Teratogens

1. Biology of Toxins Final Presentation Spring ‘08 Teratogens - substances that may cause structural and/or functional fetal abnormalities (dose dependent)

2. Biology of Toxins Final Presentation Spring ‘08 Teratogens Introduction Social and Behavioral Teratogens Alvena Largo Psychoactive Drugs and Diseases Candice Lovato Environmental Toxins and Fetal Development Jennifer Rice Teratogens: Medications Katie Weeks

3. Introduction • Critical periods during Fetal Development www.cerebralpalsychildren.com/CP1.jpg

4. Introduction • Teratogens vary from recreational and medicinal drugs to behavior and environmental factors. The devastating effects of many teratogens depends on gestational timing and duration of exposure. • The following presentation reveals some of the most common and hazardous teratogens.

5. Social and Behavioral Teratogens • Alvena Largo news.bbc.co.uk

6. Social and Behavioral Teratogens • Stress • Diet • Caffeine news.bbc.co.uk

7. wpclipart.com Stress • Leads to many problems for mother and fetus. • Pre-term births and low birth rate are some dangers for the fetus (March of Dimes).

8. posetech.com/training/images/treadmillrunning.jpg Reducing Stress • Follow good healthy habits such as a good diet and getting plenty of rest (Organization of Teratology). • Excess of stress can also lead to bed rest as well as taking other medications. • Exercise is a Taboo when pregnant, however it can increase blood flow to the baby which is good. • Do not proceed with exercise if pain occurs and sustain from exercising baby area.

9. Foods to stay away from!!! Its important to watch what you eat when pregnant because some food may contain Listeria Bacteria • Seafood- Source of Omega 3fatty acids, but contains Mercury and other bacteria • Deli Meats- may cause food-borne illnesses • Dairy Products- potentially causes illness if not using pasteurized products (Harms, Roger W. M.D., et al) fishfloridakeys.com/stonecrab.htm

10. Other things to prevent sickness while pregnant: • Wash hands, clothes as necessary • Cook all food well!! • Avoid ALL raw foods!! www.nbutexas.com/Images/washing_machine.png

11. Caffeine • Caffeine is a stimulant found in many foods, beverages and plants (naturally). • Increases alertness within 1 hour and lasts up to 6 hours. • Although increased consumption doesn’t cause birth defects, its important to remember that caffeine will cross the placenta and can affect the fetus (Cnattingius S, et al) • Some studies have shown than in combination with alcohol or smoking may cause miscarriages. • Women should also be aware that caffeine can also be passed through breast milk (Organization of Teratology).

12. Psychoactive Drugs • Candice Lovato www.azag.gov

13. Psychoactive Drugs • Among women of reproductive age (15-44) • 90% have used alcohol • 44% have used marijuana • 14% have used cocaine (Rayburn, 2007)

14. Psychoactive Drugs Most women abstain or decrease substance use once their pregnancy is medically diagnosed. However, diagnosis may take as long as one to several months post conception. The first three months of pregnancy are crucial for fetal development. Therefore, substance use during this time may be detrimental to the fetus. www.fshtest.com/fhc-114.jpg

15. Psychoactive Drugs • Alcohol is one of the most common causes of birth defects in the U.S. and therefore one of the most researched.(Gundogan et al., 2007) www.cap.org.uk/.../0/bottles2_300_afoncn.jpg

16. Psychoactive Drugs • Some of the clinical features of Fetal Alcohol Syndrome are: • Growth deficiency (pre and postnatal) • Abnormal facial features (small eyes, sunken nasal bridge, smooth skin surface between nose and upper lip, etc) • Central Nervous System dysfunction (Fryer et al., 2007) • Defects in brain morphology (attributed to abnormal cell growth, differentiation and migration) (Cuzon et al., 2008)

17. Psychoactive Drugs files.turbosquid.com Fetal nicotine exposure increased risk for : spontaneous abortion, limb malformation, defects in lung and urinary tract development. (Berger, 2006) Fetal marijuana exposure increased risk for: defects in Central Nervous System, delayed fetal growth. (Berger, 2006) byrumjason.files.wordpress.com

18. Psychoactive Drugs • Fetal cocaine exposure increased risk for: premature labor, delayed fetal growth, fetal death, symmetric growth restrictions and childhood learning disabilities. www.brake.org.uk/resources/images/Cocaine.jpg

19. Diseases • Candice Lovato www.lurican-pictures.co.uk/.../rubella.PNG

20. Diseases • If a woman has certain diseases while pregnant, it may harm the fetus during the gestational period or during delivery. • It is therefore very important to maintain good health during pregnancy as well as attend regular medical appointments.

21. Diseases • Rubella: An acute, contagious viral infection. In the three trimesters of pregnancy, the embryo is more vulnerable to the virus. It may cause blindness and deafness. It may also cause brain damage. (Berger, 2006 and http://www.healthscout.com)

22. Diseases • Toxoplasmosis: An infection caused by a parasite, remains in the host for life. If a pregnant women is infected, her baby will be born with the disease. It may cause blindness, deafness, cerebral palsy, brain damage and mental retardation. (Berger, 2006 and http://www.medicinenet.com)

23. Diseases • Syphilis: a sexually transmitted bacterial infection. A child may contract the infection during birth or during pregnancy. May cause damage to the brain, bone and may even lead to death. (Berger, 2006 and http://www.pregnancy-info.net)

24. Diseases • Infections of the gums, teeth and urinary tract: non-specific infection Minor infections may lead to premature birth, which may have several adverse effects on the child. (Berger, 2006)

25. Links to Information on Fetal Development • http://channel.nationalgeographic.com/episode/in-the-womb-2228/#tab-Videos/01586_05 • http://health.discovery.com/centers/pregnancy/americanbaby/fetaldevelopment.html • www.babycenter.com

26. Work Cited • CuzonV., Yeh,P. Yanagawa,Y., Obata,K., and Yeh,H. 2008. Ethanol consumption during Early Pregnancy Alters the Disposition of Tangentially Migrating GABAergic Interneurons in the Fetal Cortex. Journal of Neuroscience 28: 1854-1864. • Fryer,S., McGee,C., Matt,G., Riley,E. and N,S. 2007. Evaluation of Psychopathological Conditions in Children With Heavy Prenatal Alcohol Exposure. Pediatrics 119: 733-741. • Gundogan,F., Elwood,G., Longato,L., Tong,M., Feijoo,A., Carlson,R., Wands,J. and de la Monte,S. 2007. Impaired Placentation in Fetal Alcohol Syndrome. Plancenta 29: 148-157. • Rayburn,W. 2007. Maternal and Fetal Effects from Substance Use. Clinics in Perinatology 34: 559-571. • Berger,K.S. 2006. The Developing Person. NY: Worth Publishers • http://www.medicinenet.com

27. Work Cited • http://www.healthscout.com

28. Environmental Toxins and Fetal Development Jennifer Rice

29. Environmental Toxins • Environmental toxins can enter the body of a pregnant woman in several ways: • Drinking Water • Contamination from Food Packaging • Air Pollutants www.allposters.com

30. Methods of Investigation • We have increasing knowledge about the effects of environmental toxins, from research using: • Animal Models • Human longitudinal and epidemiological studies

31. Toxins in our water: TCE & TCA • TCE is an industrial chemical • In its manufacture, use, and disposal, groundwater can become contaminated • TCA is a TCE metabolite • Water treatment with chlorine produces TCA

32. Toxins in our water: TCE & TCA • Gestational exposure to TCE and TCA has been linked with increased risk of congenial heart defects in humans • The EPA recommended safe limit for human exposure is 5ppb (parts per billion) pubs.rsc.org

33. Toxins in our water: TCE & TCA • Chicken embryos • Chicken embryos were given TCE and TCA levels near the EPA limit for humans • Exposure during late cardiac development lead to heart malformation and dysfunction

34. Toxins in our Food • Bisphenol A is an estrogenic compound used as monomer to manufacture: • Polycarbonate plastic • The resin used to line most food and drink cans

35. Polycarbonate and Bisphenol A • Ester bonds in polycarbonate are easily hydrolyzed by high temperatures or high/low pH • Human fetuses, at birth, have 2-3 ng/ml biologically active bisphenol A in their bodies www.dwell.com www.backcountrygear.com

36. Polycarbonate and Bisphenol A • Mice • Exposed during pregnancy to levels of bisphenol A lower than average human levels • Male offspring have malformation and enlargement of prostate • In humans a similar effect is likely to increase rates of prostate cancer later in life

37. Toxins in our Air • There is a wide variety of air pollutants distributed throughout the world • Sources of toxins: • Vehicles burning diesel and gasoline • Power plants burning coal • Burning of wood for heat and cooking • Industrial incineration of waste www.abc.net.au

38. Toxins in our Air • Some of the most dangerous air pollutants are Polycyclic Aromatic Hydrocarbons (PAH) • They are known carcinogens and mutagens in humans • TCDD (Dioxin) is one of the most harmful www.spitzer.caltech.edu

39. Toxins in our Air • In Great Brittan • Children born near “hot spots” of toxin emissions showed at much higher risk of childhood cancers • Most of the 22,458 cases of childhood cancer and leukemia studied could be traced back to atmospheric contaminants.

40. Polycyclic Aromatic Hydrocarbons • In Krakow, Poland and New York City • Increased exposure to PAH, even at low levels, leads to reduction in birth weight • Low birth weight and early delivery have been associated with developmental and health problems as the child grows. www.uwm.edu

41. Focus on a dangerous toxin: TCDD • 2,3,7,8-tetrachlorodibenzo-p-dioxin • Known as Dioxin, or TCDD • Persists in the environment a long time, and has a long half-life in humans www.chm.bris.ac.uk

42. TCDD in human tissues • Most people have ~2-5 ppt (parts per trillion) in their bodies, even without an obvious exposure source • Dioxin compounds tend to accumulate in adipose tissue • Women have more adipose tissue, so higher concentrations of TCDD than men

43. Fetal exposure to TCDD • Toxins that are lipid-soluble tend to cross through the placenta by simple diffusion • Dioxin is also transferred through breast milk, which can carry lipid-soluble compounds • These lead to higher concentrations of TCDD in the fetus and newborn than in the mother www.dgfett.de

44. TCDD and Thyroid Function • TCDD has a similar structure to thyroid hormones • TCDD competes with normal thyroid hormones, leading to symptoms of hypo-thyroidism • Exposure from placental transfer and breast milk may lead to thyroid dysfunction in infants www.answers.com Dioxin www.ktf-split.hr Thyroid Hormones

45. TCDD and Immune Function • Fetal exposure to TCDD has been linked to impaired function in: • Cytotoxic T-cell response • Delayed-type hypersensitivity • Graft vs. host response • Thymus and bone-marrow function • Resistance to bacteria and bacterial toxins www.karlloren.com

46. TCDD and Immune Function • Mice were exposed to prenatal doses of TCDD similar to normal human exposure • Adult offspring were exposed to Influenza A • Immune impairment was dose- and sex-dependent • Higher exposure lead to greater immune system impairment • In male offspring, only the innate response was impaired, while in females, both innate and adaptive responses were affected www.molvray.com

47. TCDD Mechanism of Action • The Aryl hydrocarbon Receptor (AhR) is a ligand-activated transcription factor • TCDD acts as a ligand for AhR in the cytosol • When it binds AhR, an inhibitor protein leaves • AhR moves to the nucleus and binds Dioxin-response elements (DREs) in 5’ region of target genes

48. TCDD Mechanism of Action • Exposure to TCDD leads to upregulation of • CYP1A1 and CYP1B1 • Other drug-metabolizing enzymes • Genes that regulate the cell cycle • Inflammatory mediators www.cbp.pitt.edu

49. Environmental Toxins • We have looked at the effects of: • TCE and TCA in drinking water  congenital heart defects • Bisphenol A  prostate malformation and enlargement • Air pollutants  childhood cancers and leukemia • PAH  low birth weight and early delivery www.thetripflare.org

50. Environmental Toxins • TCDD/Dioxin • concentration in fetus through placenta and breast milk • thyroid dysfunction • Impaired immune response • Disruption of gene expression www.measurement.gov.au