Sex genes of fish disrupted by common household products

July 29, 2002

BALTIMORE, Md.--Traces of ordinary products, flushed and tossed away from millions of homes, gardens and garages, are likely more harmful to the sexual development and reproduction of fish in the Chesapeake Bay than scientists previously thought. The large, shallow Bay-average depth of less than 30 feet-with hundreds of tributaries, has long been considered by ecologists as a very favorable habitat for fish spawning, hatching and nurseries.

However, today, at the annual meeting of the Society for the Study of Reproduction, at the Baltimore Marriott Waterfront Hotel, scientists of the University of Maryland Biotechnology Institute (UMBI) reported that the list of compounds in human pollution that can disrupt fish sexual hormones-a concern of scientists for the past 20 years-has widened considerably.

Compounds in many detergents, plastics, pesticides, some medicines, and even thalates ("new car smell") disrupted the sexual development of juvenile zebra fish in experiments at UMBI's Center of Marine Biotechnology (COMB) in Baltimore.

"I would not say that it is severe enough that any population is becoming completely monosexed. However, because the Bay is so important as a nursery, chemical-induced perturbations of the reproductive and developmental processes could lead to severe consequences," said John Trant, COMB associate professor. All of the environmental pollutants were tested at concentrations that can be found in the Chesapeake Bay system.

It has been known for a long time that some environmental chemicals (endocrine disrupting chemicals; EDCs) disrupt reproduction by mimicking natural estrogens.

Trant reported that the most worrisome finding from a two-and-a-half year COMB study was that there are many additional classes of environmental chemicals that are functioning as EDCs and that these chemical are interacting directly with genes that are critical for reproductive success.

He said, unlike most animals, many fish produce two forms of a gene responsible for the enzyme aromatase that, in turn, makes estrogen. One form is in the ovaries and the other is in the brain. It appears that the direct chemical disruption of the brain aromatase gene, which directly affects brain estrogen production, may be a key mechanism for the EDC-induced disruption of the developmental and reproductive capacity of fish.

The researchers first found that the differential expression of the brain aromatase gene was associated with sex differentiation. "It became clear that compounds that affect this gene will thereby affect sex and sexual behavior in fish," concluded Trant. In other words, COMB researchers found that the EDCs can regulate the aromatase gene in the brain, affecting more than if a fish turns out to be male or female.

"What is dangerous is that in-between stuff," offered Trant. "You might get males who do not display the correct behavior. In order to mate with a female, he may have to court her, build a nest, chase, or show some dominance. So, even if the concentration of these disrupting compounds in the water are not sufficient to completely reverse their sexual physiology, small adjustments in their behaviors would be equally fruitless."

A growing number of scientists theorize that endocrine disrupting compounds in the water behaves chemically like hormones in fish tissues and cells. When compounds such as polychlorinated biphenyls, dioxins, certain plasticizers, and some detergent additives are in streams or rivers, groups of fish, birds, frogs and other animals are sometimes found to be all male, or all female, or are partially both sexes in their genitalia.

Historically scientists have suspected actual estrogens or chemicals that mimic estrogens in pollution as the causes of the gender bending effects on fish. Estrogen (or estrogen-like) molecules dock onto a structure called an estrogen receptor in the cells of the

liver, ovaries, fat, breast, brain, bone and many other target tissues in man. The activated receptor initiates a series of changes into action related to sexual physiology. Many of the pollutants, such as PCB's, some pesticides and petroleum products in the Chesapeake waters are recognized as estrogen molecules by fish and human cells.

"That's why scientists have focused there," said Trant. "But, this is worse than we thought before. This is not simply toxicology. It is interfering with the reproduction of the adults, and potentially skewing sex ratios of the populations."

The COMB team of Yakinori Kazeto, Allen Place and Trant reported that the aromatase gene expression in zebrafish was changed by multiple classes of pollutants such as estrogen mimics (or xenoestrogens, such as surfactants in detergents and pharmaceuticals), arylhydrocarbons (PAH's and benzo(a)pyrine), peroxisome proliferators (i.e. pharmaceuticals and plasticizers), and herbicides (atrazine).

"For people looking for a magic bullet of why productivity of the Chesapeake Bay is down, this is not it. There are probably many causes," commented Trant. "But this is certainly affecting the reproductive health of animals that spawn here and the developmental health of animals that are raised in the Chesapeake Bay."

Scientists have just been looking "too narrowly at estrogen mimics," said the researchers. They added that it's almost certain that the multiple compounds are affecting all the fish in the Bay and beyond, not just zebrafish in the laboratory. (The small zebrafish is widely accepted as an excellent model for fish studies.)
The University of Maryland Biotechnology Institute was mandated by the state of Maryland legislature in 1985 as "a new paradigm of state economic development in biotech-related sciences." With five major research and education centers across Maryland, UMBI is dedicated to advancing the frontiers of biotechnology. The centers are the Center for Advanced Research in Biotechnology in Rockville; Center for Agricultural Research in College Park; and Center of Marine Biotechnology, Medical Biotechnology Center, and the Institute of Human Virology, all in Baltimore.

University of Maryland Biotechnology Institute

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