Reproductive Tox Flashcards
What is developmental toxicity?
an alteration in the structure or function of a developing embryo, fetus, infant, child, or adult resulting from an exposure to the male or female either before or after conception or during development.
What is the portion of women in the labor force today?
> 75% of women in reproductive age are employed outside home.
What is the rate of human reproduction?
100-250/1000 (conception)
How many testis are there and what is their function?
2,production of sperm and hormone
What is the Epididymis?
there are two and it is the sperm maturation, sperm storage.
What are the Vas Deferens and how many are there?
2, rapid transport of sperm
What is the ejaculatory duct and how many are there?
2, conduction of sperm
What is the penis used for?
sperm delivery
How many seminal vesicles are there and what is it used for?
2, secretion, large portion of semen.
What is the prostate gland used for?
secretion, large portion of semen.
What is the bulbo-urethral gland used for?
secretion, large portion of semen.
What are the ovaries?
oocyte production, sex hormone production.
What are the oviducts?
Conduction of oocyte form ovary to uterus.
What is the uterus?
chamber in which new individual develops.
What is the cervix?
secretes mucus that enhances sperm movement into uterus, and after fertilization reduces the embryo’s risk of bacterial infection.
What is the vagina?
receive sperm, birth canal
What are the 3 facts for successful Reproduction (Must know)?
- Numbers and quality of sperm.
- A healthy oocyte.
- A successful implantation (uterus, hormones)
The gonad produces Androgens in males what does this aid in development?
penis, pubic hair , and testes.
The gonad produces estrogen in females what does this lead into for development?
development of breasts, ovaries, and uterus.
The adrenal cortex in females and males lead to the development of what?
pubic hair, armpit hair, and acne.
What hormone does the hypothalamus control in males reproductive function?
gonadotropin-releasing hormone GnRH.
What reproductive hormone does the hypothalamus control in females?
GnRH gonadotropin-releasing hormone.
What does the anterior pituitary (gonadotropins) control in both female and male reproductive functions?
LH and FSH (Lutenizing hormone, and follicle-stimulating hormone)
What do direct acting gonadotoxicants mimic?
endogenous molecules
When direct acting gonadotoxicants mimic endogenous molecules, what does it disrupt?
reproductive control process- a feedback system.
What blocks the binding of hormones to receptors?
The direct acting of gonadotoxicants that mimi endogenous molecules
What does the direct acting gonadotoxicants that mimic endogenous molecules alter?
the effect of hormones on target tissue hormone analogs.
What cause direct cytotoxicity?
direct acting gonadotoxicants.
When direct acting gonadotoxicants cause direct cytotoxicity what does it affect?
the production of sperm and oocytes.
What are some direct cytotoxicity gonadotoxicants?
alkylating agents, toxic metals.
What is cadnium and what does it do?
acts as a direct acting gonadotoxicant that produces direct cytotoxicity and will damage the functions of sex accessory organs.
What does indirect acting gonadotoxicants that cause metabolic activation form?
chemically more reactive metabolites.
What can potentially mimic endogenous molecules?
indirect acting gonadotoxicants that cause metabolic activation.
What are Salicylazosulfapyridine, 2-ME
Reactive metabolites formed from indirect acting gonadotoxicants that cause metabolic activation.
What do indirect acting gonadotoxicants that disrupts homeostasis impair?
synthesis, secretion, and clearance of hormones.
What are examples of indirect acting gonadotoxicants that disrupt homeostasis and impair synthesis, secretion, and clearance of hormones?
DDT, Polychlorinated biphenyls.
What does indirect acting gonadotoxicants that disrupt homeostasis alter?
plasma protein binding of hormones.
What are some examples of indirect acting gonadotoxicants that disrupt homeostasis that alter plasma protein binding of hromones?
cyproterone, flutamide
What do indirect acting gonadotoxicants that disrupt homeostasis modify?
the activity of hepatic enzymes that eliminate sex hormones.
What are examples of indirect acting gonadotoxicants that disrupt homeostasis, that modify the activity of hepatic enzymes that eliminate sex hormones?
P450 inducer/inhibitor.
What are indirect acting gonadotoxicants that cause drug induced impotence affect?
neuroendopcrine processes involved in erection and ejaculation.
What are examples of indirect acting gonadotoxicants that cause drug-induced impotence?
ethanol, clonidine.
What is special about alligators and florida and why?
abnormally small penises and low testosterone levels.
Which country has one of the highest sperm counts?
American Students
Which state in the US has the lowest concentration of low sperm count?
Missouri
What are indirect exposure in baby boys to estrogen like toxicants?
Mothers milk is a pollutants in body fat enter the blood and milk during pregnancy and lactation.
What are the two compartments of the testes?
the seminiferous tubules and the interstitial tissue.
What do the seminiferous tubules do?
produce and transport sperm
What do interstitial tissue do?
Transport of nutrients and production of testosterone.
The testes has a blood testis barrier between where?
the interstitial capillary and seminiferous tubule
What does the blood-testis barrier prevent?
toxicants from entering seminiferous tubule.
What is not fully developed until puberty in males?
the blood testis barrier.
What are the cell types in the seminiferous tubules?
spermatogonia, spermatocytes, sperm, sertoli cells.
What are spermatogonia cells responsible for?
stem cells mitotically active
What are spermatocytes responsible for?
under or after mitosis and meiosis.
What is sperm responsible for?
the final stage of spermatogenesis
What are the responsibility of sertoli cells?
Act as nurse cells in the seminiferous tubules.
What cells do the interstitial tissue consist of?
Leydig cells
What are leydig cells responsible for?
secrete male sex hormones.
What is the functional unit of the testes?
seminiferous tubule
What in males requires 74 days?
the process of spermatogenesis
How long does the process of spermatogenesis in humans require?
74 days
Where does the sperm get mature in?
Epididymis
What is the normal standard volume of semen stated by the WHO?
2-5 mL
What is the normal sperm count number stated by the WHO?
20million/mL
What is the normal sperm motility set by the WHO?
50% Progressive motility
What is the normal sperm morphology indicated by the WHO?
30% normal morphology
What are the consequences when the male spermatogonia is targeted?
Decreased fertility, decreased permanent sterility
If the consequences are decreased fertility and permanent sterility what is the target?
spermatogonia
What are toxins that will target the spermatogonia?
procarbazine and busulfan
What is the target for procarbazine and busulfan?
spermatogonia
What are the consequences when the spermatocytes are targeted by toxins?
decreased fertility
Are the consequences on the spermatocytes reversible or irreversible?
reversible
What are toxins that target the spermatocytes?
2-methyloxyethanol and procarbazine
What does 2-methyloxyethanol and procarbazine target?
The spermatocytes
What are the consequuences when the spermatids are targeted by toxins?
Decreased fertility
When the spermatids are targeted by toxins is it reversible or irreversible?
Reversible
What are toxins that target spermatids?
Methyl chloride, SASP, Imidazoles.
What do SASP, methyl chloride, and imidazole target?
The spermatids.
What are the consequences when the sertoli cells are targeted by toxins?
Spermicide, permanent sterility
Spermicide/ permanent sterility can be consequences from what targets?
spermatogonia and sertoli cells.
What are examples of toxins that target sertoli cells?
boric acid and dinitrobenzene
What does Boric acid and Dinitrobenzene target?
sertoli cells.
What are the consquences when Leydig cells are targeted by toxins?
Testosterone depletion
What target has the consequences of testosterone depletion?
Leydig Cells
What are examples of chemicals that target leydig cells?
Ethane and Lead
Ethan and Lead target what cells?
Leydig cells
What are the consequences when Epididymis cells are targeted?
delayed sperm maturations, decreased motility and decreased fertility
What toxins target the epididymis?
SASP and Chlorohydrin.
2-ME induced infertility acts in what?
Spermatocytes; Spermatogonia can be seen; it is irreversible
What does Boric Acid induced sterility do?
Injure sertoli cells; permanent sterility.
What is the route for dibromochoropropane that is >3ppm?
inhilation subcutaneous
What does dibromochloropropane at greater than 3ppm cause toxicity in?
Seminiferous tubule atrophy
at a dose greater than 25 ppm what does hexaclorocyclohexane affect?
seminiferous tubule atrophy
What is the route for hexachlorocyclohexane greater than 25 ppm?
DIET
Chloroprene (Kepone) greater than 50 ppm causes what?
testicular atrophy
What is the route for chloroprene?
In diet
What do PCBs cause at about 50-100ppm?
decreased spermatogenic fertility
PCB’s route is where?
diet
Increased testosterone secretion will inhibit what?
LH secretion through its negative effect on hypothalamic GnRH
An inhibitory signal from Sertoli cells influences what?
GnRH and FSH secretions
What are the consequences when toxins act on CNS pathways to alter hypothalamic-pituitary control of gonadotropins?
decrease in libido, impotence, inability to ejaculate, testicular swelling, and gynecomastia.
What are some general examples of toxins that act on CNS pathway to alter hypothalamic-pituitary control of gonadotropins?
Marijuana, Narcotics, Alcohol.
What are inhibitory toxins that act on the CNS pathway to alter hypothalamic-pituitary control of gonadotropins?
Anesthetics, anagesia, sedatives, and tranquilizers.
What are some excitatory toxins that act on the CNS pathways to alter hypothalamic-pituitary control of gonadotropins?
anitdepressants, stimulants, and hallucinogens.
What are consequences of toxins that act on hypothalamus and/or pituitary to disturb the normal feedback control mechanism?
They alter the systemic level of GnRH, FSH, LH, and testosterone.
What are examples of toxins that act on the hypothalamus and or pituitary to disturb the normal feedback control mechanism?
DES: Diethylstilbestrol
What is reproductive toxicity?
a delay in pregnancy, an increase in early pregnancy loss, or sub-fertility or absolute infertility resulting from an exposure to a physical, biological or chemical agent that laters the reproductive performance of either partner.
What happened to the young rats when treated with PCB’s ( PTU)?
Grow extra large testes and produce more sperm
What was found in RATS that PTU mimics?
Mimics thyroxine
What is important to know about thyroxine and the importance of PTU mimicking it?
It inhibits sertoli cell proliferation under normal testes development.
What does PTU reduce?
Thyroxine levels
What happens when PTU reduces thyroxine levels?
allows sertoli cells to proliferate abnormally
What are the symptoms of PCB induced male reproductive toxicity?
Hypothalamic dysfunction, less GnRH, less androgen, fat accumulation, and smaller sex organ.
What does PCB induced male reproductive toxicity produce?
pituitary tumor, high FSH, LH, high androgen, and larger sex organ.
What will metabolize the cGMP?
PDE5: cGMP-specific phosphodiesterase type 5
What is Vinclozolin?
A fungicide mimics testerone
What are the side effects of vinclozolin?
severe erection damage due mainly to the systemic effect rather than on urethral.
What is clonidine?
A drug induced impotency
What is emission?
movement of semen into the urethral
What is ejaculation?
Propulsion of the semen at the time of orgasm
What two processes involve muscle contraction and spinal reflex?
Emission and Ejaculation.
What does ethanol do to the penis?
Ejaculation difficulty
What do organosphosphates affect?
Neuroendocrine process.
What occurs when organophosphates affect neuroendocrine processes?
It diminishes the ability to ejaculate.
What does lead do to the penis?
Decreases sperm counts.
What are the 3 compartments of the ovary?
Follicles, Corpus Luteum, Interstitial tissue.
What is the function of the follicles?
Manufacture oocytes and produce estrogen.
What is the function of the Corpus Luteum?
Act as a temporary endocrine gland.
What is the function of the Interstitial tissue?
Transport of nutrients.
Does the ovary have a barrier?
no effective blood ovary barrier
What type of barrier is produced when a female is pregnant?
a blood placenta barrier
What does the blood placenta barrier exclude?
Materials with MW> 1000.
What are the three cell types in the ovary?
Oocytes, Granulosa cells, and Corpus Luteum
How many oocytes are there at the time of birth?
2million
How many oocytes are there at puberty?
300,000
How many oocytes become mature?
400 become mature, one at a time.
What do granulosa cells support?
the oocyte in the follicle
What do the granulosa cells synthesize?
Hormones
What is the corpus luteum responsible for?
collapsed follicle following ovulation and to produce progesterone.
What does the ZG (Zona granulosa) produce?
Estrogen
What are the Thecal Cells?
Provide the androgenic precursors for estrogens synthesized by the granulosa cells.
What occurs in the Graafian Follice and Secondary Oocyte?
The firwst meiotic division is completed just before ovulation.
When does the Follicular phase occur?
Days 1-13
What phase does this event belong to : Menstruation, endometrium breaks down.
Follicular Phase
What phase does this belong to: Low level of estrogen and progesterone?
Follicular phase
What phase does this occur in: Follicle maturs in the ovary, endometrium rebuilds?
Follicular phase
What day does this occur: Follicle matures in ovary, endometrium rebuilds?
days 6-13
What phase does this event occur: Estrogen increases with the growth of the follicle?
Follicular phase
What day does ovulation occur?
Day 14
What phase is this when the secondary oocyte is released?
Ovulation
What phase is when progesterone starts to increase?
Ovulation
What day does the luteal phase start?
Day 15-28
What phase is this when the corpus luteum forms, endometrium thickens and develops?
Luteal phase
What is the last event of the luteal phase?
Change of progesterone follows the fate of corpus luteum.
When LH triggers the follicle to be disrupted what is occurring with the estrogen?
estrogen secretion by cells of the follicle slows down.
What occurs within the follicle once LH triggers the follicle?
Meiosis 1 resumes in the primary oocytes and a secondary oocyte occurs.
Why does the follicle rupture?
LH stimulates the production of lytic enzymes that act on the follicle where it balloons out from the ovary.
High levels of LH trigger what?
Ovulation
When LH ruptures the follicle the follicle parts left behind are transformed into what?
corpus luteum
What does the Corpus Luteum that is transformed starts secreting?
quantities of progesterone and estrogen.
What are cytotoxic effects on the ovary?
Germ cell killing
What are agents that cause cytotoxic effects on the ovary?
Radiation, Alkylating agents, and PAH
What is impaired when toxins impair reproductive tract?
disruption of the cervix function.
What are things that disrupt the cervix function?
oral contraceptives and DES
What is altered when the reproductive tract is impaired?
the vaginal flora.
What causes the vaginal flora to be altered?
Vaginal tampons
What toxins that impair the reproductive tract causing placental malfunction?
Cadmium
When toxins interfere with sex hormone regulation what does it affect?
neuroendocrine neurons to decrease libido and inhibit secretion of gonadotropins.
What are agents that affect the neuroendocrine neurons that interfere with sex hormone regulation system?
reserpine and chlorpromazine.
What occurs when toxins interfere sex hormone regulation system such as DDT and Kepone?
competitively inhibit the binding of estrogen to its receptor.
What do barbiturates and insecticides disrupt?
disrupts the biotransformation process of sex hormones.
What do barbiturates and insecticides induce?
induce/inhibit liver P-450
What do halogenated hydrocarbons disrupt?
biotransformation processes of sex hormones.
What do Halogenated hydrocarbons induce or inhibit?
LIVER P-450
What increases renal clearance?
When toxins disrupt biotransformation processes of sex hormones.
What is decreased at the FSH/LH receptor to granulosa cells when they are targets for chemical injury?
decrease receptor population.
What occurs to granulosa cells as targets for chemical injury in regards to the site of action of FSH and LH receptor?
competition for receptor
What are physical forces that influence the menstrual cycle?
light, noise, seasons, gravity
What are lifestyle factors that influence menstrual cycle?
Ethanol abuse, special diets, nutrition, illicit drugs, travel, stress, roommates, physical condition, tobacco use.
What are endogenous forces that influence the menstrual cycle?
age, body habitues: obesity, weight loss below ideal body weight.
What are pharmacological agents that influence the menstrual cycle?
with intrinsic estrogenic activity, causing hyperprolactinemia, affecting steroid metabolism, directly toxic to the ovary.
What are medical illness factors that influence the menstrual cycle?
endocrinopathies, autoimmune disorders, galactosemia, chronic renal failure, liver diseases, blood dyscrasias, and neurologic illness.
What are some radiation factors that influence menstrual cycle?
non-ionizing radiation and ionizing radiation.
What are other things that influence the menstrual cycle?
chemical toxicants and occupational exposure
