Another very interesting and frightening article on the effects of exogenous estrogen on the human reproduction system and its possible connection with the western obesity epidemic. Our plastic dreams are certainly turning into nightmares. The whole article can be found here.

The Toxic Origins of Disease
Liza Gross, June 26, 2007

Researchers say endocrine-disrupting chemicals can permanently harm the developing organism and may even promote obesity. But the chemical industry doesn’t want you to believe them.

Never in his wildest dreams had Fred vom Saal pictured himself studying urethral outlet obstruction. Nor, for that matter, had he ever thought much about the causes of obesity. For most of his 30-year career, vom Saal, a developmental biologist at the University of Missouri, studied the harmful consequences of tiny changes in natural hormone levels at critical periods during the development of the brain and reproductive tract. But he began to include synthetic chemicals in his investigations when he learned that pesticides and other environmental contaminants caused reproductive defects in wildlife much like those seen in lab animals exposed to abnormal estrogen levels.

During embryonic development, steroid hormones like estrogen control gene-expression programs to coordinate cell differentiation, growth, organogenesis, and metabolism. Adding extra estrogen—whether foreign (exogenous) or natural (endogenous)—can irreversibly alter these developmental processes by mimicking, blocking, or otherwise disrupting pathways that have been fine-tuned over millions of years to respond to minuscule changes in hormone levels. Diethylstilbestrol (DES) offered a tragic illustration of the risks of exposing a fetus to synthetic compounds that mimic the behavior of endogenous estrogen: the drug was prescribed to millions of pregnant women before doctors realized it was causing rare cancers in their daughters.

To understand how exogenous estrogens interfere with developmental pathways, vom Saal started by feeding pregnant mice minute doses of DES, along with the endogenous estrogen estradiol, which he had long studied. In both cases, giving the mother these estrogens when prostate development is occurring raised fetal estrogen levels ever so slightly, with profound consequences: male offspring experienced accelerated prostatic gland growth and showed permanent increases in both the number of androgen receptors (androgen mediates prostate differentiation) and the size of the prostate.

But it wasn’t until vom Saal reported similar effects from a synthetic chemical still in mass production that his research focus, and his life, would take an unexpected turn. In 1997, vom Saal’s group reported that feeding pregnant mice trace amounts of bisphenol A—the building block of polycarbonate plastics—caused enlarged prostates in male offspring, just as estradiol and DES had. “Our findings,” the researchers wrote, “show for the first time that fetal exposure to environmentally relevant parts-per-billion (ppb) doses of bisphenol A, in the range currently being consumed by people, can alter the adult reproductive system in mice”.

The next year, vom Saal’s group showed that a similar treatment with bisphenol A also shrinks seminal vesicles, enlarges preputial glands (which produce sex pheromones), and reduces sperm efficiency [3]. The 1998 study, which observed these effects at a dose six times lower than a patient might swallow during application of a plastic dental sealant, immediately caught the attention of the chemical industry—and transformed Fred vom Saal into a tireless crusader against bisphenol A.

An Obscure Chemical Enters the Limelight
For over 40 years, bisphenol A labored in relative obscurity as the feedstock for a wide range of commercial plastics and synthetic resins. Growing demand for polycarbonates—for products ranging from baby bottles to compact discs—drives the rapidly expanding multibillion-dollar market for bisphenol A, one of the highest-volume chemicals in commercial production [see related essay (published online 17 July 2007); doi:10.1371/journal.pbio.0050200]. Bisphenol A molecules, which are joined by unstable bonds to form polycarbonates and resins, leach from containers exposed to heat or highly acidic or basic compounds. Although bisphenol A’s estrogenic activity was first reported in 1936, scientific interest in the chemical has recently increased along with evidence of its effects. And as the media increasingly cover these findings, the chemical industry has stepped up its attacks on those studying endocrine disruption.

“The moment we published something on bisphenol A, the chemical industry went out and hired a number of corporate laboratories to replicate our research. What was stunning about what they did,” vom Saal says with a mix of outrage and bemused disbelief, “was they hired people who had no idea how to do the work. Each of the members of these groups came to me and said, ‘We don’t know how to do this, will you teach us?’”

Vom Saal videotaped his protocols for a group hired by Dow Chemical, and sent one of his students to England to teach AstraZeneca scientists the system. By 1999, a flurry of studies appeared from AstraZeneca [4–8], along with a collaborative effort sponsored by the Society of the Plastics Industry (SPI) from the labs of Dow, Shell, General Electric, and Bayer, the major bisphenol A producers [9]. (AstraZeneca does not make bisphenol A, but it produces a number of pest-control products that could face similar scrutiny.) None of the studies found that low doses of bisphenol A harm the developing prostate.

The next year, however, a study came out that supported vom Saal’s findings [10]. Channda Gupta, then a professor of pharmacology at the University of Pittsburgh School of Medicine, fed pregnant mice low doses of bisphenol A, aroclor (an estrogenic pesticide), and DES, which she used as a positive control, as vom Saal had. (If animals fail to respond to DES, whose effects are well understood, it’s a sign that the setup is flawed.) Gupta also observed increased prostate size and gland number in male offspring. When she placed the developing prostate in culture and treated it with the chemicals, she saw the same abnormal prostatic growth—indicating that the chemicals targeted the prostate directly.

Now vom Saal has gone even further with his rodent studies to show that bisphenol A activates androgen and estrogen receptor genes in the embryonic cells that give rise to prostate tissue [11]. This gene activity accelerates the proliferation of epithelial cells in prostate ducts, inducing prostate growth, and permanently increases the number of androgen receptors. “One of the consequences of that is that cells become hyper-responsive to hormones for the rest of the life of the individual,” he explains, “and that’s a risk factor for humans for prostate cancer.” The overgrown prostate ducts also squeeze the urethra, constricting its passage out of the bladder—a condition similar to bladder outlet obstruction disease.

The year after Gupta’s study appeared in Experimental Biology and Medicine, the journal ran a commentary, written by Barbara Elswick, Frederick Miller, and Frank Welsch of the Chemical Industry Institute of Toxicology (CIIT), faulting her analytical methods and conclusions [12]. The CIIT was “created by farsighted chemical industry leaders,” according to its Web site, and is funded by the American Chemistry Council (ACC). The CIIT scientists, who no longer work at the institute, could not be reached for comment.

Gupta’s response defended her original conclusions and pointed out: “It is interesting to note that the studies that failed to find an effect of this chemical are funded by the chemical industries, whereas positive findings are reported by independent academic laboratories. What is also clear is that scientists who choose to study a chemical of commercial importance are subjected to intense scrutiny by the chemical industry and by the scientists funded by these industries”

Read the rest of the shocking story here.

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