Where is Captain Planet when you need him?

I briefly provided some background on this weeks topic in a previous blog (“Surrounded by poisons; understanding the world fish face in today’s aquatic environment”). Here I expand on that subject.  

Clutching the bottle of water I had just collected from the Pee Dee River, I climbed the steep embankment back to our truck wondering how much estrogen we would find in our sample. We spent the better part of a month driving across North Carolina to examine a suite of chemicals called endocrine disruptors in surface waters. These chemicals have been associated with harmful effects in aquatic animals and people across the globe.


Other than the nervous system, the endocrine system is the primary means for the body to conduct internal communication. This system includes glands that release chemicals (hormones) into the blood to relay messages to other parts of the body. These messages are delivered when that chemical binds to a specific receptor at a target location and causes some physiological response. For example, in fish, estrogen is released from the female gonad, travels through the blood to the liver where it binds to a receptor and causes the liver to make a yolk protein called vitellogenin.   

A schematic of the endocrine system (source unknown). The red triangles represent a hormone.

Endocrine disruption is, therefore, when a chemical from outside the body interferes with any part of the endocrine system (e.g. hormone production, release, transport through the blood, binding to a receptor, etc.). While there are numerous endocrine disruptors in the environment, one of the most common types of disruption currently studied in aquatic systems is estrogen mimics. This is a big problem for male fish because even they have estrogen receptors and environmentally relevant concentrations of these chemicals can cause a number of adverse effects.

An example of endocrine disruption (source: http://www.niehs.nih.gov/news/newsletter/2009/july/extramural-update.cfm)

One of these is the production of vitellogenin (the female yolk protein mentioned above). In fact, the presence of vitellogenin in males is often used as an indicator of estrogenic chemical exposure. Other adverse effects include reduced sperm motility, and eggs developing in the testes of male fish (intersex or feminized males). As I mentioned in a previous blog article, these effects have been linked with fish population declines. Also worrisome, Hinck et al. (2009) recently reported widespread intersex in the United States with the highest concentrations of feminized males (67-91% of all male fish collected) in the Pee Dee River in North and South Carolina (one of the reasons we were sampling that system).

The effect of several estrogenic compounds, including a mixture of all five, on vitellogenin production in male rainbow trout (source: Sumpter and Jobling 1995).

Even more problematic, endocrine disruptors do not seem to have a typical dose-response curve. A typical dose-response curve is generated during standard testing of a chemical and shows an increase in an effect (e.g. mortality) with an increase in that chemical. These curves are used to determine “safe” concentrations of that chemical (the highest concentration at which no response is seen) and the “safe” concentrations are then used to determine safety regulations.

A typical dose response curve used in standard chemical testing protocol (source: Introducing dose-response curves, http://graphpad.com/curvefit/introduction89.htm)

A recent review by Vandenberg et al. (2012) shows endocrine disruptors seem to have a “U” shaped dose-response curve, where the effects seen at extreme low doses (below those tested in standard testing protocols) cannot be predicted by effects seen at high doses. These results address one of the biggest controversies over endocrine disruptors, whether the tiny doses that most animals and people are exposed to are harmful; the accumulated evidence suggests that it is. Consequently, many scientists are now pushing for fundamental changes in chemical testing for endocrine disruptors and suggesting we re-test a number of chemicals currently on the market to protect the health of our ecosystems.

 

From Vandenberg et al. 2012: No observable adverse effect level (NOAEL), the lowest observable effect level (LOAEL), and calculation of a safe reference dose in traditional toxicology testing are indicated (several safety factors are applied to the safe dose to derive the reference dose, i.e. the dose at which exposures are presumed safe.) This reference dose is rarely tested directly. Here, the doses that would be tested are shown by a dotted line, and the calculated safe dose is indicated by a solid line. The actual response, an inverted U-shaped nonmonotonic dose-response curve is also shown.

Fish are not the only ones influenced by endocrine disruptors, humans have been battling the consequences of estrogens and estrogen mimics as well. The title of this Newsweek article from March 1994 says it all, “The Estrogen Complex: Sperm counts down: Penises shriveled? Hey Rush, don’t blame it on feminists. It may be from chemical pollutants in water and food.” Since this article was published, female and male related cancers and other disorders have also been linked to these chemicals.

From Hinck et al. 2009: Histological observations of intersex in fish. (A) Testicular oocytes (arrows) observed within testes of a largemouth bass from the Pee Dee River. Note mature sperm (circle) within the tubules. (B) Oocytes (arrows) within testes of a smallmouth bass from the Colorado River. (C) Oocyte (arrow) within an immature testes of a channel catfish from the Colorado River. (D) Foci of sperm (arrows) within the ovary of a common carp from the Colorado River. Scale bar = 100_m. H&E stain.

Some steps have been made to prevent exposure to people; for example next time you find yourself in a store, peruse the baby isle and notice how many items now say BPA free. BPA stands for bisphenol A, an estrogen mimic commonly found in plastics and cans that is infamous for fooling estrogen receptors everywhere. However, there are still numerous endocrine disruptors out there wreaking havoc on the aquatic environment and our own endocrine systems. Indeed, aquatic species may be sentinels of the growing endocrine disruption problem at our doorstep.

An example of BPA-free baby bottles. This image was associated with an article on CA state legislature, named the Toxin-Free Toddlers and Babies Act. Source: http://sundial.csun.edu/2010/08/bpa-free-baby-bottles/

As you may have seen from Patrick Cooney’s blog last week, North Carolina’s legislator recently approved the practice of fracking. In addition to releasing carcinogens and methane into the environment, fracking also introduces many endocrine disruptors. I can only hope that my childhood hero, Captain Planet, can fly in with his flowing green mullet to buy back that vote from Captain America.

Source: http://www.zakiscorner.com/2012/03/nostalgia-theater-captain-planet-ted.html

References and Resources:


http://www.democracynow.org/2010/4/14/world_renowned_scientist_dr_theo_colborn

Cone M. 2012. Low doses, big effects: Scientists seek 'fundamental changes' in testing, regulation of hormone-like chemicals. http://www.environmentalhealthnews.org/ehs/news/2012/low-doses-big-effects

Heindel J. 2009. Endocrine Disruptor Research: It’s not just toxicology. http://www.niehs.nih.gov/news/newsletter/2009/july/extramural-update.cfm

Hinck JE, VS Blazer, CJ Schmitt, DM Papoulias, and DE Tillitt. 2009. Widespread occurrence of intersex in black basses (Micropterus spp.) from U.S. rivers, 1995–2004. Aquatic Toxicology 95: 60-70.

Sumpter, J.P., S. Jobling. 1995. Vitellogenesis as a biomarker for estrogenic contamination of the aquatic environment. Environ. Health Perspect. 103(Suppl 7):173-178.

Vandenberg LN, Colborn T, Hayes TB, Heindel JJ, Jacobs, Jr. DR, Lee D-H, Shioda T, Soto AM, von Saal FS,Welshons WV, Zoeller RT, Myers JP. 2012. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocrine Reviews doi:10.1210/er.2011-1050