PHY3181 Lecture Notes - Seminiferous Tubule, Prostate Cancer, Cytokinesis
4 Jun 2018
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Week 9. Endocrine Disruptors and Assisted
Reproductive Technology
ENDOCRINE DISRUPTORS AND REPRODUCTION
• Option as an essay question in exam
Learning objectives:
• Short and long-term effects of EDCs
– Clover disease
– Epigenetics
– EDCs:
▫ Phthalates
▫ Vinclozalin
▫ BPA ad othe Bispheols
• Endocrine disruptor chemicals:
o Plant steroids:
▫ (phytoestrogens) – particularly in clovers
o Components of detergent:
▫ (alkylphenoxylates and their derivatives)
o Compounds leached from plastics:
▫ (BPA, Nonylphenol and Pthalates)
o Certain pesticides/fungacides:
▫ (DDT, Atrazine, and vinclozline)
o Polychlorinated chemicals from industry:
▫ (dioxins, polychlorinated bisphenols)
• EDCs:
o Impacts of EDCs are complex and subtle
o Almost impossible to prove that any particular EDC is causing biological changes
o Instead of a few highly dangerous chemicals, EDCs may combine tiny effects to harm
human health
o Cardiovascular diseases, Type 2 diabetes, obesity, thyroid disorders, cancer
• Problems with EDC research:
o How do low-level normal exposure to a foetus or infant cause changes in the endocrine
system that plays out later in life?
o Most sensitive time for a person (susceptibility) is whilst developing – foetal period and
first 2 tears of life – effets aet ofte see util ell ito adulthood
o Connection in humans is difficult because:
▫ Time lag is so great
▫ Exposure is difficult to measure
▫ Exact role of certain hormones is not fully defined so changes in activity are hard
to assess
▫ Some are antiandrogens, some stimulate Era, some block ERb (very challenging)
find more resources at oneclass.com
find more resources at oneclass.com
• Toxicology:
o Much more clear cut
o Study of doses – medical theory that chemicals only cause harm when they exceed a
certain level
▫ Looking at low dose effects of EDC
▫ Low doses cause effects
▫ Opposite effects at low and high doses
o The issue of dose response relationships is perhaps the most controversial issue
regarding EDCs
▫ Linear – monotonic or biphasic (EDCs are bell curved, not linear)
o Debate = climate change
▫ Opinion or speculation vs evidence
▫ Science remains too uncertain for government action
• EDCs ee disoeed Austalia Agiultual “ietists i the 9s
-> sheep were eating clovers
-> identified problems
• Chemical structure of phytoestrogens:
o Cloes aet odia gass -> packed with phytoestrogens
o Phytoestrogens activate estrogen receptors at a great degree (is an EDC)
o Sold at pharmacies for menopause
o Can have detrimental effects if you take them at the wrong time
• Clover disease disrupts reproduction:
(Short term effects)
o Female Ewes:
▫ Prolapse of the uterus
▫ Dystokia (difficulty lambing)
▫ Altered cervical function
▫ Latatio at latate
o Male whethers:
▫ Swollen bulbourethral glands
▫ Blocked urethral
▫ Impairs spem transport
o Imbalance of endocrine signalling
o Direct exposure during adulthood
find more resources at oneclass.com
find more resources at oneclass.com
• Declining fertility in clover ewes:
(long term effects)
o Over time litters decreased in number and size
o Even after clover was removed, changes in reproductive capacity was permanent
o Not just a direct effect, also indirect
o Permanent infertility general occurs with chronic exposure to estrogen clover (2 years +)
• Clover disease is an example of severe endocrine disruption
• Exposure to EDCs has greatest effect on foetal/neonatal development
• Epigenetics:
o EDCs are relayed through generations via epigenetics
o Effects on a single generation can be relayed through multiple generations
o Epigeetis = upo the geoe
-> control on DNA that happens above genome
-> epigenetic modifications = changes the way DNA is read
o Epigenetic modification involves change to DNA and histone resulting in altered activity
(enhanced or silencing) but do NOT change gene sequences
o Eg. Cloned cat
▫ Even though DNA is exactly the same, there will be different genetics due to
epigenetics
o EDCs cause epigenetic changes that translate across a number of generations
o Multiple generations may be affected by experiences during pregnancy either because
several generations are exposed at the same time or because it is truly inherited
o When pregnant female is exposed it may directly affect her (F0 generation), her child
(F1) and even her grandchildren (F2)
o A ales spe a also e effeted a eposue ad affetig his hild
(transgenerational effects may emerge in later generations)
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Endocrine disruptors and reproduction: option as an essay question in exam. Learning objectives: short and long-term effects of edcs. Impacts of edcs are complex and subtle: almost impossible to prove that any particular edc is causing biological changes. Exact role of certain hormones is not fully defined so changes in activity are hard to assess. Some are antiandrogens, some stimulate era, some block erb (very challenging: toxicology, much more clear cut, study of doses medical theory that chemicals only cause harm when they exceed a certain level. Looking at low dose effects of edc. Opposite effects at low and high doses: the issue of dose response relationships is perhaps the most controversial issue regarding edcs. Linear monotonic or biphasic (edcs are bell curved, not linear: debate = climate change. Science remains too uncertain for government action: edcs (cid:449)e(cid:396)e dis(cid:272)o(cid:448)e(cid:396)ed (cid:271)(cid:455) aust(cid:396)alia(cid:374) ag(cid:396)i(cid:272)ultu(cid:396)al (cid:272)ie(cid:374)tists i(cid:374) the (cid:1005)9(cid:1008)(cid:1004)(cid:859)s. > control on dna that happens above genome.
