Reexam of EDC-Repro module

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Reexam of EDC-Repro module

  1. If a chemical is shown to cause reproductive toxicity it is generally considered to be of very high concern for human health.

    a) In your own words, briefly define reproductive toxicity. (2p)

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    Reproductive toxicity refers to the harmful effects on the reproductive system caused by exposure to certain substances or environmental factors. It can affect fertility, sexual function, or the ability to conceive and carry a healthy pregnancy. These effects may occur in either parent or the developing offspring.

    b) Give examples of four different reproductive toxicity effects. (2p)

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    1. Reduced Fertility: Chemicals like phthalates or pesticides can impair sperm production or disrupt ovulation, leading to difficulties in conceiving.  

    2. Developmental Toxicity: Exposure to substances like alcohol or certain medications during pregnancy can result in birth defects, growth retardation, or developmental delays in offspring.  

    3. Hormonal Imbalances: Endocrine-disrupting chemicals such as bisphenol A (BPA) can alter hormone levels, impacting reproductive health and function.  

    4. Pregnancy Loss: Exposure to heavy metals like lead or arsenic may increase the risk of miscarriage or stillbirth.

    From ChatGPT

  2. The endocrine system is complex and endocrine disruptors consequently exhibit complex toxicity, which poses challenges to testing and assessment.

    a) Describe two different aspects that make endocrine disruption complex. (2p)

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    1. There are many different hormones and tissues involved in endocrine system which make endocrine disruption complex.
    2. Hormones have maximum effect well below receptor saturation, a very low concentrations can take significant effects.

    b) Which are the main mechanisms by which chemicals can cause endocrine disruption? (2p)

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    1. Hormone receptor agonists and antagonists. For example estrogen receptors (ERα, ERβ) and androgen receptor(AR).
    2. Interfering with synthesis, bioactivation, metabolism and transport of
    hormones. Enzyme induction/inhibition, for example aromatase. Transport proteins, for example

    From slides

    c) Give examples of two different endocrine signaling pathways that play an important role in human reproductive function. (2p)

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    1. Estrogen and androgen signaling pathways
    AR and ERs are important players in sexual and cognitive maturation of the fetal brain. AR and ER⍺ are important for sexual differentiation of the brain. ERβ is important for proper cognitive maturation

    2. Thyroid hormone signaling pathways
    TH bind to TRs and they are essential for proper brain development

    From slides

  3. Hypospadias is a developmental effect that has been shown to be caused by endocrine disruptors in animal studies.

    a) Describe what hypospadias is. (2p)

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    Hypospadias is a condition in which the opening of the urethra is on the underside of the penis instead of at the tip.

    From https://www.mayoclinic.org/diseases-conditions/hypospadias/symptoms-causes/syc-20355148

    b) Which endocrine pathway has probably been disrupted if hypospadias is observed? Briefly describe how this pathway may be disrupted. (2p)

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    Hypospadias is linked to disruptions in the androgen signaling pathway. This disruption, caused by factors like endocrine-disrupting chemicals or genetic abnormalities, impairs testosterone production or action, affecting normal genital development during fetal growth.

    From ChatGPT

  4. The HPG-axis regulates reproduction in humans.

    a) What does “HPG” stand for and what are the three main parts of the HPG-axis? (1.5p)

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    “HPG” stands for the hypothalamic-pituitary-gonadal axis.  

    The three main parts of the HPG-axis are:  
    1. Hypothalamus: Produces gonadotropin-releasing hormone (GnRH).  
    2. Pituitary Gland: Releases luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in response to GnRH.  
    3. Gonads: Ovaries or testes produce sex hormones (estrogen, progesterone, or testosterone) and gametes.

    From ChatGPT after checking with slides

    b) Give an example of an endocrine disrupting effect on female reproduction that may lead to reduced fertility, include which endocrine signaling pathway that is disrupted in this case. (1.5p)

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    An example of an endocrine-disrupting effect on female reproduction is exposure to bisphenol A (BPA), which can disrupt the estrogen signaling pathway. BPA mimics estrogen, binding to estrogen receptors and interfering with normal hormonal signaling. This can impair ovarian function, disrupt the menstrual cycle, and reduce fertility by affecting ovulation or embryo implantation.

    From ChatGPT

  5. Name one hormone receptor that is important for brain development in humans and describe briefly (not in detail) what the consequence for brain development may be if the activation of this receptor is disrupted during a critical window of development. (2p)

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    One important hormone receptor for brain development is the thyroid hormone receptor (THR).  

    If THR activation is disrupted during a critical developmental window, it can lead to impaired brain growth and maturation, resulting in cognitive deficits, reduced IQ, or developmental delays.

    From ChatGPT

  6. Describe one challenge with studying the effects of endocrine disruptors in epidemiological studies, compared to in vivo animal studies. (1p)

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    One challenge in epidemiological studies: It is hard to establish causality due to confounders and reliance on observational data.
    Compared to animal studies: Well controlled environment in vivo animal studies can help us determine a pricise dose-response relationship and causality. However, the results in animal studies cannot fully translate to human as species differences exist. One advantage of epidemiological studies is the direct relevance between human and real-world exposure level.