Environmental Disruption of Animal Development PDF

ENVIRONMENTAL DISRUPTION OF ANIMAL DEVELOPMENT Teratology is the study of birth defects of a structural nature that arise during embryonic development. The agents responsible for these disruptions are called teratogens. Teratogens work during certain critical periods of developm...

ENVIRONMENTAL DISRUPTION OF ANIMAL DEVELOPMENT Teratology is the study of birth defects of a structural nature that arise during embryonic development. The agents responsible for these disruptions are called teratogens. Teratogens work during certain critical periods of development. In human beings the period of maximum susceptibility to teratogens is between weeks 3-8, this is the period when most organs are forming. Important teratogens are: 1. ALCOHOL: Birth defects in children of alcoholic mothers are called Fetal Alcohol Syndrome (FAS). Babies with FAS are characterized by a. small head size b. Indistinct philtrum c. Narrow vermillion d. Smaller brain size & development Fetal alcohol spectrum disorder (FASD)- physical symptoms of FAS along with behavioral & mental abnormalities. Effect of alcohol on fetus depends on – genetic makeup of fetus, capacity of mother to metabolize alcohol & timing of fetal exposure. FASD is often associated with high levels of alcohol consumption, but animal studies showed that even 2 alcoholic drinks during pregnancy lead to loss of fetal brain cells. Alcohol can cause permanent damage to fetus even before women realize that they are pregnant. 2. RETINOIC ACID In some cases even a compound involved in normal development can act as a teratogen. Retinoic acid (RA) is a vitamin A derivative involved in axis formation, jaw formation, heart formation etc. Its pharmaceutical form, 13-cis-retinoic acid is used to treat severe cystic acne. Deleterious effect of giving large amounts of RA to pregnant animals was known from 1950’s. A group of women who were exposed to RA and chose to continue pregnancy was studied- Of 59 fetus: 26 were born without defects, 12 aborted spontaneously & 21 were born with abnormalities. Abnormalities included: Absent/defective ears Absent/ small jaws Cleft palate Aortic arch abnormalities Thymus defect. CNS defect. Anomalies develop due to defect in neural crest cell migration RA binds to cranial neural crest cells & arrests both their proliferation & migration.  The teratogenic period during which cranial crest cells are affected occurs on days 20- 35 in humans. Glyphosate-herbicides upregulate endogenous production of RA. Eg: Roundup. When Xenopus embryos were exposed to Roundup, cranial neural crest defects & facial disorders were observed. 3. DIETHYLSTILBESTROL(DES) DES is a synthetic female hormone earlier used to prevent miscarriages. Similar to estrogen. It is estimated that in US more than 1 million pregnant women & their fetuses were exposed to DES between 1947 & 1971. Later on it was found the DES has no beneficial effects on pregnancy. DES was banned in1971 when a specific type of tumor was observed in reproductive tract of some women whose mothers took DES during pregnancy. In many cases, DES causes the boundary between oviduct & uterus to be lost, resulting in infertility, low fertility, high risk of reproductive health problems (Cancer of vagina, ectopic pregnancy etc.) 4. BISPHENOL A In the early years of hormone research, steroid hormones were very difficult to isolate, so chemists manufactured synthetic analogs that would accomplish the same tasks. Bisphenol A is one of these analogs and was first synthesized as an estrogenic compound in the 1930’s. Later, polymer chemists realized that BPA could be used in plastic production and today it is one of the top 50 chemicals produced worldwide. Human exposure primarily from BPA that has leached from food containers. Babies and infants acquire BPA through polycarbonate bottles, teenagers and adults get most of their BPA by consuming canned food that has been stored in containers lined with BPA-containing resins. Since 95% of urine samples taken from people in the US and Japan have measurable BPA levels. BPA might cause reproductive failure, cancer, and behavioral anomalies. BPA crosses the human placenta and accumulates in concentrations that alter development in laboratory animals. Indeed women exposed to high levels of BPA during pregnancy had an 83% higher rate of miscarriages than women who had not been heavily exposed. In model organisms, BPA at environmentally relevant concentrations can cause abnormalities in fetal gonads, prostrate enlargement, low sperm counts and behavioral changes when these fetuses become adults. BPA appears to make breast tissue more sensitive to estrogens and it is thought that in utero exposure to BPA may predispose women to breast cancer later in life. 5. THALODOMIDE In 1961 Lenz & Mc Bride independently accumulated evidence that thalidomide a mild sedative used to cure morning sickness in many European countries acts as a teratogen.  It was found to be responsible for the syndrome Phocomelia a condition in which long bones of the limbs are severely deficient thus causing the appendage to resemble a seal flipper (meromelia) or the long bones to be absent (amelia). Over 7000 affected infants were born to women who had taken this drug and a women need to take only one tablet to produce children with all four limbs deformed, other abnormalities include the absence of external ears, heart defects, malformed intestines etc. The drug was withdrawn from the market in November 1961. The drug was found to be teratogenic during days 34 to 50 of pregnancy., 6.NICOTINE Maternal smoking during pregnancy continues to present a major public health concern. Nicotine is extremely harmful to the developing fetus through many different mechanisms and the harms increase with later gestational age at exposure. Women who are heavy smokers are likely to have infants that are smaller than those born to women who do not smoke. High levels of carboxyhemoglobin resulting from smoking appear in the maternal and fetal blood may affect the capacity of the blood to transport oxygen. As a result chronic fetal hypoxia (low oxygen levels) may occur and affect foetal growth and development. Nicotene exposed children tend to have several health problems throughout their lives including impaired function of the endocrine, reproductive, respiratory, cardiovascular, and neurologic systems. Poor academic performance. Behavioral problems like ADHD, and aggressive behaviors. Future substance. Moreover Nicotine interacts with endogenous acetylcholine receptors in the brain and lung and exposure during development interferes with normal neurotransmitter function. 7. HEAVY METALS Industrial pollution has resulted in high concentrations of heavy metals in the environment. Heavy metals like Zinc, lead, and mercury are teratogens. In the former Soviet Union, the unregulated industrial production at all costs approach has left a legacy of soaring birth defect rates. In some regions of Kazakhstan heavy metals are found in high concentration in drinking water, vegetables, and air. In these places nearly half of the people tested have extensive chromosome breakage. In some areas the incidence of birth defects have doubled since 1980’s. Pesticides and organic compounds have caused neurological and behavioural abnormalities in infants whose mothers have ingested them during pregnancy. In 1965, a Japanese firm dumped its mercury into Minamata bay, and methyl mercury was bioaccumulated in fish and shellfish.  When pregnant women ate these fishes in the village of Minamata. This resulted in brain damage and blindness in the babies. This condition was known as Minamata disease. 8. FRACKING CHEMICALS Number of compounds are added to the environment by hydraulic fracturing (procedures used to extract methane from shale) A total of 632 chemicals have been identified as being used in this procedure. It is estimated that about 50% of the fluid used in fracking returns to the surface. Water samples taken from both standing water and groundwater at fracking sites contained estrogenic compounds, antiestrogenic compounds, and antiandrogenic compounds. One of the sites where the water was tested was a ranch before drilling and fracking but ranching had to be discontinued because the animals were no longer producing offspring. A study in Colorado documented an increased incidence of congenital heart disease in children born in families residing close to the fracking wells.