Peter Snow, Kymmy Hinton, Ashleigh Lambert

BioHorizons eConference 2010

Impacts of chemicals on organism development

The effects of cadmium on foetal organ development in rats and applications as a model organism for humans
Cadmium Ttoxicity (Iintroduction

Cadmium has become one of the most commonly known heavy metals to have toxic effects on the development of humans and animals (Thompson 2008) Cadmium! a toxic trace metal and environmental pollutant! can be found in food! water and also cigarettes ("oyuturk 200#$ "re%cirova 20&0) 't has been reported to be carcinogenic! mutagenic and teratogenic! and has the ability to accumulate in human tissues ("oyuturk 200#)

Peter Snow, Kymmy Hinton, Ashleigh Lambert

The half( life of Cadmium within the human body has been shown to be approximately #) to &28 days (fast component) and # * to 2+ 0 years (slow component)! which has led to the deleterious effects of cumulative exposure to the metal (Thompson 2008) The long half life of the metal makes prolonged exposure particularly dangerous! due to the cumulative effects of the toxin within an organism (Thompson 2008) The long lasting effects of Cadmium in the body have been linked to severe shown to have severe health concerns! such as,, due to accumulation through intracellular renal tubule cells (Thompson 2008)

Cadmium !"sorption

The liver is the predominant target for Cadmium absorption! due to the accumulation within this organ-s e tissue from through exposure in the diet ("oyuturk 200#) .cute and chronic poisoning with Cadmium has been shown to be potentially ha/ardous to health (e g 0000) ("oyuturk 200#) Cadmium has been shown to have several teratogenic effects on experimental populations of laboratory rats! leading to skeletal and visceral malformations and other abnormalities ("re%cirova 20&0$ Thompson 2008) 1isceral malformations occurred mainly in liver tissue cells! whereich the absorption and accumulation of this metal depend on sex! age and physical health ("re%cirova 20&0) 2prague 3awley rats have been commonly used as experimental test sub%ects for modelling human genetics (Campbell 2004) 5ats have been and continue to be the main experimental model for human(related genetic research (Campbell 2004)

Teratogenic effects of Cadmium

2evere teratogenic effects caused by Cadmium exposure and resulting foetal malformations
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Peter Snow, Kymmy Hinton, Ashleigh Lambert

can also be associated with the accumulation of Cadmium into the germ lines of rats (Thompson 2008) .ccumulation of Cadmium was found to occur in male testis and liver cells (Thompson 2008) with Cadmium integration into spermatocytes and spermatogonia chromatin reducinges cell count for these cells and also reduces fertility of sperm (Thompson 2008) 5ats with Cadmium exposure showed increased rates of abnormal sperm morphology and higher infertility rates (Thompson 2008) .dministration of 6inc to affected rats showed a reversion in the anomalies (Thompson 2008) Cadmium exposure was shown to cause anovulation within rat female sexual organs! during the menstrual cycle (Thompson 2008) .novulation also has been shown to be associated with lower progesterone levels and ovarian haemorrhaging due to the interference on hormones that control sexual development (Thompson 2008) This has highlighted some of the potential effects that Cadmium has on growing organisms! which shows evidence of the teratogenic and mutagenic effects of the metal

!ntioxidants and prevention of teratogenic effects

"oyuturk (in 200#) performed an experiment withcompared rats in two treatment groups over eight days! to investigate the effects of anti(oxidants on cadmium toxicity 7ne group were sub%ected to 2mg8kg8day of CdCl2! whilst rats treated with Cadmium and anti(oxidants were given 2mg8kg8day of CdCl2 and anti(oxidant doses of sodium selenate (0 2)mg8kg8day)! 1itamin C (2)0mg8kg8day) and 1itamin 9 (2)0mg8kg8day) ("oyuturk 200#) 5esults showed rats exposed to Cadmium exhibited degenerative changes! including hemorrhagic legions! hyperaemia! picnotic nuclei! sinusoidal dilation! vacuoli/ation and big granules in hepatocytes ("oyuturk 200#) .s cCadmium enhances the production of reactive oxygen species! thereby resulting in
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Peter Snow, Kymmy Hinton, Ashleigh Lambert

increased lipid peroxidation! enhanced damage to 3:. and membrane structure! altered gene expression and proliferation of cells ("oyuturk 200#) 5ats exposed to Cadmium who were treated with anti(oxidants were shown to exhibit decreased levels of liver alanine! glutathione! serum aspartate and lipid peroxidation ("oyuturk 200#) The co(ordinated interaction of anti(oxidants to break radical chains is vital in protection against free radical damage ("oyuturk 200#) .nti(oxidants proved beneficial in reversing Cadmium toxicity because they are involved in fundamental homeostatic and metabolic processes! which reversed the deleterious effects Cadmium hads on hormonal and en/ymatic function ("oyuturk 200#)

#utations and other foetal damage due to Cadmium exposure

The predominant phenotypic malformations that arose from Cadmium exposure were cleft palates! organ malformations and hormonal interference regarding sexual development (Thompson 2008$ "re%cirova 20&0) The main concerns with Cadmium on foetuses were failure of implantation of the embryo! and a wide range of anomalies caused by exposure at specific developmental stages of embryogenesis (Thompson 2008) .nomalies to organ tissues within rats included hypoplasic and deformed veins! which are known to be a serious health concern due to alteration in structure and function in the affected organs ("re%cirova 20&0) 'ncidences of pathological processes in later stages of pregnancy and in the early postnatal period! causing third trimester complications and minor but significant problems in the offspring of the exposed individuals were also reported (Thompson 2008) Testicular anomalies were observed! such as disruption to blood(testis barrier! leading to reduced germ cell numbers! and ultimately infertility (Thompson 2008) 9xperimental results showed that rats in%ected with a large dose of CdCl2 showed pronounced oedema and testicular
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Peter Snow, Kymmy Hinton, Ashleigh Lambert

haemorrhage two hours after treatment (Thompson 2008) ;idespread necrosis was observed at higher dosages of Cadmium (Thompson 2008)

$elation of Cadmium as a teratogen on rats to human development

Cadmium in mammals has been shown to alter 3:. structure! which results in the metal integrated within the chromatin of both humans and rats! which has been known to cause membrane and oxidative damage ("oyuturk 200#$ "re%cirova 20&0 ) 2imilar effects have been found in humans and rats! with human maternal intake of Cadmium through smoking and consumption in diet (Thompson 2008) caused foetal damage and malformations ("re%cirova 20&0$ Thompson 2008) The seriousness of Cadmium exposure in humans has shown similar visceral malformations due to the altered chromatin and deleterious effects on en/ymes and sexual development ("re%cirova 20&0) .dditionally! cCadmium has been shown to interfere with ribosomal structure! which leads toleading to a lack of function of the ribosome as found by( "re%cirova et al. (20&0)

%udgement& 'valuation of research& and implications for society

.lthough! e9xtensive evidence has illustrated the deleterious effects of Cadmium as both a teratogen and a toxic chemical! some evidence was present that indicatedd that degenerative changes in rat foetuses were not associated to the intake of Cadmium ("re%cirova 20&0) These were inconsistent with previous findings and overwhelming evidence that have illustrated the teratogenic effects of Cadmium

'ncidences of foetal miscarriage in humans have been shown to occur from exposure to
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Peter Snow, Kymmy Hinton, Ashleigh Lambert

Cadmium dosages ranging from twenty(five2) to thirty(eight<8 micro(litresu= at minimum (Thompson 2008$ "re%cirova 20&0) :egative effects that have occurred as a result of Cadmium exposure to pregnant women and rats included placental necrosis! inhibition of blastocyst growth and competition with 6inc to be integrated into the body (Thompson 2008$ "re%cirova 20&0) .ccumulation in foetuses has been shown to occur from the second division of a /ygote! at the four cell stage onward! leading to rapid accumulation within a developing foetus (Thompson 2008$ "re%cirova 20&0) Cell adhesion was also lost as well as greater occurrences of apoptosis in foetal growth which lead to degeneration and subse>uent loss of the foetus (Thompson 2008$ "re%cirova 20&0)

The evidence present in the findings proved demonstrated consistent with the claim that Cadmium had teratogenic effects on rat foetal development The presence of Cadmium in the liver was associated and caused by the toxic effects of the heavy metal! which resulted in many visceral anomalies and foetal death (Thompson 2008) 5esearch found that hepatocytes around blood vessels within the liver were the first cells to have contact with the heavy metal and had shown the highest concentrations of the metal ("oyuturk 200#)

The severe teratogenic effects of Cadmium have affected both rat and human foetal development! development of sexual organs and produced reproductive anomalies in both males and females 9xposure to Cadmium has been shown to severely affect developing embryos and also have deleterious effects on both male and female germ lines! resulting in infertility and foetal malformations The effects that may result in human exposure to Cadmium illustrate the need for proper containment of the metal and prevention of contamination into food supplies! as well as testing for its presence in soil where food products may potentially be grown The overall findings highlighted the main effects
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Peter Snow, Kymmy Hinton, Ashleigh Lambert

Cadmium has shown to haveas a mutagenic effects in association to the teratogenic effects already found

The toxicity of Cadmium in minute amounts and after brief exposurein short exposure times times make it a substance re>uiring great caution C! considering its prolonged half(life! which it has the gives rise to potential for ongoing cumulative effects .s a result! testing for the presence of Cadmium in food and water products! such a fish oils for human consumption! has become necessary to avoid exposure to this ha/ardous substance ?ope exists in the treatment of Cadmium toxicity with powerful anti(oxidants! and 6inc to counteract damage done that has occurred on exposed to reproductive cells @urther studies in this area on other organisms involving longer exposure periods may provide invaluable data to researchers wishing to provide a solution to the toxic effects of Cadmium in humans

$eferences Campbell! 5eece! Aeyers! Brry! Cain! ;asserman! et al (2004) Ciology! 9ighth edition .ustralian version

"oyuturk! A! Danardag! 5! Colkent! 2! Tunali! 2 (200#) The potential role of combined anti( oxidants against Cadmium toxicity on liver of rats

"re%cirova! = ! =auschova! ' ! Ci/ek! E (20&0) 3istribution of ?eavy Aetals in the =iver of @oetuses and @emale Aice after 7ral .dministration during Eregnancy ( a ?istochemical 2tudy .CT. 19T C5:7! #4F 22)(2<&

Peter Snow, Kymmy Hinton, Ashleigh Lambert

Thompson! G! Cannigan! G (2008) CadmiumF Toxic effects on the reproductive system and the embryo

Bniversity of Hueensland (20&0) C'7= &0*0 =ecture Aaterial

Dap! . (20&0) C'7= &0*0 Ciohori/ons 9(conference Elenary =ecture