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Male factor-toxins, chromatin and oxidative stress explained

Medically verified
toxins-oxidative-stress-male-factor
Ana Puigvert, MD
Andrologist , Reproclinic
From this event you will find out:
  • What are the primary pathologies of the male reproductive system?
  • What are the most common endocrine disruptors?
  • What is the role of oxidative stress in male infertility?
  • What toxics that surrounds us is known to affect male fertility, and how to avoid them?
  • How can I reduce toxins in my life?
  • What is the effect of paternal diet on sperm quality and offspring health?

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What is the effect of toxins, chromatin and oxidative stress on male fertility?

In this webinar, Dr Ana Puigvert, Andrologist at Reproclinic, Barcelona, Spain, has discussed toxins, oxidative stress and how it influences sperm quality.

Spermatozoa of infertile men are suggested to carry more DNA damage that increases the transmission of genetic disease. This is also due to oxidative stress, which is an imbalance between the amount of reactive oxygen species and the major cause of male infertility nowadays, and then we can even measure it. 

What are the most common endocrine disruptors?

For those elements that produce this oxidative stress, they are called chemical endocrine disruptors which are estrogen-like and/or anti-androgen substances that interfere in all aspects of the reproductive and sexual hormonal mechanism in men. It’s a great problem nowadays because we are surrounded by all those kinds of elements that produce not only toxins in fertility but also in the health of people. What they can do, they can imitate, replace, and transmute the side hormonal control system, and they can become an antagonist of the natural function of those hormones in the target organs. One of the most important of them is in the testicles.

They act in the hypothalamus through different hormones that FSH produce, the activity of certain cells that help to maturate the spermatogenesis. They can change it. They can irritate it. They can change the attitude, the feedback. They can do all what they want, and that is the great problem that sometimes we even don’t know what is happening. We only know they disorganize the normal activity of these hormones.

What do they look like? All that they, in our society, we are surrounded, produce directly or indirectly oxidative products or endocrinological products that can produce this alteration of fertility. What we are, the respiration, what we are eating, the leakage through the water, all of those kinds of things can produce these endocrine disruptors.

What are the primary pathologies of the male reproductive system?

They sometimes don’t act directly. They sometimes need, for example, water or different kinds of plastics that produce these kinds of alterations. Here you have all the pathologies that produce the oxidative stress directly to the spermatozoa. In-systems are infection, pollution, smoking, and drugs.

 

Our way, how we are living nowadays, diabetes, the quality, what you are eating also affects this. They produce abnormal spermatozoa. They alter the transit through epididymis that we have been talking about last week. And they affect the prostate, and they produce then finally infertility that we must evaluate when we have someone who has infertility.

How do they act? Through inhalation, skin contact, direct or indirect, have we seen intake, can be concentrated dependent. If it is more concentrated, it can be worse. It can indirectly through its metabolites and can act in a specific environmental situation. I remember one kind of plastic that was used for vegetables that don’t produce infertility or oxidative stress in men, but the metabolites in four degrees in the freezer can’t produce it.

It has been changed and removed nowadays. We don’t have this kind of plastic. Each of them can act in a specific or a summatory effect. If you have more than one of these substances, the summary effect of all of them can produce this kind of situation. They are very difficult to study and even to identify because we must know exactly how they can act, where they can act, and which kinds of different toxics can act more severely.

They produce:

  • Alteration and decrease of the fertility capacity. I’m talking about men and women, it’s the same thing. 
  • Alteration of the sexual function.
  • Alteration of the hormones like testosterone, LH, and Leydig Cells. 
  • Alteration of the sexual development in kids before growing up. 
  • Induction of cancer in many organs, such as testicular cancer. 
  • Alteration of all the axes of the production of hormones in the hypothalamus, pituitary and testicular. 
  • They can cause disorders, like the thyroid gland. 
  • Alteration of the autoimmune system can alter the sexual and reproductive male organs. 

The impact is terrible because they act, as you see here, in all those hormones that produce or participate in the production of the spermatozoa. 

In the testicular history, the histology is the match we can see inside the testicle. It produces:

  • An impairment of testicular evolution stops the growth of the testicular tissue.
  • An induction of tissue necrosis, meaning they kill the spermatozoa before being the spermatozoa. 
  • Leydig cell block that will not recognize LH and prolactin hormones, so they will not act. They will not produce testosterone. 
  • They change the morphology of the seminiferous tubules, where we have the stem cells of the spermatozoa to become mature spermatozoa. 
  • They alter the germ cells during the division of the chromosomes. 
  • They increase the percentage of tubules without spermatogenesis, so we will have a lower quantity of spermatozoa, and alters different types of maturation of the spermatozoa. 
  • They change the seminal fluid that is produced in the prostate. 

Here you can have a normal tubule, a seminiferous tubule, where you see the sperms, the mature spermatozoa, and here you have the Sertoli cells that help to mature these stem cells to become sperms.

Who is exposed? Everyone, all the time, is exposed to the intoxication of this kind of product. From the embryo, the evolution of the embryo, before the birth, that’s terrible. We are not protected, but the most important victims are the testicles of men. 

The testicles act as target organs where these disruptors of endocrine have the best affinity because it’s very protected. Testicles, as you know, are very protected, so they can act directly. They have a very straight relationship between testicles and toxins. 

We have seen already that they act in all those areas, in the testicles, in the seminiferous tubule, in the development of the stem cells until the mature sperm. In all the derivation of spermatogenesis, they can produce different types of mutations and the quality of the spermatozoa. They can change the quantity, movement, motility, and morphology of these spermatozoa. It’s very difficult to detect where they are. 

Already in 1980, the World Health Organization determined that reproductive toxicology has a very important speciality because every year we have more than 30,000 new products that can become, in the future, toxic for fertile people. This is terrible because almost all those kinds of studies look for different types of toxicity, but there are very low studies to protect the fertility of human beings. 

One of the persons that have worked a lot about it is Laura Valdenberg from Australia, and look what she says in 2017. 

Early life exposure to chemical and chemical mixtures can predispose individuals to diseases that manifest later in life.

In the embryo, and when you are another, you can have a dose of duration already. 

How low doses of chemicals during critical windows of development, like in embryos or just before becoming a baby, can alter gene expression, cell differentiation, tissue organization, and subtle ways that can lead to other diseases such as cancer, obesity, or infertility.

We know one of the most important is Bisphenol, which we can find already in the lactate memory gland, but even in women nowadays we can detect it and it’s very toxic for kids. 

What is epigenetics?

It has been defined today, generally accepted as the study of changes in gene function that are mitotic, in one of the moments of the division of the meiosis, and do not entail a change in DNA sequence. 

Well, these endocrine disruptors can change it. It’s a pathology, a very severe and difficult way to treat them. 

Another thing that is really very dangerous is that even you can have some generational inheritance of epigenetics. This means that the grandmother, if you have been in very straight contact of these kinds of products, can be transmitted to her descendants through those changes or mutations of these genes for chromosomes. 

These epigenetic changes produce male fertility and now we know it. The exposure of a gestating female rat during the period of gonadal sex determination is produced by an anti-androgenic compound that we can found it in some types in food or on different kinds of plastic, or methoxychlor, an estrogen compound. They act over the hormones and this produce alteration of the spermatogenic capacity and increase the incidence of male infertility. It can be transferred through the male germ to nearly all males of the subsequent generations examined.

Why? Because those changes of genetic alteration, the changes of the epigenetic is transmitted directly through the spermatozoa, and they produce different types of patterns of germlines. That is the reason that why kids can have these changes produced by their own father.

The ability of an environmental factor as an endocrine interrupter to reprogram the germ is terrible because they change directly the genetics of these persons. 

What toxics that surround us are known to affect male infertility, and how to avoid them?

  • Pesticides
  • Herbicide
  • Heat stabilizer
  • Chemical catalysts
  • Polluting plastics
  • Compounds of pharmacological product
  • Nourishing livestock
  • Food preservatives
  • Food diluents
  • Compounds of cosmetics: We’re talking about what can be absorbed through the skin.
  • Cleaning products. 

 

Here you have the different types of vegetable that can have a very high number of pesticides that can affect directly to human beings like tomatoes, pears, orange, lettuce, some teas like red or green tea from China, strawberries, we have it all around us. So, we must look how we can be protected of them. 

Eggs are one of the foods that usually have pesticides received higher than the European Union standard. Even in June 2017, German authorities in Hannover moved more than 73,000 Dutch eggs from supermarkets after they were found to be contaminated with fipronil. That is terrible because eggs are normal food that we eat very frequently. 

Phthalates are a sort of plastic that also can be very dangerous because they produce anti-androgenic, so they reduce the production of testosterone and affect the target organs, such as the testicle, even during the fetal development period until the puberty phase.

So, through all the growing of people can be affected. Nowadays, they are very controlled, but we are finding the phthylates in urine analysis. 

Human urinary phthalates, what I am telling, we can find those metabolites labelled in higher quantities in urine even in seven parameters as chromatins factor, sperm or reproductive hormones. They act in different ways, as you see in the chromatin of the sperm, in the spermatozoa or even in those hormones that help the production of those spermatozoa.

So, it is terrible because they not only act in one way, they act in different ways. It’s very important for human reproductive health the widespread usage of phthalates. The investigation needs to correlate them, but we know exactly what is happening nowadays. 

What can we do? Clinicians, and andrologists, must always attempt to identify the etiology of the possible testicular toxicity, and where it is acting and what they are doing to try to change this situation. 

Assess the degree of risk to the patient being evaluated for infertility, to know exactly what we can do to change this situation, and initiate a plan to control and prevent exposure to others once an association between occupation/toxicant and infertility has been established. That is very important because we can change some of those things. 

What are we doing?

  • We include counselling for a new way of life as prevention and treatment in male fertility.
  • We know that it is important to know what we are using for IVF techniques of reproduction because sperm that are made as a transport of the chromosomes can be the host that can introduce into the embryo those mutations. So, we have a transgenerational epigenetic alteration. 
  • We must make, nowadays it’s really important, an evaluation of the main factors in a genetic study that we can do, nowadays, most of them. Such as: 
  • DNA fragmentation index in sperm.
  • Aneuploides: Studied with testicular biopsy for meiosis, so we can see directly what is happening.
  • Study in general, with PGT in embryo IVF.

What can we do?

We must be informed, and we must inform. 

Here you have different types of information about plastic that, nowadays, we’re using. This one can contain bisphenol, so don’t use it or even don’t buy food that has this kind of product in its plastic. 

This is another indication, if they have phthalate please don’t use it. 

Don’t drink water directly through the plastic bottles, it is better to protect it without having light directly and drink it in normal water crystal water. 

What we can measure? 

Even nowadays, we can measure the quantity of PVC which is plastic in lipids that can cause severe oligozoospermia We must: 

  • Make multiple studies of the genetical situation in sperm
  • Meiosis study 
  • Genetic screening
  • Genetic counselling, because sometimes we cannot do anything about it.

The patient must know where is the limit and where we can do reproduction techniques. 

What are the recommendations?

I think this is the most important thing we’re talking about, such as: 

  • Don’t use plastic to eat food in the microwave.
  • Better not to use plastic for liquids.
  • Use glass, always. 
  • Try to eliminate fats of animal origin because the fat of animal origin has a very high quantity of endocrine disruptors and they’re very well used as an additive in food preparation. 
  • Try to use natural cosmetics, and don’t use it if you don’t have enough information about it. 
  • Always eat organic food and vegetables without pesticides and insecticides. 
  • Save your nutrition to have better health. 

What are the conclusions?

We must protect the future generation. 

  • We must be activists of our health. 
  • We are responsible for the future generation.
  • We must be responsible for the continuity of humans and their ability to reproduce correctly and in a natural way. 

The scientific society will have to position itself to protect lobbies of power. That’s very important. We must be seriously taking care because, nowadays, more than 40% of people are looking to have kids and most of them have many fertility issues due to toxic products that the governments must take it out from the market to protect the future generations because alteration, quantity and quality, clearly puts human reproduction really at risk as we have seen already. 

Moreover, the increased incidence of oncological pathology in young people as cryptorchidism, alterations of spermatogenesis and many other alterations are marking us that we must take into account professional responsibility and changes of approach in infertility treatments. 

These are almost new studies that we are already making to detect and to know what is happening with these endocrine disrupting chemical products and how they are attacking. It’s an attack against the spermatozoa and they use their own testicles as a target organ to destroy the testicle.

Male factor-toxins, chromatin and oxidative stress explained | FAQ

What would you consider normal sperm morphology for someone aiming for a natural pregnancy?

The World Organization has a limit of 15% of normal sperm morphology, that’s enough to have a normal natural pregnancy rate, of 15%.

In the 90s, it was 50%. What is happening nowadays is that the quality of sperm is going down, the seminal product is going down and down, so we’re adapting the situation to the normal, to the normal people who can have kids, but the truth is that we are going down and down. Nowadays, we consider normal 15% of sperm morphology.

My husband has 77% DNA fragmentation damage and has been prescribed turmeric tablets for 3 months. How effective is antioxidant treatment in bringing down damage?

77% is, really, high. In the labs now in Spain, they are saying that it is a pathology of around 30%. That’s not true. We have a lot of papers that demonstrate that until 50% of the DNA fragmentation, we consider normal, but higher than 60%, it is very pathologic.

 I think that the most important thing is to detect where the problem is, why your husband has this DNA fragmentation, the kind of food he eats, where he works because some jobs you are dealing in contact with toxic, even the frequency of relationships because you must know the epidermis damages the DNA fragmentation or spermatozoa. In this condition, I recommend people have their sperm screening with no more than three days of sexual abstinence. That’s important. 

We must look if he has an infection in urine or sperm. When you know exactly or more or less where the problem can be, you must try to change it or treat it, and you can be helped with antioxidant treatment. Sometimes, we cannot obtain good results, but I think that helps. I think that one of the best antioxidants for this kind of problem is the Q10 antioxidant products. They are very, very good. 

If you don’t have any kind of natural pregnancy and your husband continues to have 70% of the DNA fragmentation, then the best way to have a kid is to have an IVF and take the spermatozoa directly from the testicle. Those are the youngest ones, the best ones normally. 

If the endocrine disruptor is not affecting the testicle, then we can know it before because when you make a medical history and a physical exam, you make an exploration of the testicle, and you can know more or less if you will have any problem there. You must make a study of spermatozoa, you can do a lot of things to take exactly where is the problem.

What is the method to test for toxicity in our bodies?

It’s very difficult because toxicity is very, very wide. Toxicity is everything, the plastic of this table can affect us. The most important thing is to live the most natural way of life as you can. Interactively, if you make blood screening, you can see important changes of each of the organs as the liver, kidneys, and there you can find impact of the toxicity in your body.

You mentioned there are endocrine disruptors in animal fats, are there also endocrine disruptors in animal/meat products as I imagine most of them contain fats?

 Sure. It’s like this, more of the animal food that they eat has this endocrine disruptor. I don’t know if you remember more or less 15 years ago, there was a very great problem with the meat that they were finding estrogen-like products, that they were using to grow very quickly those animals, like chicken. So, you will find these endocrine disruptors in meat in all kinds of products because all of them have fats. Even, they give them fat because the fat is the product that makes the good taste of your food. So, they give them artificial fat to have a better taste of this meat.

My husband and I eat 99% organic food and generally quite aware of not using plastics, but our water comes in big bottles which we decanter in glass bottles. Does this make a difference? Likewise, is using silicone to cover heat foods better than clean film? How disruptive is having stainless steel and aluminium with acrylic artwork in our rooms, as I have a lot of artworks that I’ve designed using these materials?

I think you’re doing it very, very well. We must eat organic food, and this is a different way of life, a different way of living, I think that the pandemic that we are having all around the world must change a better way of life. I hope this, any of those things is making what you are doing. It’s really important, but unfortunately, it’s impossible really to change it so quickly. It’s one by one we might do. In the future, probably we will have better houses with less toxic products, and sometimes some of them are not toxic, but I think that normally what you are doing is quite well.

What test could be carried out on the sperm when undergoing IVF?

Well, one of the most important things that we must know is that sperm screening is only a photo finish of when a man ejaculates at that moment. You might know that from the stem cells until the spermatozoa, we need more or less two months and a half or three months, and men produce constantly through the tubules these amounts of spermatozoa that are changing. When you are undergoing IVF, first, we must know why you need an IVF, and if we can change something, we can try to have a natural pregnancy or a better result of this IVF.

There are a lot of different types of tests, but the most important thing is going to your doctor, to your andrology, and then he will make correctly his job to know what is happening and what he can change to have better results in IVF.

Can seminal plasma anomalies cause issues? Also, my husband’s sperm morphology is six, the range starts from four. Is this enough?

It’s enough for IVF. Less than four will have trouble and difficulties getting good results with them, but the most important thing is to know why he had this morphology alteration. He can have an infection, he can have a varicocele. Varicocele is terrible with sperm morphology, and if he can be operated on, we can have good results, even 42% of natural pregnancy, which is important. 

Imagine that in the United States, the health companies don’t pay for any kind of IVF if the man has a varicocele and is not operated. So, the doctor must do a physical examination, and if he detects a varicocele, he may choose what he must do, and normally he must make an operation to take out a varicocelectomy that’s not difficult. It’s only one hour in the operating room, and on the same day, he can go back home. He must rest three or four days, and it’s enough.

If you eat organic animal products, is that also a problem?

It is less problematic because it is very, very difficult to have food, even animal products, without any kind of toxicity. We know that we must eat less meat than we are eating in the occidental society, but it’s not a great problem because nowadays, the governments are taking very well care about the control of the organic products.

Are you saying we should eliminate all animal products? I thought fat was important to my hormones.

I say that animal products have a lot of fat with a lot of toxic products, but humans, are adapting year by year, time by time to the new situation of society. We’re not the same as 100 years ago if people that were living 100 to 200 years ago cannot eat what we are eating nowadays, because they will get very ill. So, we must moderate what we are eating and, naturally, it’s very difficult to change so quickly those things. It’s important to take care of what we must eat, the best thing we can. The problem is that the organic products, animal organic products are really expensive nowadays, so only a few people can eat about this kind of quality.

When testing bacteria or pathogens in sperm, does the sperm need to be alive or can you also get results on sperm that is tested a few days after the sample is produced?

Yes, it can be alive. It must be alive, but testing bacteria and pathogens in sperm is a different type of sperm screening. We make a biological culture to detect which kind of bacteria we have or kind of pathogens we have, and with it, we can make an antibiotically treatment, a specific treatment.

What is your view or your prediction on how male fertility is going to decline and look like in the future? 

Better than today. We have a very great problem because it is true that we’re doing a lot of studies, but the problem is that nowadays, people think that if you have IVF, it’s enough to have kids, and it’s not true. The problem we’re having with this kind of endocrine disruptive is more than only infertility, that it’s very serious. The population in Europe is becoming older and older, we don’t have because we don’t have new kids. People are older when they have kids, so we’ll have a very social, very dangerous situation because we haven’t changed for future generations. 

In the last 30 years, we’ve looking at the decline of the quality of spermatogenesis and sperm quality, and male infertility cases are increasing because most people think if I have 1 spermatozoon is enough to have 1 kid, and that’s not true. Men produce millions of spermatozoa because only very few have the fertility quality to fertilize those eggs.

One clinic provides postal service overseas, and I’m a bit worried about this as of course, the sperm wouldn’t be alive.

It depends on what kind of studies he must do. If it is genetic, there is no problem, but if it is a quality fertilization test, it must be alive. I think that some of those studies must be direct, and bacterial and pathogen sure, overseas is in few hours, it must be alive.

How can we improve sperm quality?

I think that we must choose medications that the patient must take depending on his medical situation. Supplements are just supplements; if you have a good diet and health, if you take care of your food and way of life, normally you don’t need any kind of supplement. You will need specific supplements depending on the situation of your sperm screening, your medical history, and your physical exploration. Then, we will choose one specific for it, but not all of them are good, even useful, some of them you’re throwing your money that doesn’t serve anything.

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