Reproductive Toxicology
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Reproductive Toxicology

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A brief overview of my field, Reproductive Toxicology.

A brief overview of my field, Reproductive Toxicology.

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Reproductive Toxicology Reproductive Toxicology Presentation Transcript

  • Reproductive Toxicology
    Erin Legacki
    December 6, 2009
    Animal Biology 290
  • What is Reproductive Toxicology?
    Effects of chemicals on the reproductive and neuroendocrine systems
    the embryo, fetus, neonate and prepubertal mammal.
  • Modes of Disruption
    Morphology Disruption
    Reproductive tract malformation
    Hermaphrodite
    Endocrine Disruption
    Feminization
    Altered circulating hormones
  • Usual Suspects
    Dichlorodiphenyltrichloroethane
    DDT
    Pesticide
    BisphenolA
    BPA
    Plastics
    Found in polycarbonate
  • Silent Spring: Classic Examples
    Rachel Carson – 1962
    Chronicled DDT effects on wildlife
    Bird Focus
    Bald Eagle
    California Condor
    Thinning of egg shells
  • Morphology Disruption
    Alterations to the reproductive tract
    In utero
    Hormone sensitive tissue
    Hermaphroditic
  • Diethylstilbestrol - DES
    Synthetic estroegn
    Developed in 1938
    Prescribed to prevent miscarriages/premature births (1938-1971)
    5-10 million exposed
    DES Daughters
    Reproductive tract malformation
    Cancer ( breast and cervical)
  • Arctic Problem
    1 in 50 female Polar Bears are hermaphrodites
    High levels of polybrominateddiphenyls
    Little more then 50% have cubs
    Of 45 Beluga whales 41% had breast tumors
    Compromised milk production
    1 was hermaphroditic
    High levels of organochlorinated compounds
  • Amphibians
    Frogs
    Atrazine causes hermaphroditic reproductive tracts
    Feminization
    Salamanders
    Endosulfan disrupts pheremones
    Alters developing glands
    Global amphibian decline
  • Testicular Dysgensis Syndrome
    Cryptorchidism
    Hypospadia
    Low Sperm Count
    Testicular germ cell death
    Cancer
    15% of all couples are infertile
    20% is male infertility
  • Endocrine Disruption
    Several modes of disruption
    Mimic
    Bisphenol A
    Block
    Flutamide
    Metabolize
    Dexamethasone
  • Hormone Mimics
    Similar affinity
    Activate pathway
    No regulation
    Changes in hormone levels
  • Receptor Blockers
    Bind to receptor
    Compete with hormone
    Block feedback
    Changes in hormone level
  • Hormone metabolism
    Up-regulation of hepatic and renal clearance
    Dexamethasone
    Up-regulates CYP 3A
    Testosterone to 6β- hydroxytesterone
    Polybrominateddiphenyl ether (PBDE)
    Increased hepatic enzyme activity
  • Lake Apopka Alligators
    Tower Chemical Company Spill – 1980
    Mass die off of alligators
    Decrease in clutch viability
    Juvenile mortality
    20 years later
    Decrease in testosterone
    Small phallus size
    Altered reproductive tract
  • Back to male infertility
    Decline in male fertility (101 studies in 28 countries)
    113 million sperm/ml in 1938
    66 million sperm/ml in 1991
    1.5% / year decline in the US
    No clear reason why???
  • Phthalate Esters
    Anti-androgen compounds
    Make plastics flexible
    Children’s toys
    Medical equipment
    Enteric coating of pharmaceuticals
    Malformation of reproductive tissue
    Multinucleated germ cells
    Decreased Sperm Count
  • Sertoli Cell
    Primary support for germ cells
    Paracrine
    Anti-Mullerican Hormone
    Follicle Stimulating Hormone
    Structural
    Tight Junctions
    Immune protection
  • Sertoli Cell + Phthalates
    In Utero
    Decreased Anti-Mullerian Hormone
    Germ cell death
    Retracted cytoplasic processes
    Pre-Pubertal
    Disruption of tight junction proteins
    Vimentin
    Connexin 43
  • Mode of action?
    Suggested anti-androgen
    Testosterone changes in rats
    Not Mice
    Disruption of androgen dependent tissue
    Flutamide
    Know androgen receptor block
    Compare to phthalate disruption
  • Questions??