Yale Scientists Discover How Exposure to BPA Causes Infertility

Yale researchers may have solved a fundamental medical mystery: how bisphenol A (BPA), a ubiquitous plastics component, changes genetic chemistry and impairs fertility.

The Yale team's findings, previewed earlier this month to the Endocrine Society, a 14,000-member scientific and medical professional organization devoted to hormone system research and treatment, have intensified scientists' concern that exposure BPA, a synthetic estrogen that disrupts the endocrine system, may have grave consequences for human reproduction.

In an interview, study co-author Hugh S. Taylor, M.D., professor and chief of the reproductive endocrinology section at Yale University School of Medicine, said his team injected pregnant mice with BPA for just one week. After those mice, and a control group, gave birth, the scientists found that the genetic chemistry of female offspring exposed to BPA in the womb had been irrevocably altered.

A particular gene known as HOXA10, responsible for normal uterine development and fertility in both mice and humans, had been stripped of numerous so-called "methyl groups," each composed of a single hydrogen atom and three carbon atoms.

"We've discovered the exact mechanism by which BPA affects this gene," Taylor said. "This small group can have a powerful effect in turning genes on and off."

BPA scrambles mouse fertility gene's on-off switch

The HOXA10 gene's loss of methyl groups, Taylor and his colleagues determined, caused the uterine lining to become "hyper-responsive" to estrogen - and "out of sync" with the needs of a fertilized egg. A female mouse exposed to BPA in utero could conceive normally but her ability to carry a pregnancy to term might be compromised.

The chemical industry insists that neither the Yale study nor any other amounts to proof positive that BPA causes human infertility or other serious health conditions associated with the chemical in animal experiments.

The Yale scientists don't claim to have settled the many questions about BPA's impact on human health. They administered a higher BPA dosage to the lab mice than the general human exposure level. Their study, a work in progress, has yet to be published in a peer-reviewed scientific journal and corroborated by other researchers. They are planning more research on exactly how much, or little, BPA it takes to jumble a test animal's genetic chemistry.

"Permanent and irreversible" fertility loss

But their findings, which are concrete and specific, have already attracted considerable attention among a growing number of scientists studying BPA's complex interactions with living things.

"It's troubling that the changes are permanent and irreversible," Taylor said of the mouse infertility findings. "I don't want to say that at typical human exposure, there's clear and present danger, but there's enough concern that there might be to warrant further investigation."

BPA linked to heart irregularities

Two other research studies presented at the annual Endocrine Society meeting raised new questions about BPA and health:

• A University of Cincinnati team led by scientist Scott Belcher, Ph.D., linked BPA exposure to arrhythmias-- irregular heartbeats -- in female (but not male) rats and mice.

• Pioneer BPA researcher Frederick Vom Saal, Ph.D., of the University of Missouri-Columbia outlined a new estimate that Americans' exposure to BPA is probably significantly higher than the U.S. government's maximum "safe" dosage.

Hormone experts press for new restrictions on BPA and other chemicals

These and other recent reports caused the Endocrine Society, the world's oldest and largest professional organization devoted to research and clinical practice on hormones and endocrinology, to take the unusual step of issuing its first "scientific statement" declaring that BPA and other endocrine-disrupting chemicals in food, water and consumer products represent a "significant concern to public health." The society vowed to press for new government regulations to "decrease human exposure to the many
endocrine-disrupting agents."

Andrea Gore, Ph.D., a University of Texas pharmacology professor who helped spearhead the society's unprecedented move into public policy, said the weight of evidence is now substantial that chemicals that mimic or disturb hormone activity are corroding public health in many ways, from decreasing fertility to increasing incidence of some cancers. The scientific statement stressed that during critical developmental periods in early life, exposures to even very low levels of endocrine disruptors could have consequences decades later.

Developing children face most severe chemical threat

"If something disrupts the endocrine system of a fetus or infant," said Gore, "you may not know there's a problem until the exposed individual suddenly discovers she's infertile. That may not be until 20 to 40 years later."

Some cancer, she said, may be a delayed reaction to early exposures to environmental chemicals. "We believe the predisposition to certain kinds of cancers such as breast, prostate, uterine, testicular and otherhormonally-sensitive cancers, is set very early in life," she said. "Our likelihood of developing disease depends upon complex interactions between our genes and our environment - and changing the hormonal environment early
in life through exposure to endocrine disruptors can predispose us to an increased risk of developing these diseases in adulthood or with aging."

Hormone experts: Chemicals should be considered dangerous until proven safe

"Although much recent attention has focused on BPA, I don't think we can stop there," said Gore, who is researching the endocrine-disrupting properties of polychlorinated biphenyls (PCBs), industrial chemicals banned in 1977 but still detectable in most people and wildlife. "We need to learn from BPA, PCBs and other endocrine disruptors such as pesticides, fungicides, plastics and plasticizers that we cannot assume that a product
is safe until it is proven otherwise."

Among the Endocrine Society's recommendations: reverse current U.S. policy and treat that chemical compounds as potentially hazardous until shown to be safe. "This is a complete philosophical shift," said Gore, "and one that will require cooperation among individual researchers, clinicians, scientific societies and policy makers."

But as scientists implicate BPA in a lengthening roster of ailments -- among them, cancer, reproductive and cardiovascular system disorders, brain and neurological system dysfunctions, behavioral problems, diabetes and obesity -- they are galvanizing political and regulatory efforts to rein in environmental pollutants whose mysteries are only beginning to be unraveled.

Comments

[Lesscancer]

There is the opportunity to make changes in the choices we make to reduce the unnecessary and preventable exposures especially those exposures linked with risk to human health-

And while no easy task BPA is everywhere from the plastic in water bottles, to the lining of canned foods, drinks and baby formula containers, yet most startling it also can be found in some of the plastics dentists are now using.on our children's teeth.

We must widen our lenses and step back and ask ourselves why incidences of cancer are increasing especially with some pediatric cancers and those cancers not related to smoking. Cancer should not be an expected stage of life- we must all work towards a world of Less Cancer.

Bill Couzens Founder Less Cancer

[Pteryxx]

The third major finding presented, besides the HOXA10 methylation and the possible influence on cardiac arrhythmias, was that oral doses given to rhesus monkeys resulted in far lower blood levels than those observed in humans. That implies the exposures we're getting are as much as a thousand times greater than the exposure we think we're getting.

http://www.sciencenews.org/view/generic/id/44577/title/Science_%2B_the_Public__More_troubling_news_about_BPA

It's suggested that we're being exposed to BPA not only through water bottles and food containers, but through PVC water pipes, and possibly even environmental dust.

[LordMoon]

Lots of nice comments here. But BPA, is just one of about 80,000 common chemicals found everywhere.

Glyphosate, Atrazine, and those wonderful comericals on T.V. encouraging you to spray the living hell out of any insect or weed, that happens to rear it's ugly head on your home or lawn, no matter what the spray does to you.

My daughter and I have a deal, any time she sees a bug day or night, I'm available to take care of it. Sometimes they turn up in the most unusual places, like the spider that crawled inside of her cleaning glove.

She sleeps much better when it's over, and so do I, knowing that she and I are not inhaling any toxic fumes. Especially since children are much more vulnerable to their effects.

[MAragon]

YIKES!

[Kelly Coleman]

Very interesting and frightening.

By the way, so-called "methyl groups" are composed of one carbon atom and three hydrogen atoms.

[xtina8o4]

As soon as I read that (in the article) it confused me.. I actually tried to imagine the chemical structure and knew it was off.. I've definitely been out of school for too long..

[Pteryxx]

Interesting background reading that I stumbled across. This is one of the first, if not *the* first, papers to describe BPA as an estrogen mimic in 1993:

http://www.ncbi.nlm.nih.gov/pubmed/8504731

Researchers looking for estrogenic activity in yeast discovered their experiments were getting messed up, because the estrogen they measured wasn't coming from the yeast, but from the polycarbonate flasks the yeast grew in. Glass flasks didn't produce this mysterious contaminant. They isolated and analyzed the contaminant and found that it was bisphenol-A. Several different assays confirmed that the BPA was in fact binding to estrogen receptors, and that water from polycarbonate flasks caused estrogen-sensitive cells to grow faster in culture. This abstract is a wonderful example of scientists taking a weird, unexpected happening - an "anecdote" if you will - and replicating it, testing it, and finding its cause. After this paper was published, other labs began looking for BPA's effects in their own experiments and in the environment.

The last sentences:

"Our findings raise the possibility that unsuspected estrogenic activity in the form of BPA may have an impact on experiments employing media autoclaved in polycarbonate flasks. It remains to be determined whether BPA derived from consumer products manufactured from polycarbonate could significantly contribute to the pool of estrogenic substances in the environment."

[roudy]

The more we can impair the fertility of the human race the better.

[bcw]

I kind of had a similar thought. It's not as if the earth were running out of people.

[kapalabhati]

Am I a bad person that I thought this, too?

[jeanruss]

Does everyone really think this is an unknown side effect? These chemical assaults are deliberate and malevolent actions by corporations and the governments they control to play God.

[kkdc]

It's not just fertility that is affected however. The disregulation of our own hormones, by synthetic hormonal mimicry can also switch on genes that have some people at higher risk for cancer. ....and you might be a bad person that you thought that too. :)

[beyondliberal]

Ever since the media hinted of BPA's toxicity, I have firmly believed that it is responsible for the stratospheric rise in autism.
In 1981, the year my son was born, autism was considered to be a relatively rare condition, and I saw little of it in my practice. At the time, BPA was not used in baby bottles.
Once those clear bottles started showing up, I began to see a dramatic rise in language and speech-delayed children whose diagnosis was due to autism spectrum disorders. The kids began developing normally, but regressed to non-verbal functioning at between 18 months and age three. Today, ASD are diagnosed even younger, with signs showing up as young as six months of age.
What's different? BPA, that's what.

[kesmarn]

Did you notice a much lower incidence of autism in children who were beast-fed? I would think that this would be a strong indicator that your theory is correct. Of course, even mothers who breast feed sometimes supplement with water/juice/formula in bottles, but even with that, the level of exposure to BPA is bound to be much lower. I'd be interested in hearing your thoughts.

[kesmarn]

How embarrassing! "Beast-fed!!?" Of course, I meant "breast-fed!"

[Pteryxx]

Breast-feeding might not make a clear difference in infants' exposure to BPA, because BPA is already present in 90% of adults and is excreted in breast milk. How much BPA leaches out of a bottle depends on whether it has hot or boiling liquid in it, acidic juices, or certain detergents, how old the bottle is, and whether it's been exposed to sunlight... it's not a simple bottle / no bottle distinction.

I hope the EARLI study also looks at BPA in relation to autism, though; because until then we still just have an unproven, possibly coincidental correlation.

[kkdc]

And not just BPA, but also teflon, flame retardants, aluminum exposure..now used in vaccines instead of mercury. Recent article by Dr Karp at UCLA, see this same section June 30, there's a promising theory and research being done, on the "masculization" of the infant brain being caused by environmental estrogens. While these estrogens would be expected to feminize the body, in the developing fetus, it has the opposite effect.

[moonflowerjewelry]

people can dispute the findings all they want. but, just like a noticeable change in the climate in the last 20 years, to my mind there has been a noticeable change in the rates of cancer...
my cancer theory is not proveable, but just as an aside,
I went rather many years never having contact with someone whose life was touched by cancer- either their own or that of a friend or family member. in the last six years: my elderly mother and father, a customer, the friend of an acquaintance, the husband of a friend, a boy at my son's high school, my boss, and at least two women at my friday's farmers market
I am 42, and in all the years prior, there was one person I had contact with who had cancer
Not scientific, but significant

[IUAlumna]

There is a good reason why this is anecdotal, not scientific. As you age you are more likely to know people whose age makes them more susceptible to some cancers, or parents whose children suffer from cancers more common among the young. This doesn't mean cancer isn't more prevalent, it just means individual experience doesn't prove the case.

[kkdc]

The rise in cancer is associated with the Pandemic of Vitamin D deficiency. Also, our exposure to environmental pollutants.

[smileatfear]

People used to laugh at me for not microwaving my food in plastic but I had a neurobiologist explain to me exactly what happens when food (or water) is heated in plastic and it isn't pretty. I'm always careful anytime plastic or any petroleum based product is involved. No milk in plastic jugs because I can taste the plastic.

[thinkagain2]

I wonder about coffee in styrofoam cups. Always tastes bad. Gees, we have been so stupid.

[kkdc]

Styrofoam is a very unstable compound and outgases. You can taste it.

[CvillePatrick]

Interesting point. Perhaps the author of this column will comment? Is there research that addresses increased risk from heating plastic that contains BPA? Obviously there is the microwave angle. But what about the heat that most products are exposed to when being transported from factory to market? The thing with plastic (although all of it does not contain BPA) is that it is in so much these days--including the lining of most cans. [Stores now sell frozen vegetables in plastic bags that are designed to be microwaved.]

Also: at some point last year I listened to an interview on NPR's Fresh Air that dealt somewhat with international health issues. During the program the interviewee noted that the UK (for example) has been much quicker to ban questionable substances than the US. He speculated that one reason may be that it is in the best interests of that nation economically to err on the side of caution with such things because preventing illness saves the government money (because healthcare is paid for by the government). Thus, the "economic interests" of the government is likely to trump the "economic interests" of corporations. I thought the economics angle was rather interesting.]

[NMCD]

The theory is that heating plastic containers over a prolonged period means that more traces of BPA can transfer to foods and beverages stored in them. Of course the more fundamental question is whether orally ingested BPA is problematic for human beings in the first place. We don't actually have any primate studies that look at the effects of orally ingested BPA - only one from Yale in which it was subcutaneously injected.

It's true that the precautionary principle is enshrined in law and that EU regulators are much quicker to step in when there is evidence of a problem. Isn't it striking then, that the European Food Safety Authority considers BPA so safe that they actually raised the allowable daily intake last summer?

The key factor that has informed the EU's outlook is the poor quality of the studies supposedly showing low dose effects both in terms of the way the studies themselves have been conducted but also in terms of their relevancy for human beings since there are profound differences in the ability of primates to metabolize BPA as compared to rodents.

Stepping back, we might more productively ask might be what is it about North Americans and their politicians that seems to predispose them to see demons oozing from their water bottles and conspiracies at every turn?

[Pteryxx]

"Is there research that addresses increased risk from heating plastic that contains BPA?"

Yep.

http://www.ncbi.nlm.nih.gov/pubmed/18155859

"BPA was found to migrate from polycarbonate water bottles at rates ranging from 0.20 ng/h to 0.79 ng/h. At room temperature the migration of BPA was independent of whether or not the bottle had been previously used. Exposure to boiling water (100 degrees C) increased the rate of BPA migration by up to 55-fold."

"Risk" in this study was scored by toxicity of the BPA-laced water to neurons in cell culture. Another study showed increased leaching of BPA from baby bottles at 70 degrees C.

[historymatters]

chilling.

On the bright side, maybe increased infertility among humans will do something about one of those other big problems we're facing - populations growing too fast to be sustained by the local environment.

[smileatfear]

The problem isn't just infertility, it's the cancers and other devastating illnesses that BPA is suspected of causing. Every infertile couple, every cancer victim, every person developing a chronic progressive disease suffers tremedously, as does their family and friends. Please don't be glib.

[NMCD]

That's a cherry thought.

[donahue]

European is correct, a methyl group consists of a single carbon atom and three hydrogen atoms, but perhaps a "so-called" methyl group is just the opposite. Like a "so-called" editor.

[sabredance]

I'll second your correction. And I have multiple science degrees. I really hate it when the science reporters make this kind of goof, which seriously undermines their credibility for anyone in the know, a particularly troublesome mistake when the subject matter (toxicity) is so serious.

BTW we really should wait for the peer-reviewed article. How many scientific 'facts' have vanished before the lens of critical review? Remember HRT (hormone replacement therapy)? While I prefer not to drink out of plastic bottles anyway, the media is astonishing in its ability to hype something completely out of proportion.

That having been said, perhaps the BPA people are on to something real -- as in effecting real human biology and health. If so, then perhaps the gullible public will actually stop drinking bottled water, 'because it's good for you.' Never has been. More pollutants in bottled water than come out of your tap (most places in the US). More pollution, waste, and global warming from plastic bottled beverages. And bottled water is ridiculously expensive. So what you have is the perfect product: toxic to people and the environment, wasteful, expensive, but perceived as good. Who says there isn't evil in this world?

[marxmarv]

Retail single-serve drinks are typically provided in single-use polyethylene terephthalate bottles, not reusable polycarbonate. PET is worrisome due to phthalate leaching, which is unrelated to BPA.

I'd be interested to see actual research on the leaching rates and relative hazards of various types of plastics for food storage. Absent this, I favor non-clarified polyethylene and polypropylene containers due to their chemical simplicity.

[BunnyMama]

How about all the abnormal stuff those IVF embryos are exposed to? Those kids are gonna have problems as are their offspring.

[DrPolly]

As I understand it, one of the main flaws of this study is that rats received BPA through an injection and not by oral ingestion. The route of adminstration being one of the main issues of contention in the BPA controversy. I direct readers to the thorough 50-page report including a review of the evidence, the controversy, and the media coverage written by the Statistical Assessment Service (STATS) at George Mason University. It's worth mentioning that STATS.org is a non-partisan, non-political organization dedicated to improving the accuracy of scientific information in the public discourse. They, like much of the international scientific community, find little to be concerned about - this includes experts across Europe, Japan, and Australia. The European equivalent of the FDA, after reviewing all available evidence, actually raised the "safe" daily threshold by a factor of five - concluding that BPA is far safer than previously thought.

[Pteryxx]

But now that they've demonstrated specifically what genetic changes to look for, other BPA researchers can assess the genetic damage in cases of oral ingestion (or in the case of frogs, skin absorption). Wouldn't BPA administered by injection be functionally equivalent to that absorbed by other routes, as it isn't metabolized or detoxified?

[Guitarsandmore]

I saw a woman in the park the other day walking a beautiful Dalmatian. She told me the dog was 17 years old, she gave it only Arrowhead springwater from plastic bottles and fed it once a day purina dry dog food.

"I had another Dalmatian before this one," but I let it drink tap water and it only lived 10 years.

So there may be some health concerns over BPA but there is also some evidence that drinking tap water is far deadlier for you.

Why don't they just go back to putting bottled water in glass bottles, like they used to? I would still buy it.

[Pteryxx]

Because glass bottles are heavier, they'd cost too much to ship, people would be less likely to carry them, and the companies might get sued every time a child or sports fan threw one.

There's no reason to assume two random Dalmatians prove anything about water, any more than if one of them wore a lucky collar. Besides, you can always filter the tap water.

[smileatfear]

I didn't know Arrowhead had been around for 17 years. Wonder how long the dog would live if she only gave it Perrier.

[sabredance]

That's not evidence. That's anecdote. Read some epidemiology and statistics.