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neuroendocrine disrupting chemicals Flashcards

1
Q

what is an endocrine disruptor?

A

exogenous substance/mixture that alters the function of the endocrine system and causes adverse health effect

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2
Q

why is DDT bad?

A

it mimics estrogen effects and reduces fertility

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3
Q

what are the effects of EDCs on animals sex and reproduction?

A

changes in sex determination, sexual dysfunctions, changes in mate preference

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4
Q

what is bisphenol A

A

BPA: plasticizer that interferes with sex hormones signaling

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5
Q

what are similarities between hormones and endocrine disruptors?

A

act via hormone receptors, act at low doses, blood levels do not always reflect activity, non-linear dose-response relationships, tissue-specific, timing-specific

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6
Q

differences between hormones and endocrine disruptors

A

EDs:
cause abnormal receptor function, can bioaccumulate, interferes with programming processes

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7
Q

why are fetal exposures to EDC’s most dangerous?

A

change in amount or timing of hormones during featus development can have cause behavior, immune function, neurological, gender development problems

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8
Q

which receptor activity do EDCs interact with

A

nuclear receptors (for steroid hormones)

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9
Q

where in the world are EDCs concentrations in wildlife tissue the highest?

A

in regions of high chemical use (north America) (BDE-209)

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10
Q

what EDCs are good at extinguishing fires? where do we find them most?

A

PFAS / PFOS.
they can not be metabolized.
found in europe and waters most.

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11
Q

name examples of products and the toxic chemical in them

A

body lotion: parabens
cologne: phthalates
bug spray: DEET

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12
Q

how do EDCs affect germ cells and what is the effect on reproduction and sex determination?

A

causes germ-cell re-methylation ->altered testis transcriptome -> spermatogenic defect & epigenetic changes transferred to offspring

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13
Q

what did they conclude when they found testis containing oocytes (vitellogenin) in male fishes?

A

something in the water is oestrogenic

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14
Q

how were starling birds affected by being fed contaminated worms?

A

increased volume of the HVC and more complex songs -> more attractive

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15
Q

7 systems targeted by EDCs

A

immune
reproductive
thyroid
bones
neurodevelopmental
hormone
metabolism

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16
Q

what are organotins? give an example and its effect

A

they are biocides, found in anti-fouling paint. tribytylin is one that increases adipocyte differentiation and adipose tissue amount.

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17
Q

how can BPA affect insulin effect?

A

can affect insulin itself, insulin receptor, downstream compound like P13-kinase, PDK, GLUT4, and affect glucose uptake itself

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18
Q

definition of metabolic syndrome

A

refers to central (abdominal) obesity, insulin resistance, glucose intolerance, dyslipidemia/oxidized low density lipoprotein (LDL), increased triglyceride/reduced high density lipoprotein (HDL) levels, elevated blood pressure, endothelial dysfunctions and atherogenesis

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19
Q

how to EDs contribute to metabolic syndrome?

A

inflammatory processes via cytokines/adipokines and
producing the effects of metabolic imbalance

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20
Q

what are the risk factors of metabolic syndrome?

A

obesity, diabetes, hypertension, decreased HDL, elevated triglyceride levels, hypercoagulable states

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21
Q

what is phthalate?

A

plasticizer

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22
Q

what was DES originally used for? what is it? what were its effects?

A

avoiding miscarriages.
synthetic estrogen.
causes: reproductive malformations, infertility, testicular/vaginal cancers, obesity, metabolic disorders, by causing epigenetic changes during development

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23
Q

where is the organotin compound tributylin found? through what receptor do they act?

A

in agriculture and marine paints.
organotin arePPAR and RXR agonists

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24
Q

more specifically how does tributylin act?

A

inhibits the activity of 11beta-hydroxysteroid dehydrogenase, resulting in an increase in local active glucocorticoids levels.
also inhibits aromatase activity and downregulates ER

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25
how may EDCs cause obesity?
by directly inducing mitochondrial dysfunction
26
EDC-induced changes in adipose tissue can promote what else?
carcinogenesis, by fucking up cell survival signals
27
what is the most affected adipose tissue signaling pathway?
INSULIN pathway
28
how does low dose carcinogen EDCs affect adult stem cells vs uterus stem cells?
tissue-specific adult stem cells -> mutations & epigenetic changes cause tissue-specific tumors. in utero stem cells -> childhood and adult cancer
29
where can we find BPA?
air, soil, water, prepared foods (most largely found synthetic chemical in production)
30
what receptors does BPA bind to?
activates ERalpha and beta and mERs. antagonist to androgen receptors ARs.
31
what happens to BPA in the liver? give example?
it gets transformed through oxidation into metabolites that have worst physiological impact. ex: can affect ERalpha binding affinity
32
what can degrade BPA?
some bacteria, fungi or algae
33
how does BPA affect GR (glucocorticoid R)?
no effect/we don't know
34
what is TDI?
tolerable daily intake (but effects below TDI can still have significant effects)
35
why can't we use toxicological risk assessment in endocrinology? what do we call this?
because high doses don't always have the same effects as low doses. it's not linear (non-monotonic dose response effect)
36
what epigenetic changes can BPA cause?
methylation pattern (hypomethylation), abundance of non-coding RNAs (long and miRNAs)
37
what cancers is early exposure to BPA linked to?
prostate, breast, hepatic cancer
38
how can DNA hypomethylation after BPA exposure be limited?
maternal diet supplemented with methyl donors like folic acid and genistein
39
what is transgenerational transmission?
epigenetic mutations caused by BPA and EDC exposure can cause epigenetic mutations for like 3 generations
40
effects of BPA on brain development
neurogenesis, neuronal migration, gilogenesis, synaptogenesis, apoptosis
41
the 4 highlighted reported effects of low dose BPA
obesity in adults after in utero exposure reversal in brain sexual dimorphism changes in formation of synapses in the brain changes in behavior
42
why are organotin used in anti-fouling paints?
antifugal properties
43
what are organotin's potential adverse effects on animal and human health?
- promotion of reproductive dysfunction - endocrine function disruption (Ex hypothalamo-pituitary axis) - alteration of hormone synthesis and direct damage to endocrine glands - alteration of bioavailability and hormone receptors in target cells
44
where do human get organotin from?
bioaccumulation in fishes!
45
how do EDCs affect thyroid gland?
cause hypothyroidism
46
in what 5 ways can EDCs affect hormones?
synthesis, secretion, transport, binding action, elimination
47
how do pesticides usually affect insect?
they upset larval development by disrupting hormonal activity
48
how are EDCs effects transmitted through generations?
mother uterus -> fetus germline cells -> germline cells used for F2 production -> F3 has no direct EDC exposure
49
how do EDCs increase metabolic disease?
interference with glucose function, insulin function, induce non-alcoholic fatty liver, act as obesogens
50
how can EDCs affect pancreas?
pancreas: loss of beta-cells (produce insulin) which leads to diabetes (involved in metabolic disorder)
51
how do obesogens lead to cardiovascular diseases?
increase obesity -> insulin resistance, glucose intolerance, dyslipidemia -> T2 DM -> CVD
52
how do diabetogens lead to cardiovascular diseases?
hypoinsulinemia, glucose intolerance, insulin resistance, fatty liver, dyslipidemia -> T2 DM -> CDV
53
BPA falls into what categories of EDCs?
obesogens, diabetogens, cardiovascular disruptors
54
name a few obesogenic compounds
phtalates, phenolic ompounds, organotin, dioxins, pesticides, flame retardants
55
how does the immune system in the liver affect metabolic disorders?
kupffer cells; hepatic macrophages; proinflammatory cytokine production; insulin resistance
56
what hormonal receptors is associated with inflammation signaling?
ER alpha
57
which inflammatory compound's activation is undesirable because it leads to apoptosis?
caspase-1. especially bad in hepatocytes
58
how are EDCs and immune system linked to metabolic syndrome?
inflammation. EDCs can induce pro-inflammatory response in all organs
59
what happens to fishes who swim in water contaminated by synthetic estrogen?
there are way more females than males
60
how sensitive to EDCs are kisspeptin receptors?
highly sensitive to early life estrogen exposure! can cause dysfunction in adulthood
61
what does EDCs affecting kisspeptin neurons cause?
affect progesterone peak at the beginning of pregnancy
62
how does EDC exposure turns fetus to female instead of male?
dysruption in anti-muller hormone production by sertoli cell (usually suppresse female mullerian duct cells)
63
what is cryptorchidism? how can it be caused?
when testis don't descend. can be caused by EDCs causing decreased Leydig cell function.
64
what is testicular dysgenesis syndrome?
bunch of problems with testis like cryptorchidism, hypogonadism, reduced semen quality, testicular cancer, hypospadias
65
what is EDC's effect on leydig cells?
cryptorchidism, hypospadias, short AGD, hypogonadism
66
at what 3 levels do EDCs affect sperm quality?
- leydig cell steroidogenesis - t production in sertoli cells - sperm maturation - sertoli cells differentiation
67
6 ways how EDCs reduce male fertility
1. sperm motility/morphology 2. sperm concentration/count 3. DNA integrity 4. steroid action 5. time to pregnancy 6. miscarriage
68
in what steroidogenesis processes can EDCs interfere with?
- mineralocorticoids: aldosterone - glucocorticoid: cortisol - sex hormones: estradiol (can affect every step of the process)
69
what is DES?
synthetic estradiol homolog used to be used for stabilizing pregnancies
70
what are DES effects?
low dose enhances estrogen response, high dose dampens it
71
what is therapeutic width?
dose at which a substance has positive medical effect instead (not toxic)
72
give examples of EDCs effect on the ovary?
- apoptotic oocyte - flattened granulosa cells
73
what cancers can be caused by EDCs?
hormone-dependent cancers (breast, prostate, testicular) in OFFSPRING
74
what hormone has many very similarly structured EDCs?
thyroid (also steroid) (just lacks a hydroxy group)
75
what are EDCs effect on thyroid gland?
hypothyroidism; interferes with production of hormone
76
when does thyroid EDA start forming when exposed to EDCs?
very early: in infants
77
what can happen to adrenal glands when exposed to EDCs?
hypertrophy of adrenal cortex

ANAT322 (10 decks)

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