Of endocrine disruptors and pregnancy

There are no randomized controlled trials in which pregnant women in one group are exposed to endocrine-disrupting chemicals while a similar control group is protected from the same chemicals. It’s ethically impossible.

Still, evidence is mounting of the potential harm to fetuses from environmental exposure to bisphenol A (BPA) and other endocrine disruptors in human case-control and epidemiological studies, as well as in studies of animals or human cells. BPA is a synthetic estrogen used in carbonless receipts, plastic bottles, food-can liners, and more.

At the Endocrine Society’s Annual Meeting, a French study linked BPA exposure to higher risk for male babies to be born with undescended testicles. Investigators in Chicago grafted human prostate stem cells into mice and showed that exposure to BPA while tissues are developing produced greater risk for prostate cancer later in life. Building on prior human epidemiological studies suggesting that BPA exposure is associated with risk for metabolic syndrome, a study of pregnant sheep found that fetal exposure to BPA increased inflammation in fat tissue after birth, which can lead to obesity and metabolic syndrome.

The findings are "striking" in that they each connect fetal exposure to BPA with later development of disease, said Dr. Joanna Spencer-Segal of the University of Michigan, Ann Arbor, who moderated a press briefing on endocrine disruptors.

Dr. Patrick Fénichel and his associates screened all 6,246 boys born at one hospital after 34 weeks’ gestation and matched two normal male newborns with each of the 52 born with isolated cryptochordism. Umbilical cord blood assays showed that infants with cryptochordism had significantly lower levels of insulin-like peptide 3 (INSL-3), one of two hormones that regulate testicular descent. Blood levels of BPA were inversely correlated with INSL-3 levels – the more BPA on board, the lower the level of the hormone, said Dr. Fénichel, professor and head of the endocrinology department at the University Hospital, Nice, France.

Gail S. Prins, Ph.D. and her associates took the mice with human prostate stem cells and gave them BPA in levels found in humans for 2 weeks. When the prostate tissue had matured a month after grafting, they gave the mice estrogen and testosterone to mimic hormonal changes in aging men. Over the next 4 months, 33%-45% of the 27 mice exposed to varying amounts of BPA developed high-grade prostate intraepithelial neoplasia or prostate adenocarcinoma, compared with 12% of the 34 control mice, said Dr. Prins, professor of urology at the University of Illinois, Chicago.

Almudena Veiga-Lopez, D.V.M., Ph.D., and her associates randomized 12 pregnant sheep to be fed corn oil with or without BPA, and studied their 33 offspring. In each group, they overfed half of the offspring to make them obese. At 15 months of age, fat tissue in the obese sheep had abnormal levels of two markers of inflammation – CD68 and adiponectin – and the CD68 levels also were abnormal in normal-weight female offspring of mother sheep who had been fed BPA, reported Dr. Veiga-Lopez, also of the University of Michigan. Tissue inflammation can be a precursor to metabolic diseases such as obesity, diabetes, or cardiovascular disease, she pointed out.

These are hardly the first studies to trigger alarm about BPA and similar chemicals. Our report from the Endocrine Society’s 2012 meeting highlighted studies showing that children’s weight correlated with their blood levels of another endocrine disruptor, di(2-ethylhexyl)phthalate, and that prenatal exposure to a mixture of endocrine disruptors caused long-term adverse changes in the developing brains of rats.

There’s no easy way to avoid all of these chemicals at the moment, though pregnant women should try, the speakers said. What are really needed are tougher international regulations requiring industry to test new chemicals for safety before introducing them to the market, Dr. Prins said.

All speakers reported having no financial disclosures.

–By Sherry Boschert

[email protected]

On Twitter @sherryboschert

There are no randomized controlled trials in which pregnant women in one group are exposed to endocrine-disrupting chemicals while a similar control group is protected from the same chemicals. It’s ethically impossible.

Still, evidence is mounting of the potential harm to fetuses from environmental exposure to bisphenol A (BPA) and other endocrine disruptors in human case-control and epidemiological studies, as well as in studies of animals or human cells. BPA is a synthetic estrogen used in carbonless receipts, plastic bottles, food-can liners, and more.

At the Endocrine Society’s Annual Meeting, a French study linked BPA exposure to higher risk for male babies to be born with undescended testicles. Investigators in Chicago grafted human prostate stem cells into mice and showed that exposure to BPA while tissues are developing produced greater risk for prostate cancer later in life. Building on prior human epidemiological studies suggesting that BPA exposure is associated with risk for metabolic syndrome, a study of pregnant sheep found that fetal exposure to BPA increased inflammation in fat tissue after birth, which can lead to obesity and metabolic syndrome.

The findings are "striking" in that they each connect fetal exposure to BPA with later development of disease, said Dr. Joanna Spencer-Segal of the University of Michigan, Ann Arbor, who moderated a press briefing on endocrine disruptors.

Dr. Patrick Fénichel and his associates screened all 6,246 boys born at one hospital after 34 weeks’ gestation and matched two normal male newborns with each of the 52 born with isolated cryptochordism. Umbilical cord blood assays showed that infants with cryptochordism had significantly lower levels of insulin-like peptide 3 (INSL-3), one of two hormones that regulate testicular descent. Blood levels of BPA were inversely correlated with INSL-3 levels – the more BPA on board, the lower the level of the hormone, said Dr. Fénichel, professor and head of the endocrinology department at the University Hospital, Nice, France.

Gail S. Prins, Ph.D. and her associates took the mice with human prostate stem cells and gave them BPA in levels found in humans for 2 weeks. When the prostate tissue had matured a month after grafting, they gave the mice estrogen and testosterone to mimic hormonal changes in aging men. Over the next 4 months, 33%-45% of the 27 mice exposed to varying amounts of BPA developed high-grade prostate intraepithelial neoplasia or prostate adenocarcinoma, compared with 12% of the 34 control mice, said Dr. Prins, professor of urology at the University of Illinois, Chicago.

Almudena Veiga-Lopez, D.V.M., Ph.D., and her associates randomized 12 pregnant sheep to be fed corn oil with or without BPA, and studied their 33 offspring. In each group, they overfed half of the offspring to make them obese. At 15 months of age, fat tissue in the obese sheep had abnormal levels of two markers of inflammation – CD68 and adiponectin – and the CD68 levels also were abnormal in normal-weight female offspring of mother sheep who had been fed BPA, reported Dr. Veiga-Lopez, also of the University of Michigan. Tissue inflammation can be a precursor to metabolic diseases such as obesity, diabetes, or cardiovascular disease, she pointed out.

These are hardly the first studies to trigger alarm about BPA and similar chemicals. Our report from the Endocrine Society’s 2012 meeting highlighted studies showing that children’s weight correlated with their blood levels of another endocrine disruptor, di(2-ethylhexyl)phthalate, and that prenatal exposure to a mixture of endocrine disruptors caused long-term adverse changes in the developing brains of rats.

There’s no easy way to avoid all of these chemicals at the moment, though pregnant women should try, the speakers said. What are really needed are tougher international regulations requiring industry to test new chemicals for safety before introducing them to the market, Dr. Prins said.

All speakers reported having no financial disclosures.

–By Sherry Boschert

[email protected]

On Twitter @sherryboschert

There are no randomized controlled trials in which pregnant women in one group are exposed to endocrine-disrupting chemicals while a similar control group is protected from the same chemicals. It’s ethically impossible.

Still, evidence is mounting of the potential harm to fetuses from environmental exposure to bisphenol A (BPA) and other endocrine disruptors in human case-control and epidemiological studies, as well as in studies of animals or human cells. BPA is a synthetic estrogen used in carbonless receipts, plastic bottles, food-can liners, and more.

At the Endocrine Society’s Annual Meeting, a French study linked BPA exposure to higher risk for male babies to be born with undescended testicles. Investigators in Chicago grafted human prostate stem cells into mice and showed that exposure to BPA while tissues are developing produced greater risk for prostate cancer later in life. Building on prior human epidemiological studies suggesting that BPA exposure is associated with risk for metabolic syndrome, a study of pregnant sheep found that fetal exposure to BPA increased inflammation in fat tissue after birth, which can lead to obesity and metabolic syndrome.

The findings are "striking" in that they each connect fetal exposure to BPA with later development of disease, said Dr. Joanna Spencer-Segal of the University of Michigan, Ann Arbor, who moderated a press briefing on endocrine disruptors.

Dr. Patrick Fénichel and his associates screened all 6,246 boys born at one hospital after 34 weeks’ gestation and matched two normal male newborns with each of the 52 born with isolated cryptochordism. Umbilical cord blood assays showed that infants with cryptochordism had significantly lower levels of insulin-like peptide 3 (INSL-3), one of two hormones that regulate testicular descent. Blood levels of BPA were inversely correlated with INSL-3 levels – the more BPA on board, the lower the level of the hormone, said Dr. Fénichel, professor and head of the endocrinology department at the University Hospital, Nice, France.

Gail S. Prins, Ph.D. and her associates took the mice with human prostate stem cells and gave them BPA in levels found in humans for 2 weeks. When the prostate tissue had matured a month after grafting, they gave the mice estrogen and testosterone to mimic hormonal changes in aging men. Over the next 4 months, 33%-45% of the 27 mice exposed to varying amounts of BPA developed high-grade prostate intraepithelial neoplasia or prostate adenocarcinoma, compared with 12% of the 34 control mice, said Dr. Prins, professor of urology at the University of Illinois, Chicago.

Almudena Veiga-Lopez, D.V.M., Ph.D., and her associates randomized 12 pregnant sheep to be fed corn oil with or without BPA, and studied their 33 offspring. In each group, they overfed half of the offspring to make them obese. At 15 months of age, fat tissue in the obese sheep had abnormal levels of two markers of inflammation – CD68 and adiponectin – and the CD68 levels also were abnormal in normal-weight female offspring of mother sheep who had been fed BPA, reported Dr. Veiga-Lopez, also of the University of Michigan. Tissue inflammation can be a precursor to metabolic diseases such as obesity, diabetes, or cardiovascular disease, she pointed out.

These are hardly the first studies to trigger alarm about BPA and similar chemicals. Our report from the Endocrine Society’s 2012 meeting highlighted studies showing that children’s weight correlated with their blood levels of another endocrine disruptor, di(2-ethylhexyl)phthalate, and that prenatal exposure to a mixture of endocrine disruptors caused long-term adverse changes in the developing brains of rats.

There’s no easy way to avoid all of these chemicals at the moment, though pregnant women should try, the speakers said. What are really needed are tougher international regulations requiring industry to test new chemicals for safety before introducing them to the market, Dr. Prins said.

All speakers reported having no financial disclosures.

–By Sherry Boschert

[email protected]

On Twitter @sherryboschert