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

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