Yale scientists show how bisphenol A induces epigenetic changes in pregnant mice that cause hormonal imbalance in the later life of female progeny

Here’s more evidence that “safe” plastics are not as safe as once presumed: New research published online in The FASEB Journal suggests that exposure to Bisphenol A (BPA) during pregnancy leads to epigenetic changes that may cause permanent reproduction problems for female offspring. BPA, a common component of plastics used to contain food, is a type of estrogen that is ubiquitous in the environment.

“Exposure to BPA may be harmful during pregnancy; this exposure may permanently affect the fetus,” said Hugh S. Taylor, Ph.D., co-author of the study from Yale University School of Medicine in New Haven, Connecticut. “We need to better identify the effects of environmental contaminants on not just crude measures such as birth defects, but also their effect in causing more subtle developmental errors.”

Taylor and colleagues made this discovery by exposing fetal mice to BPA during pregnancy and examining gene expression and DNA in the uteruses of female fetuses. Results showed that BPA exposure permanently affected the uterus by decreasing regulation of gene expression. These epigenetic changes caused the mice to over-respond to estrogen throughout adulthood, long after the BPA exposure. This suggests that early exposure to BPA genetically “programmed” the uterus to be hyper-responsive to estrogen. Extreme estrogen sensitivity can lead to fertility problems, advanced puberty, altered mammary development and reproductive function, as well as a variety of hormone-related cancers. BPA has been widely used in plastics and other materials. Examples include use in water bottles, baby bottles, epoxy resins used to coat food cans, and dental sealants.

“The BPA baby bottle scare may be only the tip of the iceberg.” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “Remember how diethylstilbestrol (DES) caused birth defects and cancers in young women whose mothers were given such hormones during pregnancy. We’d better watch out for BPA, which seems to carry similar epigenetic risks across the generations. ”

Author: FASEB* – Federation of American Societies for Experimental Biology, Why BPA leached from ’safe’ plastics may damage health of female offspring, 25-Feb-2010.

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* FASEB comprises 23 societies with more than 90,000 members, making it the largest coalition of biomedical research associations in the United States

A new study led by Mount Sinai researchers in collaboration with scientists from Cornell University and the U.S. Centers for Disease Control and Prevention, has found higher prenatal exposure to phthalates—manmade chemicals that interfere with hormonal messaging—to be connected with disruptive and problem behaviors in children between the ages of 4 and 9 years. The study, which is the first to examine the effects of prenatal phthalate exposure on child neurobehavioral development, will be published January 28, on the Environmental Health Perspectives website.

“There is increasing evidence that phthalate exposure is harmful to children at all stages of development,” said Stephanie Engel, PhD, lead study author and Associate Professor of Preventive Medicine at Mount Sinai School of Medicine. “We found a striking pattern of associations between low molecular weight phthalates – which are commonly found in personal care products – and disruptive childhood behaviors, such as aggressiveness and other conduct issues, and problems with attention. These same behavioral problems are commonly found in children diagnosed with Attention-Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder, or Conduct Disorder.”

Phthalates are part of a group of chemicals known as endocrine disruptors, that interfere with the body’s endocrine, or hormone system. They are a family of compounds found in a wide range of consumer products such as nail polishes, to increase their durability and reduce chips, and in cosmetics, perfumes, lotions and shampoos, to carry fragrance. Other phthalates are used to increase the flexibility and durability of plastics such as PVC, or included as coatings on medications or nutritional supplements to make them timed-release.

“Recently, the government instituted regulations limiting certain phthalates in things like child care articles or toys that a young child might put in their mouth,” continued Dr. Engel. “But it’s their mother’s contact with phthalate-containing products that causes prenatal exposure. The phthalates that we found most strongly related to neurodevelopment were those commonly found in cosmetics, perfumes, lotions and shampoos. Current US regulations do not address these kinds of phthalates.”

For the study, phthalate metabolite levels were analyzed in prenatal urine samples of a multiethnic group of 404 women who were pregnant for the first time. The women were invited to participate in follow-up interviews when their children were between the ages of 4 and 9. The mothers were not informed of their phthalate metabolite levels and the researchers were unaware of their exposures when testing the children.

Follow-up visits were completed by 188 of the women and their children. At each follow-up visit, the mothers completed validated questionnaires designed to assess their behavior and executive functions. The researchers found that mothers with higher concentrations of low molecular weight phthalates consistently reported poorer behavioral profiles in their children. The strongest trends were in the categories of conduct and externalizing problems, characteristics typically associated with Oppositional Defiant Disorder, Conduct Disorder and ADHD.

“These are high level, chronic exposures that start before the child is even born, but continue throughout their life. More research is needed to examine the effects of cumulative exposure to phthalates on child development. But what this study suggests is that it’s not enough to regulate childhood exposure to these chemicals. The regulations need to include products that moms use,” said Dr. Engel.

Reference: The Mount Sinai Hospital / Mount Sinai School of Medicine, Mount Sinai finds prenatal exposure to certain chemicals affects childhood neurodevelopment, Jan. 28, 2010

Male reproductive disorders that are of interest from an environmental point of view include sexual dysfunction, infertility, cryptorchidism, hypospadias and testicular cancer.

Several reports suggest declining sperm counts and increase of these reproductive disorders in some areas during some time periods past 50 years. Except for testicular cancer this evidence is circumstantial and needs cautious interpretation. However, the male germ line is one of the most sensitive tissues to the damaging effects of ionizing radiation, radiant heat and a number of known toxicants.

So far occupational hazards are the best documented risk factors for impaired male reproductive function and include physical exposures (radiant heat, ionizing radiation, high frequency electromagnetic radiation), chemical exposures (some solvents as carbon disulfide and ethylene glycol ethers, some pesticides as dibromochloropropane, ethylendibromide and DDT/DDE, some heavy metals as inorganic lead and mercury) and work processes such as metal welding. Improved working conditions in affluent countries have dramatically decreased known hazardous workplace exposures, but millions of workers in less affluent countries are at risk from reproductive toxicants. New data show that environmental low-level exposure to biopersistent pollutants in the diet may pose a risk to people in all parts of the world.

For other noxicants the evidence is only suggestive and further evaluation is needed before conclusions can be drawn. Whether compounds as phthalates, bisphenol A and boron that are present in a large number of industrial and consumer products entails a risk remains to be established. The same applies to psychosocial stressors and use of mobile phones.

Finally, there are data indicating a particular vulnerability of the fetal testis to toxicants – for instance maternal tobacco smoking. Time has come where male reproductive toxicity should be addressed form entirely new angles including exposures very early in life.

Literatur:
Bonde JP., Male reproductive organs are at risk from environmental hazards, Department of Occupational and Environmental Medicine, Bispebjerg University Hospital, Copenhagen, Denmark, Asian J Androl. 2009 Dec 7.

If it hadn’t been for the Big Macs that Joannie ate pretty much three times a week, she wouldn’t have gotten fat.  If she hadn’t been exposed while in her mother’s womb to chemicals x, y and z, Joannie wouldn’t have had the propensity to get fat.  And if Joannie’s mom had eaten more sensibly, both waistlines would be slimmer.

Fat people most likely are programmed to become fat before taking their first sip of milk.

Today’s news is, that pesticides are among the chemicals responsible for this reprogramming.

Two of three U.S. adults are now classified as overweight.  Type II diabetes has increased in like measure over the same decades, and so has heart disease.  This is not a coincidence.  These illnesses share common characteristics: they are triggered while in the womb by exposure to the same kinds of chemicals and the outcomes show up in adulthood.  Scientists now call this pattern “the fetal origins of adult diseases”.

The most likely culprits are chemicals now grouped together under the rubric “endocrine disrupters.” It’s been known for about two decades, though disputed by the manufacturers, that these chemicals alter the normal signaling pathways of hormones.  Think of Bisphenol A (BPA), right now the nation’s most celebrated endocrine disruptor.

Pesticides, though not specifically thought of as endocrine disruptors nor regulated as such, can similarly knock normal development off track.  Research has just found that a family of pesticides among the most widely used in the world is connected to these three adult illnesses.  This is the family of organophosphates, concocted from petroleum with an addition of phosphoric acid.

When lab rats are exposed to these pesticides through the mother’s diet, at a time in their development equivalent to a human baby’s second trimester in the womb, their metabolism changes in two ways: their cholesterol and triglycerides rise.  These abnormal and lasting changes resemble the major factors that predict and lead, later in life, to obesity, diabetes and cardiovascular heart disease (specifically, atherosclerosis, a condition in which fatty material collects along the arteries and hardens artery walls).

These changes in metabolism happen at low levels, within the levels we are uniformly exposed to, which the Environmental Protection Agency declares as “safe” but are evidently not.  The changes are the strongest when the mother rats are fed a high-fat diet.  Human babies may even be underweight at birth (and there’s an epidemic of underweight babies in the U.S.), but quickly become overweight

Humans run into these pesticides in our food and water.  Of course, children continue to be exposed once they are born and are in fact exposed more than adults because they eat and drink more in relation to their body weight and have a higher ratio of skin.

The other groups of people exposed most to organophosphates and other pesticides are the same groups with the highest rates of obesity – people who live in run-down inner-city neighborhoods, the poor, and farmworkers.  Again, not a coincidence but a connection, a trigger.

Dr. Ted Slotkin of Duke University, the researcher responsible for these discoveries, found another compelling clue: exposure caused harm to the rodent’s brain, as well as its metabolism.  Once the exposed lab animal was born and started to eat at will, its consumption of a high-fat diet reduced the adverse symptoms in its brain functioning.  As Dr. Slotkin muses, “If you’ve got neurofunctional deficits, and they can be offset by continually eating Big Macs, then you will naturally (but unconsciously) select that kind of food because it will make you feel better.”  Unfortunately, increased fat will further harm the animal’s, or human’s, metabolism.

What this means for you:

Particularly while trying to conceive, during pregnancy, while nursing, and for your children, avoid pesticides; eat organic foods.

For information about endocrine disruptors, read the new booklet published by the nonprofit Learning and Developmental Disabilities Initiative.

Author: Alice Shabecoff for CSN – Chemical Sensitivity Network, November 5, 2009

Alice Shabecoff is the co-author with her husband Philip of Poisoned Profits: The Toxic Assault on our Children, published by Random House last year.  See their website, www.poisonedprofits.com

Related article from Alice Shabecoff:

• Our planet, our children – How are your children doing?

WASHINGTON – The U.S. Environmental Protection Agency today released a user-friendly document to help risk assessors understand how children are exposed to pollution. The document, titled “Highlights of the Child-Specific Exposure Factors Handbook” serves as a quick-reference guide to the more comprehensive “Child-Specific Exposure Factors Handbook” published by EPA in 2008. It will serve as an additional resource for those who work on children’s health issues, which the agency has been highlighting during Children’s Health Month.

EPA developed the reference guide to provide important information necessary for answering questions about exposure through drinking water, breathing, and eating foods, such as:

• How much exposure to environmental pollutants might children get if they live or play near contaminated sites?
• How much dirt from a child’s hands might s/he inadvertently eat?
• How much of a child’s exposure to various pollutants might come from skin contact?
• Which age groups (childhood life stages) may inhale or ingest the most and thus may be at higher risks?

More information on the documents:

• http://www.epa.gov/childexpfactors/highlights
• http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=200445

Reference: EPA Releases Guide to Help Scientists Understand Children’s Exposure to Pollutants, Release date: 10/27/2009