Elvan Böke, biologist: "Erectile dysfunction is investigated much more than female reproduction"

Elvan Böke (Karabük, Turkey, 36 years old) is the daughter of a physics teacher and a metallurgical engineer.

Her life has been marked by two transcendental events;

cartoons

on TV.

Looking behind her, this molecular biologist realizes that at the age of five she was already interested in mutant animals, essential for scientific research.

At the age of 12, Böke learned that his mother had become pregnant.

She was 38 years old;

it was a risky pregnancy.

The little girl accompanied her mother to the doctor many times and she learned from a very young age the risks of having children at that age, such as a greater chance of miscarriage or birth defects in the baby.

An amazing fact was also recorded on fire.

At birth, women —like the vast majority of mammals— already carry in their ovaries all the eggs they will have for the rest of their lives: between one and two million, enough to populate a medium-sized city.

At puberty, these oocytes, or immature eggs, begin to mature.

At this point there are only about 300,000 left.

Only about 400 mature eggs are released during a lifetime, usually one in each menstrual cycle.

When there are only 1,000 oocytes left, menopause will begin and reproductive life will be over.

Tens of thousands of oocytes are lost along the way without reaching maturity, and no one knows why.

“When I explain this at conferences full of biologists, very smart and prestigious people, I am very surprised that they don't know it,” Böke explains.

In other words: we humans live with our backs turned to the fascinating cells that have made our life and that of the rest of the human beings on the planet possible.

After studying genomics in Turkey and receiving a doctorate in the United States and the United Kingdom, Böke has directed the oocyte biology group at the Barcelona Center for Genomic Regulation (CRG) since 2017.

The scientist has just received a prestigious grant from the European Research Center of two million euros to investigate the basic biology of oocytes and their maturation.

These cells are the only ones in the body that are immune to aging for decades, and it is not very well known how they do it.

Getting to understand it could alleviate the enormous demographic problem that Spain and many other developed societies face: mothers are getting older and fewer and fewer children are being born.

Ask.

Of all the cells in the body, why did you decide to focus on the ova?

Answer.

Because oocytes are perhaps the most interesting cells in the body.

They are in charge of giving life to the new generation, they are the largest cells in the body and also some of the oldest;

And they are really beautiful too.

In fact I think that, together with neurons, they are the most beautiful.

Despite all this, they are much less studied and as a woman I am disappointed with how little we do research and understand our own reproduction.

Q.

Why do we know so little about the ova?

R.

Because it is difficult to work with them.

In other fields of biology you can grow cells in the laboratory, but oocytes do not multiply nor do we know how to create them from scratch.

You have to sacrifice an animal to remove its ovaries and get those cells.

In addition, in each animal there are not many oocytes, it is not like the rest of the cells that number in the millions, but only a few thousand in a mouse.

Historically there has been a shocking lack of funding for this type of research.

It has been a subject that has not interested.

Q.

Why?

A.

In 1980, in a developed country like the United States, the majority of mothers were between 18 and 22 years old.

In 2016, more and more women were having their children in their thirties, and the trend continues, mothers are getting older.

For a long time, governments and science funding bodies didn't feel like this was a topic worth investing in, because there wasn't really a fertility problem.

Now there is.

This has ceased to be just a female health problem to be a demographic emergency that affects us all.

Q.

You have just received two million euros from the European Union. What exactly do you want to study?

A.

Any type of cell in the body ages, including neurons, which show signs of wear and tear with age.

If the ovules accumulated the same damage, we would basically become extinct as a species in two or three generations.

But the truth is that they do not accumulate defects with age, they do not age.

So, when a woman has a child at 38, that child is no different than that of a 20-year-old mother, because the oocyte from which she came had not aged.

In fact, demographic studies suggest that the children of older mothers tend to be healthier and achieve higher levels of education.

Q.

Is it known why?

A.

It is not clear.

In part, older mothers tend to have a higher educational level.

It may also be that they are more aware of the first signs of illness in their children and know how to identify them better.

[In 2016, a study by the Max Planck Institute for Demography, in Germany, argued that, at the population level, children born to older mothers have better health and a higher level of education.

On the one hand, pregnancies in mothers aged 35 or over tend to have more complications.

But, according to the paper, the benefits of having children later in life outweigh the risks].

Q.

So does having children later and later make sense?

A.

Sure.

I had my daughter at 34 years old.

I wanted to finish my education first, build a career, find a partner.

It is logical that we are having our first children, more and more entering our thirties.

But it is important that we are aware of what it entails.

I know women my age or younger who take fertility tests and discover that their ovaries are those of a 40-year-old;

they have very few eggs left.

One thing we could do now as a society is have a widespread fertility testing program.

Thus, let's say that at the age of 18 women could have an approximate idea of ​​their fertility and better plan their lives.

Q.

When does the health of the oocytes begin to deteriorate?

A.

It is gradual.

At about age 35 a considerable decline begins, but in reality it varies greatly.

Fertility clinics sometimes explain it as if there is a certain age beyond which you are lost and will never be able to have children, but this is not true.

Q.

You can measure the ovarian reserve, right?

A.

Yes, but it is an estimate.

Reproductive biologists discovered that oocytes that begin to mature and grow release a hormone.

The levels of this molecule in the blood are related to the number of eggs you have left.

This is the system that fertility clinics use to measure ovarian reserve.

But it is important to know that it is an indirect approximation.

It does not tell you what happens in the reserve, which is where your unripe oocytes are.

Q.

Do assisted fertilization clinics explain these limitations well to patients?

R.

I think they are not missing the truth, but they embellish it a lot.

An example is egg freezing.

The approximate success rate, that is, a healthy baby being born from a frozen egg, is less than 5%.

I don't think many clinics talk about this with their patients.

Q.

Could it be known at birth when you will stop being fertile?

A.

No, because there is no data to estimate it reliably.

We would need data on many females at birth.

Even if we started taking them now, we would only have the model 60 years from now.

Q.

How do the eggs stay young?

R.

It is a discovery that we have just made and that we will publish in the journal

soon.

In almost all other types of cells, this topic has been studied for many decades, but until recently no one has been interested in how oocytes generate energy.

What we have seen in mice is that these cells are special.

Inside the cytoplasm of cells [the jelly-like substance inside them], many proteins are made that do their job, and then they are broken down and broken down.

With age, these cleaning mechanisms stop working well and poor protein aggregates form.

This is what happens in neurons with Alzheimer's, for example.

What we have discovered is that the oocytes also generate this waste, but they keep it in a special compartment, like an airtight garbage can that is kept insulated.

In this way the waste does not cause them problems or aging.

And the most interesting thing is that just before being fertilized by a sperm, the ovules expel that garbage can, probably so that it does not cause complications when it comes to forming an embryo.

Q.

Why do you accumulate garbage until then?

R.

_

We think it's because they don't want to waste energy.

Q.

And if they can stay young, why do they suddenly grow old at a certain age?

A.

We really don't know.

It's like our car broke down.

We know it's broken, but not why.

Q.

What kind of experiments are you going to do to find out?

A.

Much of our work is done with animal oocytes.

Human oocytes are provided to us by the Hospital Clínic de Barcelona.

They basically come from women who have to have their ovaries removed.

Q.

What kind of experiments are you going to do?

A.

Last year we published a study that showed that mitochondria, the cellular organelles responsible for producing energy, have to be turned off in some way to avoid generating harmful waste.

So let's compare young and not-so-young oocytes to see when they start to go bad.

We will do the same with those new compartments of protein aggregates.

We'll see when the engine starts to leak and misfire.

Because it is brutal that for decades it has simply been accepted that after 40 years the system stops working, just like that.

The problem is that we didn't even know what parts the engine has.

Q.

Could all this basic knowledge allow women to have children at later ages?

A.

It is enough for me to know that this can help women to have children in their fourth decade of life.

At about 60 women enter menopause.

What I do think we can do is slow down the decline of the eggs until reaching menopause.

So instead of starting the deterioration at 33, start at 42, for example.

In Spain, the age at which a woman has her second child is about 37 years and even then there are many risks of abortion, for example.

Q.

What do you think human reproduction will be like in 50 years?

R.

I am optimistic and I would like to think that not much will change.

But it probably does.

It will be much more technological than now.

The percentage of children born through assisted fertilization is skyrocketing and will probably be much higher in 50 years.

Q.

You comment on another surprising fact: one in four women is infertile and we don't know why.

A.

Exactly.

We have no medical explanation.

In men, the rate is one in ten.

And we don't really know why either.

Q.

And is there more research on male than female fertility problems?

R.

Yes much more.

If we look at the main repository of studies on biomedicine, in the year 2019, for example, the last year of normal science before the pandemic, if you will, twice as many papers were published on sperm than on oocytes.

If we restrict it to studies of these cells exclusively in humans, the difference is seven times more work on sperm than on oocytes.

The latter are represented by 28 studies.

That same year, 1,157 papers on erectile dysfunction were published.

Much more research is done on erectile dysfunction than on female reproduction.

Despite this, the situation is improving.

More and more people are studying this topic.

A curious thing is that the vast majority of teams are led by women.

There are honorable exceptions, but the majority of us are women.

Q.

Is there any relationship between diet and female fertility?

A.

Both obesity and malnutrition drastically reduce female fertility.

We have seen that oocytes produce their energy in a different way than other cells.

And this method uses only fat and protein for energy.

Zero carbs.

And this probably tells us something about the mother's diet and her fertility.

Q.

Why are most mammals already born with all their ovules, what advantage does it have?

A.

Nobody knows.

I believe that the womb is the safest place in which a person can be.

There we are much more protected from any environmental interference than once we were born.

It makes sense that we develop the most important cells in our bodies, the ones that will give rise to the next generation, when we are safest.

We then expend a lot of energy and effort to ensure that those cells stay healthy for years.

If women continuously formed oocytes and, for example, had a high fever or drank a lot of alcohol, it would be very dangerous, because the oocytes contain almost all the cytoplasm of the future embryo.

Spermatozoa, on the other hand, are very numerous and hardly contribute to the cytoplasm.

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