Domestication, Endocrine Disruptors, and Environmental Pollution

Physically Linked Traits and Domestication Syndrome

• Pleiotropic Links: Behavioral genes, specifically those related to reduced stress and domesticability, are pleiotropically linked to physical traits. In domesticated foxes, behavioral changes co-occur with physical changes such as shorter snouts and more forward-facing eyes (sometimes referred to as "dogification").

• Other Covarying Traits: Domesticated mammals often exhibit a suite of traits known as "domestication syndrome," which includes:     - Floppy ears (pinna development).     - Patchy coloration (common in foxes and other domesticated mammals).     - Star-shaped white marks on the head.

• Genetic Networks and Heterochrony:     - In canids, the gene networks controlling the stress response interact with networks impacting facial development.     - Domesticated animal faces often appear more juvenile, a phenomenon known as heterochrony.     - In all placental mammals, stress-related genes appear to interact with gene networks controlling coloration, patterning, and external ear (pinna) development.

Questions & Discussion: Domestication and Stress

• Question: Any questions about domestication and stress?

• Timeline of Domestication (Approximate Years Ago based on Archaeology):     - Dog: $15,000 - 36,000$ years ago in Eurasia.     - Sheep: $11,000$ years ago in the Middle East.     - Goat: $10,500$ years ago in the Middle East.     - Cow: $10,300$ years ago in the Middle East.     - Pig: $10,300$ years ago in the Middle East.     - Cat: $9,500$ years ago in the Middle East.     - Humped Cow: $8,000$ years ago in South Asia.     - Llama: $6,000$ years ago in South America.     - Horse: $5,500$ years ago in Central Asia.     - Alpaca: $5,000$ years ago in South America.     - Camel (Two-humped): $4,500$ years ago in Central Asia.     - Chicken: $4,000$ years ago in East Asia/Middle East.     - Camel (One-humped): $3,000$ years ago in the Middle East.     - Turkey: $2,000$ years ago in North America.     - Duck: $1,000$ years ago in East Asia/Middle East.

Introduction to Endocrine Disruptors

• Modern Threat: Endocrine disruptors are a major contemporary concern regarding pollution.

• Key Resource: Count Down by Shanna H. Swan, PhD (with Stacey Colino), discusses how the modern world threatens sperm counts, alters reproductive development, and imperils human fertility.

• Associated Health Issues: Potential links exist between endocrine disruptors and weight gain, skin problems, sleep disturbances, mood changes, low energy, and difficulty getting pregnant.

• Definition: Endocrine disruptors are chemicals that interfere with endocrine system function by binding to hormone receptors. They can be:     - Estrogenic (mimic estrogen).     - Androgenic (mimic androgens).     - Anti-Estrogenic (block estrogen receptors).     - Anti-Androgenic (block androgen receptors).

• Non-steroid Disruptors: These are less common as environmental pollutants compared to steroid-mimicking compounds.

Characteristics of Steroid Endocrine Disruptors

• Mechanism of Action: Steroids are lipid-soluble, allowing them to easily bind to cytoplasmic receptors and gain access to cell interiors and the nucleus.

• Storage and Persistence: Nonpolar (lipid) compounds are stored in fat cells and do not break down easily.

• Transgenerational Effects: They can sometimes show no obvious effect until the second generation.

• Developmental Disruption: They disrupt normal sexual development, leading to conditions like hermaphroditism, sterility, and abnormal reproductive organs (testes, ovaries).

• Cancer Links: Associated with elevated rates of cancer.

The Dominance of Estrogenic Compounds

• Large Class of Disruptors: Estrogenic compounds represent the largest class of steroid endocrine disruptors.

• Major Categories:     - Dioxins     - Phthalates     - Phytoestrogens (plant products like Genistein, Luteolin, Resveratrol, and Coumestrol)     - Polyaromatic Hydrocarbons     - Pesticides (e.g., DDT, Kepone)     - Polychlorinated Biphenyls (PCB)     - Flame Retardants     - Phenols (e.g., Bisphenol A)

• Why Estrogens are Problematic:     - Nonspecificity: Estrogen receptors (ER) are relatively nonspecific, binding to multiple ligands such as estradiol, estriol, and estrone.     - Evolutionary Age: These are some of the oldest receptors (ancestral receptors tend to be less specific), used in many different endocrine systems.     - Receptor Duplication: Receptors evolved through duplication and modification to receive different ligands.     - Transcription Factors: The hormone-receptor complex acts as a common transcription factor, binding to DNA and regulating gene expression.

Estrogenic Health Impacts

• Cancer Links: Estrogen and ER are implicated in breast ($70\%$ of cases are "ER-positive"), ovarian, colon, prostate, and endometrial cancers.

• Tumorigenesis Mechanisms:     - Estrogen stimulates mammary cell proliferation, increasing cell division and DNA replication, which leads to more mutations.     - Estrogen metabolism produces genotoxic waste.     - Both processes disrupt cell cycles associated with apoptosis and DNA repair.

• Estrogen Dominance Effects: Imbalance caused by high estrogen relative to progesterone can cause:     - Proliferative endometrium and fibrocystic breasts.     - Salt/fluid retention and weight gain.     - Depression, anxiety, and headaches/cyclical migraines.     - Interference with thyroid function and blood sugar control.     - Increased risk of blood clots and gall bladder disease.     - Triggers for autoimmune diseases.

Endocrine Disruptors in the Environment

• Dispersal: These chemicals disperse worldwide via air and ocean currents. They persist in the environment because they are nonpolar.

• Bioaccumulation: Chemicals that are not excreted accumulate in fat cells progressively as animals age. In mammals, they accumulate in milk and high-fat dairy products like butter and cheese.

• Biomagnification: Concentration increases at each higher trophic level of the food chain.     - Example (Lake Ontario):         - Phytoplankton: $0.025\,ppm$         - Zooplankton: $0.123\,ppm$         - Smelt: $1.04\,ppm$         - Lake Trout: $4.83\,ppm$         - Herring Gull Eggs: $124\,ppm$

• Vulnerable Populations:     - Inuit women in northern Quebec, who consume marine mammals, have PCB concentrations in breast milk $2 - 10$ times higher than women in southern Quebec.     - Polar bears in the European Arctic can have concentrations up to $100\,ppm$.

Specific Chemicals and Pesticides

• Main Sources: Pharmaceuticals (e.g., DES), agricultural treatments, golf courses, factories, and plastics.

• Mechanisms of Pesticide Attacks:     - Chlorinated hydrocarbons (DDT, Dioxin): Accumulate in fatty tissue; cause chronic disease.  

•    - Organophosphates (Malathion) and Carbamates: Inhibit acetylcholinesterase.     - Pyrethroids: Neurotoxins.     - Growth regulators (Methoprene): Block juvenile hormone receptors or chitin synthesis.     - Triazines (Atrazine): Inhibit photosynthesis.     - Phenoxy herbicides: Mimic plant hormone auxin.

• Historical Note: In the 1950s, arsenic and copper sulfate were added to Lake Mendota by students to deter algal blooms, often without protection.

• Agent Orange: Used during the Vietnam War ($80$ million liters sprayed); laced with dioxins.

• PCBs (Polychlorinated Biphenyls): $209$ known types; used in electrical transformers and cooling systems; produced in North America from $1929$ to $1977$.

DDT and Case Studies

• DDT (Dichloro-diphenyl-trichloroethane): A synthetic pesticide and estrogen mimic. Banned in Europe/US in $1972$. Still used for malaria control in developing nations.

• DDE: The breakdown product of DDT; acts as an anti-androgen.

• Bald Eagle Case Study: Thinning eggshells caused by DDT nearly led to extinction. After the ban, nesting pairs in the US increased from $791$ in $1974$ to $5,948$ in $1998$.

The Atrazine Controversy

• Usage: The most common herbicide in the U.S.; $84.13\%$ used on corn.

• Concentration Levels:     - Application levels: $2,500,000 - 29,300,000\,ppb$.     - Drinking water limit: $3\,ppb$.     - Effect on Xenopus laevis (frogs): $0.01 - 200\,ppb$.

• Results of Exposure: Atrazine (> 0.1\,ppb) induces hermaphroditism and demasculinizes frog larynges. Exposure to $25\,ppb$ causes a $10$-fold decrease in testosterone.

• Mechanism: Induces aromatase, which converts testosterone into estrogen.

• Scientific Significance: Dr. Stanley Dodson called the Hayes et al. paper "the most important paper in environmental toxicology in decades."

Historical Context of Pollution and Regulation

• 1800s - 1950s: Industrial Revolution and the "Age of Optimism," fostering a belief that technology could solve all problems and achieve the "Conquest of Nature."

• 1960s - 1970s: Environmental disasters (Cuyahoga River fire, LA Smog) sparked the environmental movement.

• Rachel Carson: Published Silent Spring (1962), predicting a loss of birds due to pesticides.

• Regulatory Acts:     - EPA created in $1970$ (William D. Ruckelshaus was the first administrator).     - Clean Air Act ($1970$).     - Safe Drinking Water Act ($1974$).     - Clean Water Act ($1977$).

• Current Status: Environmental laws are often targeted for weakening via omnibus bills or "new guidance" from partisan appointees. This is described as a "death by a thousand cuts" approach.

Lead Pollution and the Lead-Crime Hypothesis

• Health Risks: No safe level of lead exposure for children. It causes irreversible neurological damage, especially in children under $10$. It interferes with neural connections before neural pruning occurs.

• Behavioral Impact: Youth exposure is linked to poor impulse control and violence.

• Lead in Gasoline: Added in the $1920s$ to reduce "engine knock" and boost octane. Chemists warned of risks in the $1940s$, but warnings were buried by the auto industry.

• Banning Lead: Lead ruined catalytic converters mandated by the EPA in the $1970s$, forcing a phase-out.

• The Lead-Crime Link: Environmental lead levels track perfectly with violent crime rates with a $23$-year lag.

• Societal Impact: "Lucifer Curves" (by Rick Nevin) show this trend in New Zealand, Australia, Britain, and Canada. Much of the high crime in US cities from the $1960s - 1980s$ was likely due to lead poisoning rather than inherent traits of those locations. Lead remains in soil in poorer urban areas today.

• Research Status: The "lead-crime hypothesis" is widely accepted, though some debate remains on the exact percentage of crime it accounts for (e.g., one paper claims lead is responsible only for $1/3$ of the falling murder rate in the $1990s$).