.

As it works now, the single Y chromosome has no partner with which to swap genes when sperm are made (at a normal rate of 1200 sperm/heartbeat!) This “swap meet” of genes that occurs when new sperm are formed is an important repair process for the 22 other chromosomes and is absolutely critical for our evolution as a species. In fact, this is the source of our evolution. So, now that the Y chromosome has become isolated and less of a team player, is it doomed to extinction? More importantly, are men are doomed to extinction?

So how does the Y chromosome survive and repair itself, living alone in isolation while the world is changing around it? Well, we now know that it manages very well on its own, thank you. And this has probably been true for about 5 million years. Although it no longer swaps genes with the X chromosome, from which it came, the human Y chromosome is able to swap genes with itself to discard bad genes. It’s called gene conversion and no other chromosome does it. Just the Y. How uniquely male.

Basically, essential Y chromosome genes are arranged in a series of eight “palindromes,” or mirror image sequences, each of which folds like a hairpin in which its two arms come together. Then the “DNA checkers” compare the two arms for any differences and convert a mutation back to the correct sequence, thus saving the Y’s genes from mutational decay. So, the older “junk DNA” thought to exist on the Y chromosome is now known to represent DNA that it critical for its survival. One man’s junk is another man’s treasure. And so it goes, the Y lives on, and men do too.

Stem Cells, Snake Oil and You

Paul Turek, MD — Mon, 18 May 2009 15:19:10 +0000

Stem cells are past the snake oil stage of medical treatment

We’re way past bottled snake venom now. The new miracle medical cure lies deep within us, in our stem cells, if we can only figure out how to tap into them. 100 days into President Obama’s term, and it seems that the scientific community here in the U.S. might just be getting the fuel it needs to make major headway. The ban on using federal research money for stem cell research has partially been lifted, and I imagine that more funding is to come. A wise investment, I say. The potential for stem cells in medical care is simply enormous. I say this without hint of idealism, or romance, since I myself have seen what stem cells can do in my research with Stanford.

True stem cells are “pluripotent.” That is, they have the ability to become all of the different types of cells in the body. They could be used to rebuild or replace damaged tissue that is difficult or impossible for our own bodies to repair. Take nerves for example. If nerve cells degenerate, as occurs say with multiple sclerosis, one could apply stem cells to replace those degenerated nerve cells. These same stem cells could also replace damaged tissue associated with lung cancer, or Parkinson’s disease, or diabetes. Many conditions, including these, can currently be medically controlled, and made easier to live with, but they can’t be cured. Stem cells may change all that. For example, if eyesight has been lost due to corneal damage, we may be able to use stem cells to grow a new cornea, and restore lost vision.

There are many hurdles to overcome, some of them highly technical problems dealing with how to get from point A to point B. And cells that come from someone else can potentially be rejected. Even still, there are questions that may never be satisfactorily answered, ethical and cultural questions. Truly pluripotent stem cells are currently taken from embryos. When embryos get older, we call them fetuses, and when they are born, we call them children. The meaning of taking basically the seedling of a human being to treat another isn’t easy for some people to swallow. For others, the idea of cell-based therapy goes against deeply rooted notions of what is natural on this good earth. How you feel about this reaches into the most sacrosanct places in the heart and mind.

But there are other possibilities besides taking stem cells from embryos. “Adult” stem cells are stem cells made not from embryos, but from the tissues of fully grown adults. Bone marrow is a good example. Within bone marrow, special cells exist that can create all the cells within your blood. It could be that almost every tissue in the adult body has some kind of adult stem cell within it. Such cells might be able to be harvested from the same patient who needs treatment. Manipulated in a dish, they could be coaxed into other tissues, just like embryonic stem cells. This would avoid the issue of rejection discussed earlier, as well as the ethical questions raised from using embryonic stem cells. Currently, this coaxing is only possible with the help of viruses that introduce specific pluripotency genes into the adult cells and transform them into embryonic like cells. But who knows what tomorrow will bring? As I said, I have seen the potential already in a petri dish. More on that in my next posting.

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What we found: Male infertility and Cancer

arthurofsun — Thu, 19 Mar 2009 17:35:25 +0000

The genetic complexity of sperm and precursor cells when the chromosomes are painted is similar to that of constellations of planets and stars, and look very similar.

So what did we find?

The study showed that men who are infertile have a much higher risk (3 times) of developing testis cancer later in life than the average citizen. And this was based on some serious number crunching. We worked from a huge database of over 51,000 infertile couples who sought care over a 22 year period in California. The male partners were cross referenced with a California cancer registry to figure out who among them developed testis cancer as they got older. Among infertile couples in whom the male partner was not the reason for infertility, the future risk of testis cancer was the same as in the general population. However, among infertile men who were themselves the cause of the infertility, the risk of future testis cancer was 3 times higher.

So what does this really mean? Well, first of all, it confirms studies from Europe that have suggested the same thing is happening there. This confirmation in a U.S. based study is important, because the rate of testis cancer in many European countries is much higher than it is in the U.S. It also implies that there may be a connection of some kind between male infertility and testis cancer.

But what kind of connection could exist between male infertility and testis cancer? Well, environmental exposures might link these two conditions. However, the kinds of substances that could do this are still unclear. Estrogenic compounds such as bisphenol A, phthalates and pesticides have garnered much press lately as they alter sexual development in animals, but have not been definitively linked either to testis cancer or human infertility.

The connect, I think, may be even more basic: it probably involves genes and gene mutations. About 10 years ago, we and others reported that severely infertile men have more trouble than other men in properly repairing the daily breaks and kinks that occur in everyone’s DNA with daily use. Because faulty DNA repair is clearly associated with cancer in humans, this led us to surmise back then that infertile men with faulty DNA repair might have a higher risk of cancer later in life. And voila! The results from the recent research appear to support this idea.

For the time being, the risk holds only for testis cancer, but who know what future research will show? Based on this, I recommend that all infertile men certainly be evaluated by a urologist with a good history and physical examination. They should also be taught testicular self examination as a screening tool to detect testis cancer.

Infertility as a window into men’s health? As a shift in thinking, it certainly does shine a new light on the problem.

Male Infertility and Cancer Later On