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

4-n-Nonylphenol and bisphenol A are endocrine disrupting chemicals that are mainly detoxified through glucuronidation. A factor that may modulate their glucuronidation rates is co-exposure to pharmaceuticals.

This study aimed to identify and characterize the potential metabolic interactions between 14 drugs and these two endocrine disruptors. Nonylphenol and bisphenol A were co-incubated in freshly isolated rat hepatocytes with, drugs at a high concentration.

Statistically significant metabolic inhibition of bisphenol A and nonylphenol biotransformation was observed with nine drugs (>50% inhibition by naproxen, salicylic acid, carbamazepine and mefenamic acid). Inhibition assays of UGT activity in rat liver microsomes revealed: 1) competitive inhibition by naproxen (K(i)(app) = 848.3 muM) and carbamazepine (K(i)(app) = 1023.1 muM), 2) no inhibition by salicylic acid suggesting another mechanism of inhibition.

Detoxification of nonylphenol and bisphenol A was shown to be impaired by excessive concentrations of many drugs and health risk assessment should therefore address this issue.

Reference: Verner MA, Magher T, Haddad S., High concentrations of commonly used drugs can inhibit the in vitro glucuronidation of bisphenol A and nonylphenol in rats, Xenobiotica. 2009 Nov 16.

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?

The Massachusetts Department of Public Health (DPH) is issuing a public health advisory for consumers concerning bisphenol A (BPA). BPA is present in baby products, including baby bottles and some infant formula. A number of studies in laboratory animals have raised concerns about potential health effects during fetal development and among nursing or formula-fed children who may be exposed to BPA. These effects include but are not limited to: changes in the infant’s developing nervous system, such as thyroid function and brain growth; changes in behavioral development, such as hyperactivity; and changes in the normal development of the prostate gland.  

Avoid products that may contain BPA

DPH is specifically advising parents and caretakers of children up to two years old to avoid the use of products that contain BPA for making or storing infant formula and breast milk. DPH is further advising pregnant and breastfeeding women to avoid products that may contain BPA. Current research suggests that BPA levels in newborns may be much higher than in adults. While researchers caution that more research needs to be conducted, it seems prudent to reduce exposures for pregnant and breastfeeding women to the extent possible in order to reduce levels in their newborn children. 

BPA is used as a liner in some food and beverage cans to prevent spoilage. It is used in a variety of other consumer products to enhance the structural integrity of plastic containers. Alternatives to plastic containers that have BPA as a component are available, and some are made by the same companies that produce products containing BPA. 

Recycling number 7 should be avoided to the extent possible

Transparent (clear or colored) plastic containers or baby bottles with the recycling number 7 and the letters PC, which stand for “polycarbonate” plastic, should be avoided to the extent possible. Heat can increase the release of BPA from polycarbonate plastic. Therefore, consumers should consider the following:

• Avoid heating plastic containers with the recycling number 7 and the letters PC in microwave ovens, in water on the stovetop, or by adding boiling water into them, particularly when preparing infant formula.
• Wash the containers by hand with warm water and soap, instead of in dishwashers.
• Stainless steel and glass do not contain BPA.
• Replace worn or scratched polycarbonate plastic containers, preferably with glass or stainless steel containers.
• Pregnant or breastfeeding women can eat or cook with fresh or frozen products instead of canned foods — which may contain BPA — to reduce fetal or infant exposure to BPA.

Some studies have found BPA in containers of canned liquid infant formula. Powdered formula does not appear to contain detectable levels of BPA. If special formula is required because of a medical condition, parents should not make any changes to their baby’s diet without consulting with their health care provider first. It is likely that known medical risks from discontinuing the use of special formula may be far greater than those that may result from BPA exposure from this source. The most effective means of reducing BPA exposure to infants is to breast feed. For both baby and mother, breastfeeding has many well-documented health benefits: 

• Breastfed babies have lower rates of some of the most serious chronic diseases: asthma, diabetes, and some childhood cancers.
• Breastfeeding reduces the risk and severity of infectious diseases: pneumonia, diarrhea, and ear infections.
•  Women who breastfeed have lower levels of ovarian and breast cancer, and breastfed daughters also have lower rates of breast cancer when they grow up.

FDA is currently considering scientific evidence

The federal Food and Drug Administration (FDA) is currently considering the scientific evidence related to health risks associated with BPA in foods and consumer products and is expected to determine the need for regulatory action in 2009. Current research on health effects associated with BPA exposure includes effects during fetal developmental and among infants, and children. Recent preliminary studies also suggest that BPA may interfere with the effectiveness of breast cancer chemotherapeutic drugs in cell culture, and may also be associated with diabetes and cardiovascular conditions in adults.

An educational brochure on this topic can be found at the DPH web site at: How to Protect Your Baby from BPA (Bisphenol A) (PDF) 

Reference:  Massachusetts Department of Public Health (DPH), DEVAL L. PATRICK – GOVERNOR, TIMOTHY P. MURRAY – LIEUTENANT GOVERNOR, JUDYANN BIGBY, M.D. – SECRETARY, JOHN AUERBACH – COMMISSIONER, For Immediate Release: Public Health Advisory Regarding Bisphenol A (BPA), August 03, 2009

Racial disparities in pregnancy outcome in the United States are significant, persistent and costly, but the causes are poorly understood. We propose that disproportionate exposure of African-American women to environmental endocrine disrupting compounds (EDCs) may contribute to birth outcome disparities. Marked racial segregation, as well as health behaviors associated with poverty could result in differences in exposure to particular EDCs. One EDC that has aroused concern in recent years is bisphenol-A (BPA), a widely used industrial plasticizer with known estrogenic properties.  

Published studies indicate that excessive BPA exposure is associated with reduced fetal survival, as well as reductions in maternal weight and fetal body weight. Related findings include adverse effects of BPA exposure on ovarian function, mammary gland development, earlier age of puberty onset and some metabolic parameters. However, these findings are largely limited to experimental animal studies, and need to be validated in human populations.  

Our review supports the need to move beyond the currently dominant toxicological approach to examining the effects of BPA exposure, and rely more on observational human studies and epidemiological methods. Many of the risk factors for racial disparities in pregnancy outcome are global or difficult to modify, but exposure to BPA is a potentially malleable risk factor. If BPA contributes to racial disparities in pregnancy outcome, there are important implications for prevention. It is our hope that this review will stimulate further research in this important and neglected area. 

Reference: Ranjit N, Siefert K, Padmanabhan V., Bisphenol-A and disparities in birth outcomes: a review and directions for future research, Journal of Perinatology advance online publication, 9 July 2009; doi:10.1038/jp.2009.90.