Reproductive Toxicology Flashcards
How many couples suffer from infertility and why?
15% and it can be either the males, females or unexplained causes
Are sperm numbers declining?
Yes
Has the female fertility rate decreased?
Yes
What causes the reduction of fertility?
Social and economic changes,
Lifestyle choices
Genetics
What is reproductive toxicity?
Adverse effects on any aspect of: - male/female reproductive structures function
- the developing offspring
- lactation which interferes with normal offspring development
What are potential targets for reproductive toxicants?
Gametogenesis
Release of games
Zygote formation
Embryonic/fetal development
Parturition
Lactation
How do you identify what a reproductive toxicant is?
- clinical workups of people in infertility clinics
- people undergoing drug treatments e.g chemo
Epidemiological studies on the general populations e.g. workers using chemicals - Animal studies
What is the aim of repro tox studies?
reveal an effect of a substance on mammalian reproduction through looking at reproductive competence, the developing embryo or fetus prior to birth and monitoring the development of any offspring
How would you detect immediate as well as latent effects?
Observations should continue through one complete lifecycle
How is repro tox studied (e.g. experiment)?
In vitro - carried out in a petri dish e.g. grow cells and tissues derived from the living organisms
In vivo - carried out on live animals or human tissue
What are advantages of in vivo studies?
- most accurately depict the real life situation
- picks up on repro tract/HPG axis
- Metabolism of drugs can be considered
- Effective
- Can be used to study transgenerational efffects
What are disadvantages of in vivo studies?
-Time consuming
-Costly
-Compounds can persist in animal long after exposute
-Requires more animal procedures than in vitro
-Prenatal testing requires exposure to the mother (who might not be of interest in the study)
What are advantages of in vitro studies? (theres lots of these)
- cheaper
- rapid/high throughput
- no drug administration to animals
- insight into tissue were in vivo is unethical or impractical
- permits investigation into drugs affect directly the gonads
- Look into specific cell type
- highly controlled
Easy to manipulate culture conditions - Allows for examination of cell-signalling
- Allows examination of a specific follicle type or stage
What are disadvantages of in vitro studies?
- Doesn’t tell the whole story and in vivo studies need to confirm this
- There might be some tissue level barriers limiting or preventing drug exposure
- no metabolism of drugs
- doesn’t recapsulate cellular pathways that occur in vivo
- excludes repro effects that occur through HPC axis
What is usually used to study repro tox?
Animal models (should be mammal e.g. rats)
For embryonic studies only what do you use?
A second mammalian species (usually rabbit)
Are man made and natural toxicants just as bad for you?
Yes - arsenic is natural
What are repro tox groups?
- Recreational drugs
- Animal toxins
- Endocrine disrupting compounds
- Pesticides
- physical agents
- naturally occuring
- pharma drugs
- heavy metals
- plant toxins
- occupational chemicals
- biological agents
What are the side affects of the repro tox chemo?
Hair loss
tiredness
sick
risk of premature ovarian insufficiency (POI) and infertility
What percentage does fertility rate reduce to in women after having cancer?
38%
Does chemo reduce the size of the follicle pool causing early menopause?
Yes
How does chemo affect the ovary? what does it cause?
Germ cell loss
Direct loss of PM
PMF activation
Accelerate atresia
Inflammation
Stromal damage
Vascularisation
How does chemo cause reduced fertiltiy?
Chemo targets rapidly developing tumour cells.
The primordial pool rests in a dormant protected phase until the oocyte enters the growing population.
The tumour protein p63 is expressed in dormant and growing oocytes and radiation causes germ cell death through upregulation of this. This can also be upregulated due to damage
How do recreational drugs cause a reduction in fertility? - cigarettes - the odds of fertility
- Accelerates menopause by 1-4 years
- Odds of female smokers conceiving naturally are 80% of a non smoker
- Odds of a smoker conceiving in IVF is 66%
- Higher risk of miscarriage and live birth
What experimental study was done to look into smoking and fertility? (MICE)
Study 1 - mice exposed to two cigarettes daily for 8 weeks
Study 2 - mice exposed to cigarette smoke twice a day for 60 mins 5x per week for 12-18 weeks
What was the results of the mice smoking study?
Decreased follicles in both studies - mainly early transitional and primordial follicles
What are endocrine disrupting chemicals?
These are chemicals that mimic, block or interfere with hormones in the body’s endocrine system.
Can increase the risk of cancer and repro impairment
How does endocrine disruption work?
The endocrine blockers bind to the normal endocrine signal and either block completely the response or cause a different type of response e.g its over/under response
Endocrine disrupting chemical example - how did BPA work?
Found in packaging, dental sealants ect. and enters body through inhalation, skin and digestion. Has a weak estrogenic, anti-androgenic and anti-thyroid activities and can accumulate in tissues
What did a mice study of BPA show?
Can reduce testosterone
What did the BPA human tissue study show?
No testosterone difference
Has BPA been banned?
Yes but has been replaced by chemicals we don’t know anything about
What do scientists need to consider when testing repro tox?
- Epidemiological vs experimental studies
- Species used
- Development stage studies
- Type of exposure
Experimental techniques used
Long term vs. short term affects
