Early life exposure to BPA may affect testis function in adulthood

2010  study posted for filing

Contact: Aaron Lohr alohr@endo-society.org 240-482-1380 The Endocrine Society

Exposure to environmental levels of the industrial chemical bisphenol A, or BPA, in the womb and early life may cause long-lasting harm to testicular function, according to a new study conducted in animals. The results are being presented Monday at The Endocrine Society’s 92nd Annual Meeting in San Diego.

“We are seeing changes in the testis function of rats after exposure to BPA levels that are lower than what the Food and Drug Administration and Environmental Protection Agency consider safe exposure levels for humans,” said Benson Akingbemi, PhD, the study’s lead author and an associate professor at Auburn (Ala.) University. “This is concerning because large segments of the population, including pregnant and nursing mothers, are exposed to this chemical.”

Many hard plastic bottles and canned food liners contain BPA, as do some dental sealants. BPA acts in a similar manner as the female sex hormone estrogen and has been linked to female infertility. This chemical is present in placenta and is able to pass from a mother into her breast milk. In their study of the male, Akingbemi and colleagues saw harmful effects of BPA at the cellular level, specifically in Leydig cells. These cells in the testis secrete testosterone, the main sex hormone that supports male fertility. After birth, Leydig cells gradually acquire the capacity for testosterone secretion, Akingbemi explained.

The process of testosterone secretion was decreased in male offspring of female rats that received BPA during pregnancy and while nursing. The mothers were fed BPA in olive oil at a dose of either 2.5 or 25 micrograms of BPA per kilogram of body weight. Akingbemi said this is below the daily upper limit of safe exposure for humans, which federal guidelines currently put at 50 micrograms per kilogram of body weight. A control group of pregnant rats received olive oil without BPA. Male offspring, after weaning at 21 days of age, received no further exposure to BPA.

Using a combination of analytical methods, the investigators studied the development of Leydig cells in male offspring. The capacity for testosterone secretion was assessed at 21, 35 and 90 days of age. The amount of testosterone secreted per Leydig cell was found to be much lower in male offspring after early-life exposure to BPA than in offspring from control unexposed animals.

“Although BPA exposure stopped at 21 days of age, BPA’s effects on Leydig cells, which were seen immediately at the end of exposure and at 35 days, remained apparent until 90 days of age, when the rats reached adulthood,” Akingbemi said. “Therefore, the early life period is a sensitive window of exposure to BPA and exposure at this time may affect testis function into adulthood.”

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Funding from this study came in part from the Graduate Research Scholars Program of Alabama EPSCoR (Experimental Program to Stimulate Competitive Research), Tuscaloosa, Ala., and the National Institute of Environmental Health Sciences.

Prenatal exposure to endocrine-disrupting chemicals linked to breast cancer

2010 study for filing
Contact: Aaron Lohr
alohr@endo-society.org
240-482-1380
The Endocrine Society

A study in mice reveals that prenatal exposure to endocrine-disrupting chemicals, like bisphenol-A (BPA) and diethylstilbestrol (DES), may program a fetus for life. Therefore, adult women who were exposed prenatally to BPA or DES could be at increased risk of breast cancer, according to a new study accepted for publication in Hormones & Cancer, a journal of The Endocrine Society.

Endocrine-disrupting chemicals are substances in the environment that interfere with hormone biosynthesis, metabolism or action resulting in adverse developmental, reproductive, neurological and immune effects in both humans and wildlife. These chemicals are designed, produced and marketed largely for specific industrial purposes.

“BPA is a weak estrogen and DES is a strong estrogen, yet our study shows both have a profound effect on gene expression in the mammary gland (breast) throughout life,” said Hugh Taylor, MD, of the Yale University School of Medicine in New Haven, Conn. and lead author of the study. “All estrogens, even ‘weak’ ones can alter the development of the breast and ultimately place adult women who were exposed to them prenatally at risk of breast cancer.”

In this study, researchers treated pregnant mice with BPA or DES and then looked at the offspring as adults. When the offspring reached adulthood, their mammary glands still produced higher levels of EZH2, a protein that plays a role in the regulation of all genes. Higher EZH2 levels are associated with an increased risk of breast cancer in humans.

“We have demonstrated a novel mechanism by which endocrine-disrupting chemicals regulate developmental programming in the breast,” said Taylor. “This study generates important safety concerns about exposures to environmental endocrine disruptors such as BPA and suggests a potential need to monitor women exposed to these chemicals for the development of breast lesions as adults.”

 

 

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Other researchers working on the study include Leo Doherty, Jason Bromer, Yuping Zhou and Tamir Aldad of the Yale University School of Medicine in New Haven, Connecticut.

The article, “In Utero Exposure to Diethylstilbestrol (DES) or Bisphenol-A (BPA) Increases EZH2 Expression in the Mammary Gland: An Epigenetic Mechanism Linking Endocrine Disruptors to Breast Cancer,” has been published online and can be found at: http://www.springerlink.com/content/547256j0g02073v5/?p=286f52b5d3c94d9f8dc4546af408af89π=0.

Founded in 1916, The Endocrine Society is the world’s oldest, largest and most active organization devoted to research on hormones and the clinical practice of endocrinology. Today, The Endocrine Society’s membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 100 countries. Society members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society and the field of endocrinology, visit our site at www.endo-society.org.

BPA shown to disrupt thyroid function in pregnant animals and offspring

Contact: Aaron Lohr
alohr@endo-society.org
240-482-1380
The Endocrine Society

New study uses animal model similar to humans and shows BPA can affect thyroid function

Chevy Chase, MD –– In utero exposure to bisphenol A (BPA) can be associated with decreased thyroid function in newborn sheep, according to a recent study accepted for publication in Endocrinology, a journal of The Endocrine Society. Hypothyroidism is characterized by poor mental and physical performance in human adults and in children can result in cognitive impairment and failure to grow normally.

BPA, a major molecule used in the plastic industry, has been shown to be an endocrine disruptor that could exert deleterious effects on human health. Most investigations have focused on reproductive functions, but there is evidence that BPA might have negative effects on other endocrine systems including thyroid function. The current study used sheep, a relevant model for human pregnancy and thyroid regulation and ontogeny, and analyzed the internal exposures of the fetuses and their mothers to BPA and determined to what extent those exposures may be associated with thyroid disruption.

“Our study is the first to show that BPA can alter thyroid function of pregnant animals and their offspring in a long-gestation species with similar regulation of thyroid function as humans,” said Catherine Viguié, PhD, of Toxalim, Research Centre in Food Toxicology in Toulouse, France and lead author of the study. “Because of the potential consequences of maternal/fetal thyroid disruption on neural and cognitive development, we think that our study warrants the need for further investigations on the effect of BPA on thyroid function.”

This study was conducted on adult ewes that had multiple pregnancies before being included in the experiment. Some of the pregnant ewes received daily subcutaneous injections of BPA while the remainder were allocated to the control group. Blood samples were taken from jugular blood, amniotic fluid, placenta samples and cord blood to determine levels of BPA, thyroid-stimulating hormone (TSH) and thyroxine. Results showed that maternal and fetal exposure to BPA was associated with disruption of thyroid function of both the pregnant ewes throughout pregnancy and the newborns as characterized by a decrease in circulating thyroxine levels.

“BPA concentrations in the mother blood in this experiment were fluctuating between injections from 15 to 1 time the highest blood levels reported in pregnant women in the literature,” notes Viguié. “As a consequence, although this study clearly indicates that BPA has the potential to alter thyroid function in living pregnant animals and their offspring, it cannot be considered as fully conclusive in terms of risk for human health in the actual conditions of exposure of human populations.”

“In other words, although our study clearly indicates that BPA-induced thyroid disruption is possible, it does not indicate how probable such a disruption is to occur in real conditions,” added Viguié. “Thus, the main merit of our work is to encourage others, including epidemiologists, to scrutinize and qualify carefully such a probability.”

 

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Other researchers working on the study include: Séverine Collet, Véronique Gayrard, Nicole Picard-Hagen, Sylvie Puel, Béatrice Roques, Pierre-Louis Toutain and Marlène Lacroix of Institut National de la Recherche Agronomique (INRA), Toxalim, and the Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse in France.

The article, “Maternal and fetal exposure to bisphenol A is associated to alterations of thyroid function in pregnant ewes and their newborn lambs,” appears in the January 2013 issue of Endocrinology.

Founded in 1916, The Endocrine Society is the world’s oldest, largest and most active organization devoted to research on hormones and the clinical practice of endocrinology. Today, The Endocrine Society’s membership consists of over 15,000 scientists, physicians, educators, nurses and students in more than 100 countries. Society members represent all basic, applied and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society and the field of endocrinology, visit our site at www.endo-society.org. Follow us on Twitter at https://twitter.com/#!/EndoMedia.

Common antidepressant drugs linked to lactation difficulties in moms

2010 study posted for filing

Contact: Aaron Lohr alohr@endo-society.org 240-482-1380 The Endocrine Society

According to a new study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM), women taking commonly used forms of antidepressant drugs may experience delayed lactation after giving birth and may need additional support to achieve their breastfeeding goals.

Breastfeeding benefits both infants and mothers in many ways as breast milk is easy to digest and contains antibodies that can protect infants from bacterial and viral infections. The World Health Organization recommends that infants should be exclusively breastfed for the first six months of life. This new study shows that certain common antidepressant drugs may be linked to a common difficulty experienced by new mothers known as delayed secretory activation, defined as a delay in the initiation of full milk secretion.

“The breasts are serotonin-regulated glands, meaning the breasts’ ability to secrete milk at the right time is closely related to the body’s production and regulation of the hormone serotonin,” said Nelson Horseman, PhD, of the University of Cincinnati and co-author of the study. “Common antidepressant drugs like fluoxetine, sertraline and paroxetine are known as selective serotonin reuptake inhibitor (SSRI) drugs and while they can affect mood, emotion and sleep they may also impact serotonin regulation in the breast, placing new mothers at greater risk of a delay in the establishment of a full milk supply.”

In this study, researchers examined the effects of SSRI drugs on lactation using laboratory studies of human and animal cell lines and genetically modified mice. Furthermore, an observational study evaluated the impact of SSRI drugs on the onset of milk production in postpartum women. In this study of 431 postpartum women, median onset of lactation was 85.8 hours postpartum for the SSRI-treated mothers and 69.1 hours for mothers not treated with SSRI drugs. Researchers commonly define delayed secretory activation as occurring later than 72 hours postpartum.

“SSRI drugs are very helpful medications for many moms, so understanding and ameliorating difficulties moms experience can help them achieve their goals for breastfeeding their babies,” said Horseman. “More human research is needed before we can make specific recommendations regarding SSRI use during breastfeeding.”

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Other researchers working on the study include: Aaron Marshall, Laura Hernandez and Karen Gregerson of the University of Cincinnati in Ohio; Laurie Nommsen-Rivers of Cincinnati Children’s Hospital Medical Center in Ohio; Kathryn Dewey of the University of California at Davis; and Caroline Chantry of the University of California Davis Medical Center in Sacramento.

The article, “Serotonin transport and metabolism in the mammary gland modulates secretory activation and involution,” will appear in the February 2010 issue of JCEM.

Founded in 1916, The Endocrine Society is the world’s oldest, largest and most active organization devoted to research on hormones and the clinical practice of endocrinology. Today, The Endocrine Society’s membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 100 countries. Society members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society and the field of endocrinology, visit our site at www.endo-society.org.

Bisphenol A exposure in pregnant mice permanently changes DNA of offspring

2009 study posted for filing

Contact: Aaron Lohr
alohr@endo-society.org
240-482-1380
The Endocrine Society

Exposure during pregnancy to the chemical bisphenol A, or BPA, found in many common plastic household items, is known to cause a fertility defect in the mother’s offspring in animal studies, and now researchers have found how the defect occurs. The results of the new study will be presented Saturday at The Endocrine Society’s 91st Annual Meeting in Washington, D.C.

The study, funded partly by the National Institutes of Health, joins a growing body of animal research showing the toxic health effects of BPA, including reproductive and developmental problems. Last August the U.S. Food and Drug Administration found BPA to be safe as currently used but later said more research on its safety is needed. BPA is used to make hard polycarbonate plastic, such as for baby bottles, refillable water bottles and food containers, as well as to make the linings of metal food cans.

BPA has estrogen-like properties and in pregnant animals has been linked to female infertility.

“The big mystery is how does exposure to this estrogen-like substance during a brief period in pregnancy lead to a change in uterine function,” said study co-author Hugh Taylor, MD, professor and chief of the reproductive endocrinology section at Yale University School of Medicine.

To find the answer to that question, Taylor and his co-workers at Yale injected pregnant mice with a low dose of BPA on pregnancy days 9 to 16. After the mice gave birth, the scientists analyzed the uterus of female offspring and extracted DNA.

They found that BPA exposure during pregnancy had a lasting effect on one of the genes that is responsible for uterine development and subsequent fertility in both mice and humans (HOXA10). Furthermore, these changes in the offspring’s uterine DNA resulted in a permanent increase in estrogen sensitivity. The authors believe that this process causes the overexpression of the HOXA10 gene in adult mice that they found in previous studies.

The permanent DNA changes in the BPA-exposed offspring were not apparent in the offspring of mice that did not receive BPA injection (the controls). This finding demonstrates that the fetus is sensitive to BPA in mice and likely also in humans, Taylor said.

“We don’t know what a safe level of BPA is, so pregnant women should avoid BPA exposure,” Taylor said. “There is nothing to lose by avoiding items made with BPA—and maybe a lot to gain.”

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Gestational exposure to urban air pollution linked to vitamin D deficiency in newborns

Contact: Aaron Lohr alohr@endo-society.org 240-482-1380 The Endocrine Society

New study highlights potential importance of vitamin D supplementation in pregnant women

Chevy Chase, MD—Gestational exposure to ambient urban air pollution, especially during late pregnancy, may contribute to lower vitamin D levels in offspring, according to a recent study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology and Metabolism (JCEM). According to study authors, this could affect the child’s risk of developing diseases later in life.

Recent data have demonstrated that maternal vitamin D deficiency during pregnancy may have an influence on the development of asthma and allergic diseases in offspring. A number of factors may influence vitamin D supply in women. Exposure to high levels of air pollution has been suggested as a contributor to vitamin D deficiency in adults and children.

“We investigated the associations between gestational exposure to urban air pollutants and vitamin D cord blood serum level,” said Nour Baïz, MASc, of Intitut National de la Santé et de la Recherche Médicale (INSERM) in Paris, France who led the study. “Our findings show for the first time, that exposure to ambient air pollution comparable to current World Health Organization standards might contribute to vitamin D deficiency in newborns.”

In this study, researchers investigated the associations between gestational exposure to urban air pollutants and 25-hydroxyvitamin D cord blood serum level in 375 mother-child pairs. Maternal exposure to urban levels of nitrogen dioxide and particulate matter less than 10 micro meters during the whole pregnancy was a strong predictor of low vitamin D status in newborns. The association between gestational exposure to air pollutants and vitamin D deficiency in newborns was strongest for third-trimester exposures.

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Other researchers participating in the study included: Isabella Annesi-Maesano of INSERM; Patricia Dargent-Molina of University Pierre and Marie Curie in Paris, France; John Wark of The Royal Melbourne Hospital in Victoria, Australia; Jean-Claude Souberbielle of Université Paris-Descartes in Paris, France; and Rémy Slama of Institut Albert Bonniot in Grenoble, France.

The article “Gestational Exposure to Urban Air Pollution Related to a Decrease in Cord Blood Vitamin D Levels” is slated to appear in the November 2012 issue of JCEM.

Founded in 1916, The Endocrine Society is the world’s oldest, largest and most active organization devoted to research on hormones and the clinical practice of endocrinology.  Today, The Endocrine Society’s membership consists of over 15,000 scientists, physicians, educators, nurses and students in more than 100 countries. Society members represent all basic, applied and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society and the field of endocrinology, visit our site at www.endo-society.org. Follow us on Twitter at https://twitter.com/#!/EndoMedia.

High-fructose corn syrup sugar makes maturing human fat cells fatter, less insulin-sensitive

Contact: Aaron Lohr alohr@endo-society.org 240-482-1380 The Endocrine Society

Fructose, the sugar widely used as high-fructose corn syrup in soft drinks and processed foods, often gets some of the blame for the widespread rise in obesity. Now a laboratory study has found that when fructose is present as children’s fat cells mature, it makes more of these cells mature into fat cells in belly fat and less able to respond to insulin in both belly fat and fat located below the skin.

The results will be presented Sunday at The Endocrine Society’s 92nd Annual Meeting in San Diego by lead author Georgina Coade, a PhD student at the University of Bristol in the U.K.

“Our results suggest that high levels of fructose, which may result from eating a diet high in fructose, throughout childhood may lead to an increase in visceral [abdominal] obesity, which is associated with increased cardiometabolic risk,” Coade said.

Defined by a large waistline, abdominal obesity raises the risk of heart disease and Type 2 diabetes. The abdominal cavity contains one of two major types of fat in the body: visceral fat. The other type, subcutaneous fat, is found below the surface of the skin.

Although researchers have shown the negative effects of fructose on the fat distribution of rodents, the effects of this sugar on human adipocytes, or fat cells, are not clear, according to Coade. Therefore, she and her fellow researchers studied biopsy specimens of both subcutaneous and visceral fat from 32 healthy-weight children who had not yet gone through puberty.

From the biopsy samples, the investigators obtained preadipocytes—the precursors to fat cells that have the potential to differentiate, or mature, into fat-containing adipocytes. They then allowed the precursor cells to mature for 14 days in culture media containing normal glucose (the main sugar found in the bloodstream and the principal source of energy in the body), high glucose or high fructose. The researchers assessed cell differentiation by measuring activity of an enzyme (GPDH) and the abundance of the adipocyte fatty acid binding protein, which are both present only in mature fat cells.

Fructose, the research team found, had different effects to that of glucose and caused the fat cells to differentiate more—that is, to form more mature fat cells—but only in visceral fat.

For both types of fat cells, maturation in fructose decreased the cells’ insulin sensitivity, which is the ability to successfully take up glucose from the bloodstream into fat and muscles. Decreased insulin sensitivity is a characteristic of Type 2 diabetes.

Although prolonged exposure to fructose had a negative effect on insulin sensitivity, when Coade and her co-workers exposed mature fat cells, rather than preadipocytes, to fructose for 48 hours, the cells’ insulin sensitivity increased. The reason why is unknown. However, she said, “Fructose alters the behavior of human fat cells if it is present as the fat cells mature. We can maybe compare this [timing] to periods in children when they are making their fat.”

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The London-based organization Diabetes UK helped fund this study.

BPA exposure in utero may increase predisposition to breast cancer

Contact: Aaron Lohr alohr@endo-society.org 240-482-1380 The Endocrine Society

Study finds perinatal exposure to BPA has effect on mammary hormone response

Chevy Chase, MD—A recent study accepted for publication in Molecular Endocrinology, a journal of The Endocrine Society, found that perinatal exposure to environmentally relevant doses of bisphenol A (BPA) alters long-term hormone response and breast development in mice that may increase the propensity to develop cancer.

BPA, a man-made chemical produced and marketed largely for specific industrial purposes, is detected in body fluids of more than 90 percent of the human population. It was originally synthesized as an estrogenic compound and there has been concern that exposure to BPA could have developmental effects on various hormone-responsive organs including the mammary gland.

“I want it to be clear that we do not provide evidence that BPA exposure causes breast cancer per se,” said Cathrin Brisken, MD, of the Swiss Institute for Experimental Cancer Research and co-author of the study. “We do provide evidence that BPA exposure alters mammary gland development and that this may increase the predisposition of the breast to breast cancer.”

In this study, researchers mimicked human exposure to BPA as it occurs with beverages and food from BPA containing vessels (such as plastics and the lining of tin cans) by adding the compound to the drinking water of breeding mice. Female pups born from BPA-consuming parents were transferred to a BPA-free environment at weaning and followed over time.

Researchers analyzed changes in the mammary gland of female offspring that were exposed to BPA through their mothers in utero and while being breast fed. The mammary glands of BPA exposed females showed an increased response to the hormone progesterone. Lifetime exposure to progesterone has been linked to increase breast cancer risk.

Furthermore, researchers  found that adult females who had been exposed to BPA in utero and while breast fed, showed a 1.5 fold increase in cell numbers in their milk ducts. This is comparable to what is seen upon similar exposure to another estrogenic compound, diethyllbestrol (DES). Uterine exposure to DES in the human population has been shown to increase the relative risk of getting breast cancer two-fold as women reach their fifties.

“While we cannot extrapolate these results directly from mice to humans, the possibility that some of the increase in breast cancer incidence observed over the past decades may be attributed to exposure to BPA cannot be dismissed,” said Brisken. “Our study suggests that pregnant and breastfeeding mothers should avoid exposure to BPA as it may affect their daughters’ breast tissue.”

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Other researchers working on the study include Ayyakkannu Ayyanan, Ouahiba Laribi, Sonia Schuepbach-Mallepell, Christina Schrick, Maria Gutierrez, Tamara Tanos and Ozden Yalcin-Ozuysal of the Swiss Institute for Experimental Cancer Research; and Gregory Lefebvre and Jacques Rougemont of École polytechnique fédérale de Lausanne in Switzerland.

The article, “Perinatal exposure to bisphenol A increases adult mammary gland progesterone response and cell number,” appears in the November 2011 issue of Molecular Endocrinology.

Founded in 1916, The Endocrine Society is the world’s oldest, largest and most active organization devoted to research on hormones and the clinical practice of endocrinology.  Today, The Endocrine Society’s membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 100 countries. Society members represent all basic, applied and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society and the field of endocrinology, visit our site at www.endo-society.org.