Chapter 24: Teratogens in Health Flashcards
what is a teratogen
an exogenous agent that causes birth defects
teratogens induces the most damage during the ___ period (weeks 0-8) rather than the ___ period (wks 8-40)
teratogens induces the most damage during the EMBRYONIC period (weeks 0-8) rather than the FETAL period (wks 8-40)
the most organ systems form during ___ period.
embryonic period
what happens if a fetus is exposed to teratogens before week three?
the fetus will either be killed (the mom won’t even know they’re pregnant) or they will be completely normal because the cells are super proliferative and potent– the early fetus can recover.
cyclopamine drug blocks the ___ pathway, resulting in ____
blocks SHH pathway, resulting in cyclopodia.
nicotine as a teratogen
results in impaired brain and lung development
how does zika virus act as a teratogen (what pathways does it act on)
it kills neuroprogenitor cells of cerebral cortex by upregulating MiR9 levels that induce a natural cell death pathway, and downregulates GDNF (reduces stem cell proliferatioN), results in microcephaly.
difference between FAS and FASD
FAS is caused by deficiencies in neural and glial migration (physical changes) due to alcohol. FASD encompasses more symptomes that are present in FAS, and also includes BEHAVIOURAL abnormalities without necessarily including physical changes.
what accounts for the variability in FASD symptoms
1) amount of alcohol 2) time of development the fetus is exposed to alcohol 3) variability in mother’s ability to metabolize ethanol.
two brain structures that are affected in FASD rats
1) no olfactory bulbs form 2) the two hemispheres are not properly separated across the midline, there are abnormalities in the corpus calloseum.
4 ways alcohol affects development
1) affects migration 2) proliferation 3) adhesion 4) survival
why are there abnormalities to the corpus calloseum
because etOH can kill neural crest cells after only 2 hours of exposure. They kill the cells that should form the median aspect of the forebrain and cranial nerves, resulting in a weirdly divided nervous system
3 mechanisms behind alcohol teratogen
1) production of superoxide radicals that damage cell membrane 2) downregulates SHH (required for establishing faical midline). 3) interferes with L1 cell adhesion molecules: usually used to bind cells together or communicate with each other. Mutation in the L1 gene causes syndromes that encompass mental retardation.
physical abnormalities seen in people with RA exposure
absent/defective ears, small jaws, cleft palat, aortic arch anomalies, thymus deficiencies, CNS abnormalities.
reason why physical abnormalities are seen in people with RA overexposure
anomalies are mainly due to the death failure of cranial neural crest cells to migrate into the pharyngeal arches of the face to form the jaws and ears.
mechanism behind RA as a teratogen
exogenous RA exposure (ie due to accutane use) while pregnant results in the activation of the negative feedback pathway that controls endogenous RA. - this suppresses endogenous RA, resulting in RA deficiency, thus SHH DOWNREGULATION, which results in deformation (ex/ of facial features like jaw and ears).
T/F: enxogenous endocrine disruptors result in immediate birth defects
false. they usually cause problems later in life especiialy noticeable during puberty
******4 ways endocrine disruptors interfere with hormone function
1) mimicking natural hormones 2) antagonize or inhibit the binding of hormones to their receptors 3) affects the synthesis,elimination or transportation of hormones 4)primes the organism to be more sensitive to hormones later in life (BPA)
example of how endocrine disruptors interfere with hormone function by mimicking natural hormones.
DES (diethylstilbesterol): it binds to the estrogen receptor to mimic estradiol, skewing reproductive regulation in women
example of how endocrine disruptors interfere with hormone function by antagonizing or inhibiting the binding of hormones to their receptors
VINDOZOLIN (an anti-mold agent). It binds to testosterone receptors and BLOCKS TESTOSTERONE FROM BINDING. It prevents male organ and behaviour differentiation
example of how endocrine disruptors interfere with hormone function by affecting synthesis, elimination or transportation of hormones
ATRAZINE (herbicide) converts testosterone into estrogen, disrupting endocrine function
example of how endocrine disruptors interfere with hormone function by priming the organism to be more sensitive to the hormone
BPA: exposure to BPA in fetal development makes breast tissue more responsive to steroid hormones during puberty.
DES binds to the ____ receptor and mimics ____, and was prescribed to pregnant women to prevent miscarriage. What disease was it seen to cause?
binds to estrogen receptor and mimics estradiol. It was stopped because there was an increase in clear-cell adenocarcinomas in the female reproductive tract
Outline the mechanism of DES and how it affects the female reproductive tract?
DES causes the cells of the mullerian duct (forms the upper vagina, cervix, uterus) to change shape. It destroys the boundary between the oviduct and the uterus, resulting in low fertility. DES also causes transformation of part of the uterus into oviduct tissue, as well as a T-shaped uterus, adenosis of cervix and vagina, and precancerous formation of cells.
Mechanism: DES represses Wnt7a gene expression, resulting in Hoxa10 suppression in the mullerian duct, resulting in disorganized smooth muscle tissue.
Mechanism: DES represses ____ gene expression, resulting in ____ suppression in the ____ duct, resulting in disorganized smooth muscle tissue.
Mechanism: DES represses Wnt7a gene expression, resulting in Hoxa10 suppression in the mullerian duct, resulting in disorganized smooth muscle tissue.
how does BPA affect reproductive health
can cause chromosomal abnormalities or miscarraige by resulting in meiotic defects in oocytes, abnormal ovarian function, aberrant function in follicles.
how does BPA affect males in embryo
BPA exposure in utero can cuase abnormalities in fetal gonads such as prostate enlargement, low sperm counts, low testosterone and bheavioural changes when tehy become adults.
how does BPA reduce fertilizty in female fetuses (4)
1) prevents sex-specific maturation of brain required for ovulation
2) affects alterations in oragnization of uterus, vagina, ovary, breast tissue etc.
3) deficiencies in placenta cause poor fetal growth
4) affets gamete-specific methylation pattern of imprinted genes. (genes gained from mom)
