Endocrine Disruptors

What are some examples of endocrine disruptors?

Bisphenol A (BPA)- plastics, Polychlorinated biphenyls (PCB), Phthalate (furniture, clothing, flame retardant), Diethylstilbesterol (DES)- synthetic estrogen, Phytoestrogens (like soy), Pesticides (like DDT)

Where are EDCs found?

water, food, clothing, cosmetics, everywhere…

What is an endocrine disruptor?

a chemical that, when absorbed into they body, either mimics or blocks hormones and disrupts the body’s normal functions

No longer just synthetic, can be natural

How do endocrine disruptors work?

Basic hormone action, normal hormone

Hormone mimic (agonist)

Hormone blocker (antagonist): prevents endogenous hormone action

Why may exposure to EDCs be bad and which specific exposure periods would be more detrimental?

hormones act on behavior

Puberty or pregnancy or in utero

Gene expression and transcription

Accumulation/generational exposure

Feedback systems

Why are EDCs so bad?

endocrine disruptors and target hormone systems

They don’t kill cells or attack DNA

Hormone-disrupting chemicals can cause deficits in individuals without making them sick

These impairments can have serious consequences over a lifetime and for a society

Even small amounts at the right time can have permanent effects

There are more than 85,000 man-made chemicals used for industrial purposes (>350,000 in existence)

Exposure is nearly impossible to avoid: air, food, water, clothing, furniture, etc

Describe the “biggest human experiment ever.”

doctors prescribed DES to almost 5 million pregnant women for decades as a way to decrease miscarriages and produce “bigger and stronger babies”

It was later found to cause reproductive tract deformities, infertility, and uterine and vaginal cancer in female offspring

More recently, reproductive issues have been found in males (e.g. sperm issues)

How have EDCs altered fertility in humans?

volume of ejaculation decreased by 20% in the last 50 years

Decreased sperm counts — from 113 million in 1940 to 66 million in 1990

Decreased sperm motility

Altered sperm morphology

Reduced testicular mass

Correlation with maternal endocrine disruptor stores and testicular cancer

Describe the changes in sex ratio in the Canadian community.

35% boys and 65% girls

Sex ratio was stable and normal until 1993 when it began to drop

Starting in 1999 for 5 years, fewer than 35% of live births were boys compared to the expected of just over 50%

Why did it take so long for the dangers of EDCs to be realized?

EDCs interfere with endocrine action by targeting hormone systems

They don’t kill cells or attack DNA

Hormone-disrupting chemicals can cause deficits in individuals without making them sick

The long latency between exposure and onset of sickness or development of disease makes it difficult to draw associates

Reading Questions

Describe the evidence seen in Herring gulls.

Animals were nesting in female-female pairs

Most birds are biparental but males weren’t helping

Increased rates of pre-hatching deaths

The offspring born to those females demonstrated hermaphroditic characteristics and grotesque deformities

Effects linked to DDT and could be mimicked with treatment with estrogen

Describe the evidence seen in bald eagles.

Dramatic decrease in newly-hatched eaglets

Abnormally thin eggshells

2/3 of the adult birds appeared indifferent to their normal courtship and nesting behaviors

Reproductive failure: 80% of the males were sterile

Birds usually put a lot of effort into mating, eagles stopped

Describe the evidence seen in alligators.

In some lakes in Florida, up to 90% of the eggs laid are hatched

At lake apopka, the hatching barely reached 18%

Half of those born died within 10 days

Of those that made it, males had abnormally small penises and decreased T levels (T and DHT critical for external genetalia)

The effects were linked to increased levels of DDT and dicofol (lake contamination)

Why are PCBs still a problem?

still out there

Chemically stable and resist degradation

Can move easily around the world

Humans are most often exposed via consumption

They’re lipophilic, so they accumulate in the fat of animals and magnify in the food chain

What is at particular risk to PCBs?

Infants who can be exposed to the contaminant both in utero and via lactation during critical periods of development

Communities in western Michigan that rely largely upon Great Lakes whitefish

Individuals exposed occupationally (e.g. firefighters covered in flame retardant)

*What are the effects of PCBs in humans?

thyroid problems (e.g. disrupted metabolism)

Decreased vigor/muscle weakness

Sensory neuropathy (numbness, areflexia)

Delayed cognitive development

ADHD/inability to concentrate

Retarded growth

Reproductive abnormalities—abnormal sexual development, altered fertility

Compromised immune system function

What are some effects of PCBs on animals in the lab?

altered sexual behavior and partner preference

Changes in brain chemistry (DA and 5-HT)

Increased hyperactivity

Altered response to stress

Decreased fertility

What is the traditional experimental paradigm in rodents for EDC exposure?

methods: give through ingestion (mimics human exposure) or injection (control amount)

Offspring exposed in utero, then measure effect

How is a rodent mother’s care altered with gestational PCB treatment?

maternal behavior in rodents is driven by hormones

• progesterone is high throughout pregnancy, then slowly drops near the end when estradiol and prolactin increase sharply

Dams were treated with PCB 77 on gestation days (GD) 6-18

Offspring development and MB were examined

Various measures were altered: pup weight gain, pup survival, time on the nest, pup-directed licking and grooming, high crouch nursing

Why does the traditional experimental paradigm need to be reconsidered?

Virgin females hate offspring

Scientists need to be sure that the effect they’re attributing to the contaminant are due to the contaminant, and not indirect effects on behavior

Changes care based on offspring

What is transgenerational inheritance?

From exposure in one generation: exposure to an ED during pregnancy leads to effects that are transmitted across generations resulting in toxicity that continues (and may be exacerbated) across generations

Disease incidence is compounded over many generations

Are we safe if PCBs have been banned?

in all of the Great Lakes, old contaminants like DDT are declining but are being replaced by new ones, such as flame retardants

How can we defend ourselves?

Action is required on several fronts to minimize exposure to current contaminants and eliminate new sources

• Scientific research, chemical and manufacturing redesign, new government policies, individual efforts

• Know your water

• Choose your food intelligently

  • Avoid animal fat and fatty fish, choose organic produce, avoid microwaving food in plastic or with plastic wrap

What WAS (and no longer is…) being done?

EPA developed an Endocrine Disruptor Screening Program in 1996 to evaluate substance for their potential to affect the endocrine system of humans and wildlife

• developing high through-put methods for evaluating the 87,000 chemicals that are produced today

• 2-tiered screening process

  • Tier 1: identify the chemicals that have the potential to interact with the endocrine system

  • Tier 2: determine the endocrine-related effects caused by each endocrine disruptor