Reproduction Lectures (8) Flashcards
Why do humans consider themselves advanced over other animals?
Humans are sexually _____.
R1
- we mate for pleasure, not just procreation
- dimorphic: males and females have distinct characteristics determines by genome
Male and female sex organs (3 sets of structures)?
R1
gonads: gamete producing organs – testes VS ovaries
internal genitalia: accessory glands and ducts – epididymis, vas deferens, seminal vesicles, prostate VS fallopian tubes, uterus, cervix, upper vagina
external genitalia: external repro structures – penis, scrotum VS labia, clitorus, opening of vagina
Sex determination depends on _____. Why is the Y chromosome so small compared to X?
R1
fusion of egg (X always) with sperm and which sex chromosome the sperm contains (X or Y)
*Y has minimal genes on it, only carries male sex characteristics
Since the X chromosome has more genes on it compared to Y, is there a genetic imbalance b/n males and females?
R1
After development of ovaries in females, once X chrom is essentially “shut off” to balance with males
- only thing left on “shut off” X is pseudoautosomal regions at ends which would essentially match a Y chromosome
- whether paternal or maternal X is shut off differs in each cells: this is shown with cats of 2 colours
Why does X-linked recessive genetic disorders more commonly affect males?
R1
only need 1 X for it to show, compared to women who need 2 X’s to show it. *Females most often carriers
Abnormal sex chromosome distribution during Meiosis?
R1
by end of 2nd meiotic division, should end with 4 monosomic gametes. if not, have nondisjunction:
- 1st meiotic division ends with all going into 1 cell, by end of 2nd division, have 2 disomic gametes and 2 nullisomic gametes
- if nondisjunction only occurs at 2nd meiotic division, end with 2 normal monosomic gametes, 1 disomic gamete and 1 nullisomic gamete
Products of abnormal sex chromosome distribution during meiosis (syndrome’s)?
XXY, X, XXX, XYY, Y
R1
- XXY (Klinefelter’s): one disomic gamete fertilizes a normal monosomic gamete, extra X causes some female characteristics to form - tall stature, small testes, female-type pubic hair, osteoporosis, breast development sometimes, bad beard growth, infertile
- X (Turner’s): nullisomic gamete fertilizes a normal monosomic gamete, missing pseudoautosomal region of 2nd X - short, neck webbing, broad chest, widely spaced nipples, streak ovaries, infertile, amenorrhoea, pigmented nevi (moles)
- Y: non viable
- XXX: no real phenotypes, 2 X’s inactivated - correlated with learning disorders
- XYY: no real phenotypes, few genes on Y anyway so extra doesn’t affect much - correlated with learning disorders
After fertilization (union of egg and sperm) \_\_\_\_\_ forms. Then, \_\_\_\_ followed by \_\_\_\_. R1
Zygote. Then, blastocyst (3 weeks after fertil, followed by embryo, and eventually fetus (9 weeks after fertilization)
Difference between gestational and developmental timeline?
R1
Gestational starts from 1st day of last period (so it’ll be 2 weeks ahead of developmental) = 40wks
Developmental starts when fetus begins developing = 38wks (fertilization length)
Internal sex organ development in males and female embryos?
R1
Begins 7th week of development, before this embryo is bipotential
DEPENDS ON PRESENCE/ ABSENCE OF SRY GENE VIA Y CHROMOSOME: females are default essentially
Bipotential gonda: outer cortex and inner medulla
Accessory ducts: mullerian and wolffian
MALE: cortex regresses and medulla forms testis. Mullerian regresses (AMH present) and wolffian forms epididymis, vas deferens, seminal vesicles (testosterone present).
FEMALE: cortex forms ovary and medulla regresses. Mullerian becomes fallopian tube, uterus, cervix, upper 1/2 of vagina and wolffian regresses.
How does the SRY gene guide male internal genitalia?
R1
Sex determining Region of Y (SRY) chromosome produces testis determining factor (TDF; transcription factor) which guides development of gondal medulla into testis
-SRY gene takes up large portion of Y chrom
Testis then produce,
- anti-mullerian hormone (AMH or MIS; sertoli cells)
- testosterone (leydig cells): cause proliferation/growth of wolffian into male accessory structures
- testosterone converted to dihydrotestosterone (DHT; leydig cells) to cause external genitalia differentiation
External sex organ development in males and female embryos?
R1
after internal has developed
DRIVEN BY PRESENCE/ABSENCE OF ANDROGENS (DHT) MADE BY SRY GENE
bipotential genital tubercle, urethral groove, urethral fold, labioscrotal swelling
if female: genital tubercle forms clitorus, urethra folds and groove forms labia minora, opening of vagina and urethra, labioscrotal swellings form labia majora
if male: genital tubercle forms glans penis (head), urethra folds and groove forms lower portion of penis shaft, labioscrotal swellings form initial portion of shaft and scrotum
**at birth, testosterone causes descent of testes from abdominal cavity into scrotum.
What is the testis determining factor?
R2
Y chromosome SRY gene product - testosterone -> DHT is what converts medulla into testes
Dihydrotestosterone (DHT) importance came to light how?
R2
during studies of male pseudohermaphrodites who had a defective gene for 5a-reductase, the enzyme converting testosterone to DHT
- had testosterone, but no male external genitalia and prostate development since no DHT
- look female at birth (external genitalia does not develop)
- at puberty the testes secrete testosterone causing masculinization of external genitalia so male can chose which gender they want to be here
Male and female gametes?
R2
ovum: largest cell in body; non-motile so smooth muscle contraction and cilia move it; born with all oocytes will ever have, cyclically released during repro years (~40 years)
sperm: small; only flagellated cells in body; move far distance in female repro tract; continually produced for entire life once reached repro maturity; sperm and testosterone production diminish with age but don’t stop
Meiosis basic overview: 4 STEPS?
R2
1 - mitosis in utero to inc number of germ cells (oogonia or spermatogonia each with 46 chrom)
2 - DNA replicates but no cell division occurs, still 1 cell with 2 pairs of sister chromatids (homologous pair of replicated diploid chromosomes)= 92 chrom: 1º gamete
3 - first meiotic division, the one 1º gamete divides into 2 seperate 2º gametes (both diploid/sister chromatids, 46 chrom in each cell)
4 - 2nd meiotic division occurs, the 2º gametes both divide to end with 4 haploid daughter 3º gametes
*end with 4 viable gametes if male, in females only 1 will be viable (polar bodies)
Female gametogenesis?
R2
germ cells = oogonia
- mitosis (step 1) and the first stage of meiosis (step 2) occur during 5th month of fetal development so by birth, have all 1º oocytes (92 chrom) will ever have
- 5th month have 5-7 million oocytes
- meiosis resumes at puberty with cyclical recruitment of 1º oocytes to enter menstrual cycle
- 1st meiotic division (step 3) produces 1 large 2º oocyte (diploid) and tiny polar body
- ovary releases this diploid 2º oocyte and will not undergo the division unless fertilized
- 2º oocyte begins 2nd meiotic division (step 4) and polar body breaks down during ovulation
- if not fertilized, is released out of body. If fertilized, undergoes the division (step 4) to yield 1 haploid gamete and a polar body
What are polar bodies and why are they non viable?
R2
uneven division in cytokinesis yield polar bodies with very little cytoplasm and few organelles, unable to thrive
- uneven distribution comes from the female gamete needing all necessary cytoplasm/proteins/organelles/energy for the zygote as sperm only supplies some DNA
Both male and female gametogenesis is under control of _____.
R2
hormones from brain (signalling cascade) and endocrine cells in gonads
Male gametogenesis?
R2
- small amnt of meiosis occurs in fetal development to inc immature germ cell numbers (spermatogonia) in testes
- at puberty: germ cell mitosis (step 1) resumes
- some spermatogonia will remain as immature germ cells and continually make more sperm (stay in mitosis step)
- some spermatogonia are recruited to enter cycle to produce 1º spermatocytes (step 2)
- 1º spermatocytes undergo 1st meiotic division to produce two 2º spermatocytes (step 3)
- both 2º spermatocytes undergo 2nd meiotic division to produce 4 immature spermatids (step 4)
All 4 viable
How does the brain direct reproduction?
R2
- peptide hormones from hypothalamus go to anterior pituitary, cause secretion of hormones which go to gonads to cause secretion of sex hormones: androgens (DHT, testosterone), estrogens (estradiol - from testosterone), progesterone (progestin)
- males make primarily androgens: 95% made in testes and 5% in adrenal cortex. Most testosterone is converted to DHT in peripheral tissues - both agonists for androgen receptors but DHT is more potent
- females make primarily estrogens and progesterone: most made in ovaries. Some testosterone made in adrenal cortex
Hypothalamic-pituitary gonadal axis (HPG axis)?
R2
control pathway for sex hormones
- gonadotropin releasing hormone (GnRH) released pulsatile-ly in hypothalamus travels to anterior pituitary
- produced either in GnRH or kisspeptin neurons
- cause secretions of 2 anterior pituitary gonadotropins from gonadotropes: follicle stimulating hormone (FSH) and luteinizing hormone (LH)
- FSH and LH act on gonads to stimulate sex hormone production and influence gamete production
Precursor for all peptide hormones?
R2
Cholesterol
Hypophyseal portal system describes _____. Explain the process.
R2
- describes how hypothalamic hormones reach anterior pituitary
- GnRH neurons release GnRH into capillaries of portal system
- portal veins carry trophic neurohormone to anterior pituitary where they act on endocrine cells
- endocrine cells release their hormones into 2nd set of capillaries for distribution to rest of body
Feedback pathways that influence GnRH (and ultimately FSH and LH) release during gametogenesis? What are inhibins and activins?
R2
neg feedback: LH and FSH inhibit GnRH release
- in males high amnts of androgens, prog., estrogens -ve feedback loop to dec GnRH release
- in females its same but with high amnts of estrogen, +ve feedback to inc GnRH
Inhibin: peptide hormone that inhibits FSH producing gonadotropes
Activin: opposite
Why is positive feedback loop of estrogen and GnRH needed?
R2
significant role in female repro cycle since more estrogen drives egg release
Feedback loop: responses for testosterone, estrogen and progesterone specifically?
R2
testosterone: neg feedback to kisspeptin and GnRH (hypothalamus), and gonadotrope neurons (anterior pituitary)
estrogen/progesterone: neg feedback on gonadotrope neurons (to dec LH and FSH) always, neg or POS feedback on kisspeptin neurons only! GnRH neurons do not have estrogen receptors
GnRH release specifics? What happens with GnRH deficiencies?
R2
- pulsatie-ly released from hypothalamus every 1-3 hours in both sexes, until there is a feedback
- low levels of androgens and estrogen = pulsatile release so pulsatile production of LH and FSH and sex hormones
- inhibition starts once levels high unless estrogen is high enough in females to result in ovulation
- in kids with a deficiency, they will not sexually mature since no sex hormone production
- need gonadotropin stimulation in gonads: synthetic GnRH delivered pulatile-ly
Why does synthetic GnRH have to be delivered in pulsatile manner?
R2
- constant delivery causes down regulation of receptors in pituitary (resistance)
- gonadotropes stops LH and FSH production
- prevents sexual maturity
Pulsatile release of GnRH is regulated by?
R3
hormones (neg feedback loop), stress, circadian rhythm, environmental stimuli
Environmental factors influencing reproduction?
R3
best studied in females since monthly cycle showing repro cycle is (ab)normal
- affected by: nutritional status, amnt of physical activity, change of day/light cycles altering circadian rhythm
- “environmental estrogens” can bind and activate estrogen receptors/interfere with binding site (anti-estrogens) e.g. phytoestrogens (soy products, pesticides, toxins, fish since synthetic hormones released into water..)
can influence a developing fetus and affect aggressiveness/docile-ness (not proven in humans yet)
Male reproductive structures within/on penis?
R3
urethra: urethra and semen passageway
corpus spongiosum: erectile tissue that surrounds urethra to hold it open during erection (inc blood flow) (protective function)
corpora cavernosa: 2 columns of erectile tissue that cause erection when they fill with blood
prepuce: foreskin; can be removed for hygiene etc.
-some evidence that removing it reduces transmission of HIV and STIs and prevalence of cancer and UTIs
Male external genitalia?
R3
penis
scrotum: external sac testes migrate into for sperm production since it needs colder temp
if testes do not migrate into scrotum during 1st year, can become infertile; if not descending, given artificial testosterone to induce movement or are surgically moved
Male internal genitalia?
R3
accessory glands: seminal vesicle, prostate, bulbourethral glands = produce secretions making up liquid in semen
vas deferens - tube connecting testes to urethra, empty secretions from accessory glands into urethra to join with sperm
Prostate gland?
R3
- most common cancer of men is prostate cancer since its a tissue that grows continuously throughout life so its prone to DNA errors
- urination problems and cancer risk if hypertrophy of prostate tissue
- DHT involved in prostate development so administration of 5a-reductase inhibitor (finasteride) will block/reduce DHT production to shrink prostate tissue
- finasteride can also be taken for balding since DHT shrinks hair follicles
Testes are made up of (structures)?
R3
- male gonad: produces sperm and hormones
- pair of ovoid structures ~2.5cm by 5cm
- 1 teste = tough fibrous capsule of 250-300 compartments
- within 1 compartment = coils of 400-600 seminiferous tubules (site of sperm production), blood vessels and leydig cells (lie b/n tubules)
- tubule feeds into epididymis (site of sperm storage and maturation)
- epididymis feeds into vas deferens
Seminiferous tubules?
R3
site of SPERM PRODUCTION
- developing spermatocytes stack in columns from outer edge -> lumen
- sertoli cells (main controller of spermatogenesis) in between each column
- outer edge spermatocytes are called spermatogonia, as they proceed inward, become sperm
- outer edge (interstitial space outside tubules) is lined with capillaries and leydig cells: produce testosterone
surrounding the tubule are Myoid cells: epithelial cells that secrete basal lamina layer to keep out large particles but allows testosterone to still enter tubules. i.e. controls internal environment
Sertoli Cells?
R3
spermatogonia contain tight junctions with adjacent sertoli cells (and basal lamina) to form a blood-testis barrier b/n tubule lumen and interstitial space to control what enters lumen of tubule, and internal enviro
- so sertoli cells regulate sperm development
- “sustentacular cells” = provide sustenance/nourishment to developing spermatocytes
- produce hormones, growth factors, enzymes for mitosis/meiosis, androgen binding protein which binds testosterone to keep it in the lumen
General development of sperm inside a seminiferous tubule?
R3
germ cells resting just inside basal lamina: some stay here to continue mitosis, some move forward as they differentiate in meiosis.
- as more sperm enter meiosis essentially push previous sperm forward into lumen
- sertoli cells tight junctions break and reform around migrating cells
- once reaching the lumen, one spermatogonia will undergo 1st and 2nd meiotic divisions to produce 4 immature spermatids
- spermatids remain embedded in apical membrane while they complete maturation
Sperm maturation on apical membrane of seminiferous tubules?
R3
- chromatin/nucleus condenses
- microtubule extension (base of nucleus extends outwards to become flagella)
- acrosome (cap over nucleus) forms, contains enzymes needed for fertilization
- mid-piece (body) is full of mitochondria for ATP (flagella)
this process (spermatogonium -> free mature sperm) takes ~64 days
at this point, unable to swim
How do the un-motile mature sperm leave the seminiferous tubules?
R3
pushed out of tubule lumen by other developing sperm and bulk flow of fluids into epididymis
- mature (become motile) in epididymis for ~12 days and hang out here until ejaculation occurs epididymal cells secrete proteins allowing complete maturation
Spermatogenesis requires ______ and ______.
R3
gonadotropins (LH and FSH) and testosterone
- FSH binds sertoli cells, they generate paracrines needed for mitosis and meiosis
- FSH secretes ABP needed for bringing testosterone into tubules
- FSH causes sertoli cells to release inhibin, inhibits FSH
- LH targets interstitial leydig cells, they make testosterone, which is an inhibitor of LH and GnRH neurons
Inhibition of FSH and LH is mainly through _____.
R3
Inhibin: only FSH
testosterone: only LH, and GnRH neurons in hypothalamus
Male accessory glands? What are the secretions made of?
R3
- sperm leaving vas deferens is joined by accessory glands secretions creating semen (99% of semen is secretions)
Secretions: nutrients for sperm, buffers (acidic enviro of vagina, residual acidic urine in urethra), chemicals to inc motility, prostaglandins for motility and contraction, protective secretions e.g. immunoglobulins, lysosomes
___ influence primary and secondary sex characteristics. What are the primary and secondary sex characteristics?
R4
androgens – anabolic hormones; receptors are nuclear receptors i.e. act on DNA to promote transcription
primary: internal sex organs, external genitalia
secondary: body shape, facial/body hair growth, muscular development, thickening of vocal cords (voice lowering), behavioural effects (libido, aggression)
Why do steroids (which are androgens) increase muscle growth?
R4
receptors are nuclear receptors so they act on DNA to promote transcription which is important in skeletal muscle growth
also works everywhere tho: brain, heart, liver, skin, bones, kidneys
Female external reproductive structures?
R4
collectively referred to as vulva
labium majus/majora: similar tissue to scrotum
**labia minora and major protect the other external structures
clitorus: bud of erectile and sensory tissue. “clitoral hood” overtop
urethra: urine
opening of vagina: penis receptacle
hymen: layer of skin outside vagnia partially covering the opening
Vagina leads to ____. What is the function of this structure? Anatomy of it’s wall (3 layers)?
R4
cervix (opening of uterus) -> uterus (womb)
uterus is where fertilized egg implants and develops
thin “outer” connective tissue layer = perimetrium
thick middle layer of smooth muscle= myometrium
“inner” glandular layer of epithelial cells = endometrium where blastocyst embeds, what is shed during menstruation, and is needed for expelling a fetus
Process of egg and sperm making it to each other/fertilizing? cilia
R4
sperm swim into vagina -> cervix -> uterus -> fallopian tubes to meet egg right outside the ovary
egg is released into fallopian tubes which have 2 layers of smooth muscle, the inner layer of which is lined with cilia. Cilia beats and moves egg from ovary -> fallopian tube where it is fertilized.
Cilia beat to move fertilized egg to uterus for implantation, or expulsion if unfertilized
Why are cilia so important in the fallopian tubes?
R4
End up with ectopic pregnancy if no cilia to move fertilized egg into uterus, since sperm meets egg right outside ocary
What are fimbriae?
R4
“fingers” of fallopian tubes that drape over top the ovary and move slightly to help/ensure the ovulated egg is drawn into fallopian tube
Female Gonad: Job and structures?
R4
Ovaries/follicles: make eggs/hormones
- bit smaller than testes
- thick outer cortex of connective tissue surrounds ovary: site of oocyte production
- inner connective tissue layer (stroma): small central medulla w vasculature, holds everything together
Follicle development (i.e. how menstrual cycle starts)? R4
- birth: 500 000 primordial follicles (1º oocytes with pre-granulosa cells layer surrounding) (step 1)
- puberty: 180 000 primordial follicles **only ~480 released in 40yrs
- cyclical recruitment of primordial cells ~1 year before menstrual cycle starts
- 100s recruited into 1º follicles (more granulosa cells) cuboidal shape (step 2)
- these 1º follicles undergo 1st meiosis into 2º follicles with many layers of granulosa cells, and THECA cell in stroma (step 3)
- 2º follicles develop ANTRUM (fluid filled cavity w enzymes/hormones) = 3º follicles
- ~20 3º enter menstrual cycle, only 1 fully develops (step 4)
Growth of primordial -> primary -> secondary -> tertiary follicle is _______ of HPG axis.
R4
Independent
- local cell signalling sub’ made within ovary recruit primordial follicles and develop them over a year period into tertiary.
- once tertiary, then depend on HPG axis (FSH mainly)
Ovarian cycle (menstrual cycle)? R4
*start of period = day 1
– follicular phase (~first 2 weeks): recruitment and growth of ~20 tertiary follicles under FSH direction. By day 7, 19 undergo atresia, end with 1 dominant follicle.
– ovulation (day 14): 16-24h before ovulation, meiosis occurs as LH surges, becomes 2ndary. 2ndary oocyte is released from tertiary follicle into fallopian tubes
– luteal phase: (~last 2 weeks): left behind granulosa and theca cells become luteal (yellow; fat) cells so the ruptured follicle/ovary (no oocyte in it anymore) becomes corpus luteum which produces hormones to maintain endometrium in uterus in case fertilization occurs.
*corpus luteum works for ~10 days, then degenerates if egg is not fertilized and menstruation begins again
Uterine (menstrual cycle)?
R4
*start of period = day 1
– menses: (3-7 days) degeneration of corpus luteum, shedding of endometrium and some blood
– proliferative phase: (~7 days): uterus adds new cells to endometrium in anticipation of pregnancy.
– secretory phase: (~14 days): after ovulation, hormones (progesterone) from corpus luteum convert endometrium into thickened secretory structure for blastocyst to survive.
*If unfertilized, superficial endometrium layers are lost during menstruation, cycle restarts.
Hormonal control of menstrual cycle (ovarian and uterine)?
R4
menses/start of follicular (day 1-7): high GnRH release (repressed for rest of cycle after this) stimulates FSH and LH release
- estrogen, progesterone, inhibin (inhibits FSH) and anti-mullerian hormone start to be released from ovary
during end of follicular/entire proliferative phase (day 7-14) estrogen is primary controller (inhibit GnRH)
ovulation occurs ~day 14 as estrogen switches to + feedback on GnRH: LH (and FSH) surges *FSH is still inhibited by inhibin
during luteal/secretory phase (day 15-28), progesterone is primary controller some estrogen and inhibin tho
Hormones during early to mid follicular phase (week 1)?
R4
during period
- pulsatile GnRH secretion since corpus luteum hormones no longer repress it
- FSH recruits ~20 tertiary follicles for maturation
- LH stimulates theca cells to secrete androgens (androstenedione)
- FSH stimulates granulosa cells to convert androgens to estrogen and secrete AMH to prevent more follicular recruitment
- when estrogen gets high, -ve feedback to anterior pituitary and hypothalamus (less GnRH and LH/FSH), +ve on granulosa cells to inc estrogen
- estrogen begins proliferation of endometrium
Hormones during late follicular phase to ovulation?
R4
estrogen peaks
– some follicles undergo atresia, dominant follicle persists
– granulosa cells release progesterone and inhibin
– persistently high estrogen for 1-2 days reverses feedback to become +ve on hypothalamus
– inc GnRH, LH surges more than FSH (inhibin)
– high estrogen readies endometrium and high LH drives ovulation
Ovulation process
R4
16-24 H after LH surge
– LH causes 1º oocyte maturation: meiosis resumes, 1st division occurs to 2º oocyte
– mature follicles secrete proteolytic enzymes to breakdown its collagen and connective tissue and release oocyte, as well as secrete prostaglandins to allow oocyte to exit ovary and be swept by fimbriae
Hormones during early to mid luteal phase?
R5
– thecal and granular cells transform into luteal cells in atrum, under direction of LH surge
– lipid droplets and glycogen granules accumulate in cytoplasm (yellow colour), and begin to secrete progesterone
– progesterone (and estrogen) levels steadily rise, -ve feedback to hypothalamus and anterior pituitary
– progesterone causes endometrium to become secretory structure in prep for blastocyst, and thickens secretions from cervix (cervical plug preventing bacteria and more sperm)
Hormones during late luteal phase?
R5
– corpus luteum (luteal cells) keep producing progesterone and estrogen for 12 days post ovulation
– if fertilized, blastocyst releases HcG to maintain it until placenta forms
– if unfertilized, spontaneous apoptosis of corpus luteum to corpus albicans (white, macrophages digest it) takes 2 days
– progesterone/estrogen drop, GnRH inc, FSH/LH inc
– endometrium sheds as progesterone dec (vessels contract backwards, less O2 and nutrients)
– 14 days post ovulation, menstruation begins
– menstruation is ~40ml blood, 35ml serous fluid and cell debris. ~3-7 days
Hormones involved in female secondary sex characteristic formation?
R5
– estrogen: breast development, fat distribution to hips and upper thighs (hips)
– androgens (LH and FSH): pubic and armpit hair, libido
Requirements for union of sperm and egg in humans?
R5
– females must have receptacle for sperm to enter
– males but have organ to deposit sperm in receptacle
– cannot occur when resting, male is flaccid (can’t be inserted into vagina), requires penis to stiffen/enlarge (erection)
Human sexual response steps? (4)
R5
– 1. excitement: erotic stimuli prepare for copulation ex, in bp, heart rate, respiratory rate
– 2. plateau: changes that started during excitement phase intensify (more blood flow to the penis/clitorus/vagina wall/labia minora, inc heart rate, bp, respiratory rate)
– 3. orgasm: both sexes, series of skeletal muscle contractions (uterus, vagina) accompanied by intense pleasure and continued inc bp, heart rate and respiratory rate
– 4. resolution: parameters return to normal
Erection in both sexes is a state of ________. (excitement phase) What are some erotic stimuli?
R5
Vasocongestion (inc arterial blood flow) into spongy erectile tissue which exceeds venous outflow
males: capris spongiosum and corpora cavernosa
females: labia minora, vagina walls, clitorus
stimuli: tactile, sensory, physiological stimuli .. to erogenous zones (sexually stimulated areas)
Erection reflex in men?
R5
– erotic stimuli inhibits sympathetic pathway, stimulates parasympathetic input, causing erection via Nitric oxide:
– parasympathetic neurons stimulated and ACh released binds muscarinic ACh receptors on endothelial cells, resulting in NO production, which enters vascular smooth muscle cells, causes relaxation (activates myosin light chain phosphatase)
– 2 cavernosal columns in penis have arteries in the centre which dilate from NO (inc inflow into spongy tissue): amnt of blood coming into arteries exceeds amnt of blood leaving in veins, engorging penis and compressing superficial (outside) veins
Movement of semen out of the male body (2 processes).
R5
1 – emission: sympathetic activation of smooth muscle and accessory glands; waves of contraction move sperm out of epididymis, through vas deferens, into urethra where its joined by secretions to make semen
2 – ejaculation: somatic/skeletal muscle contractions; expulsion of ~3ml of semen from urethra out of body via series of rapid muscular contractions in base of penis, accompanied by pleasure.
**these can happen in absence of mechanical stimulation: non-sexual erection during REM sleep
Sexual dysfunction? Main cause in men?
R5
inability to achieve/sustain erection, disrupts sex act for both men and women not infertility
in men: erectile dysfunction (diabetes, early warning sign of cardiovasc disease/atherosclerosis, neurological disorders like MS and parkinson’s symptom is ED, stress and anxiety, some drugs all dec NO production)
Erectile Dysfunction treatments?
R5
PDE5 inhibitors inhibit the enzyme (phosphodiesterase 5) that converts cGMP back to GMP, thus reducing vascular smooth muscle relaxation
these inhibitors allow for continual cGMP conversion so myosin light chain is activated and more Ca+2 is reuptake-d into SR
Female sexual dysfunction is most commonly ______. Treatments?
R5
low sexual desire
– flibanserin helps restore prefrontal cortex control over brains motivation/reward pathways enabling sexual desire: activate serotonin receptors to inc dopamine/norepinephrine during sex to inc reward pathway from sexual desire
_____ therapy is sometimes prescribed for postmenopausal women with low sexual desire.
R5
Androgen therapy: drug in trial is Bremelanotide – acts on melanocortin receptor in hypothalamus believed to be involved in upregulating women’s sexual response to appropriate cues
- injected
- more effective vs flibanserin
- first invented by self-tanner in pill form
Contraceptives are designed to _____. 3 types of contraceptives?
R5
prevent pregnancy
- 85% of women having regular unprotected sex get pregnant within a year
: abstinence (or cyclical abstinence), sterilization (most effective), interventional methods (barriers, implantation prevention, hormones)
Contraceptives: sterilization method for both men and women?
R5
best to be saved for after had kids since not easily reversible
tubule ligation in women: prevent union of egg and sperm by cutting and tying/cauterizing/banding fallopian tubes
vasectomy in males: cuts vas deferens to prevent travel of sperm to penis
Contraceptives: Barrier methods? (5)
R5
*ancient egyptians used vaginal plugs to prevent pregnancy!
–diaphragm: silicone cup covering cervix/wall of vagina
–cervical cup: smaller than diaphragm, fits over cervix head
*diaphragm and cervical cup usually have spermicide added to them manually
–sponge: diaphragm but already w spermicide
–condom
–female condom: lines entire vaginal wall and covers cervix
Contraceptives: implantation prevention methods? Side effects?
R5
IUD (most successful contraceptive if not sterile): plastic devices that create mild inflammatory reaction in endometrium to prevent implantation of blastocyst, as well as kill sperm
- left in uterus against the walls for 5-12 years
- some wrapped in copper (spermicide)
- some secrete progesterone slowly to inc production of thickened mucus at cervix and reduce endometrial proliferation (dec/stop menstruation)
side effects: pain and bleeding to infertility caused by pelvic inflammatory disease and blockage of fallopian tubes
Contraceptives: hormonal treatments basics e.g. goal, history? Types? (5)
R6
- females only
- goal: interrupt HPG axis to dec oogenesis or ovulation
- history: girls take plant concoctions phytoestrogens
: depo injection (every 3mo, progesterone, prevents ovulation)
: vaginal ring (replace every month, releases progesterone/estrogen)
: arm implant
: transdermal patch
: pill (1960s *various combos of estrogen/progesterone to alter hypothalamus/a. pituitary, dec GnRH, inhibit gonadotropin release for ovulation, thicken cervical mucus *depends on brand)
Male hormonal contraceptives??
R6
RISUG/VaslGel: vasectomy w/o damaging vas deferens; polymer gel injection into vas deferens to coat the walls and kill passing sperm; reversible with bicarbonate injection; in phase 3 clinical trials, many unanswered q’s
NES-T: gel; rub on back of arms; contains progestins to supress HPG axis to suppress testosterone and sperm production; added testosterone in gel; initial results show complete suppression of spermatogen. in 90% of men; reversible
Vaccines attempted; produce antibodies to sperm
Currently, only male contraceptive is condom
Infertility is the inability to ____. Most common cause?
R6
inability to conceive
– *low sperm count: normal is 200 million/ejaculation and only half make it to fallopian tubes; anything under 39 million is low. Usually low testosterone is cause, can be STIs (chlamydia, gonorrhea), prostatitis (prostate inflammation prevent sperm movement into urethra), mumps (testes inflammation)
*can also be abnormal shape (structure) or abnormal motility
Another major cause of infertility in men? Minor cause in males and females?
R6
major: varicocele – varicose veins w/n testes; defective valves w/n veins cause pooling of blood and inc in temp which dec sperm number
minor: females or males produce sperm antibodies
another minor: retrograde ejaculation – inner urethral sphincter doesn’t contract, semen doesn’t leave body right, goes into bladder
5 types of infertility in women?
R6
– damaged fallopian tubes (STIs, surgery, pelvic tuberculosis) have scar tissue; prevent movement of fertilized egg down or sperm up
– endometriosis: endometrial proliferation outside uterus (can’t exit body) causes scar tissue by ovaries/tubes
– PCOS: higher androgen levels cause frozen follicles on ovaries; can be hypothalamic dysfunction, premature ovarian insufficiency (small primordial follicle pool)
– uterine/cervical disorders: endometrial polyps, fibroid formation around tube entrance so fert. eggs can’t go down
– cervical stenosis: narrowing of cervix after trauma/pelvic surgery
Assisted reproductive technology: in vitro fertilization stats? Process?
R6
1st baby born in 70s! av of 31% success first try, varies with age ... ≤ 35 = 41-43% ≥ 40 = 13-18% ≥ 45 = ~5%
- female given hormones to stimulate egg production (inc # of 3º dominant follicles)
- many eggs vacuumed out from ovaries
- eggs mixed with mans sperm cells in culture dish to fertilize
- blastocysts put in incubator for 48h
- embryos implanted in females uterus or frozen
Assisted reproductive technology: artificial insemination?
R6
- inc # of sperm making it up to tubes
- where sperm is deposited differs …
•intracervical (ICI)- cheapest, least invasive
•intratubular (ITI)- most effective
•intrauterine (IUI)
Fertilization requires… step 1: capacitation?
R6
- sperm sheds surface glycoproteins, sterols, CHOs in the cervix/uterus allowing them to swim fast (inc Ca+2 permeability), as well as expose receptors needed to penetrate egg
- response to female substances: albumin, lipoproteins, proteolytic enzymes
- during in vitro, before sperm injected into eggs, they are rinsed to cause this
- egg may produce chemical attractants to aid in fertilization 6-24h after ovulation (why it happens so close to ovary distal region)
Fertilization requires… step 2: acrosomal reaction?
R6
1º oocyte ovulates, becomes 2º oocyte. Enters tubes with some granulosa cells attached forming corona radiata layer. Sperm must penetrate it and the inside glycoprotein layer (zona pellucida). The acrosome (head) of sperm releases enzymes needed to dissolve cell junctions b/n granulosa cells allowing sperm to squeeze through and breakdown a section of zona pellucida
Fertilization requires… step 3: cortical reaction?
R6
after sperm binds receptors on egg (why capacitation is needed), plasma memb’s fuse, initiating cortical.
- prevents polyspermy: makes zona pellucida impenetrable – cortica granules w/n egg exocytose proteolytic enzymes that harden zona
- Then nucleus of sperm is donated, 2nd meiotic division occurs forming 2nd polar body (expelled) and haploid egg. DNA fuses to form diploid zygote
Timeline of fertilized zygote–> blastocyst? How does gestational vs developmental dating work?
R7
zygote has 6 days of cell divisions as it proceeds from the fallopian tubes into the uterus, via smooth muscle contractions and cilia in tubes (progesterone directed)
-a week after fertilization occurs, the now blastocyst implants into endometrium
since gestational dating starts on 1st day of last menstrual cycle, by the time fertilization /ovulation occurs, considered 2 weeks pregnant, 0 days developed. When implantation occurs, 3 weeks pregnant, 1 week developed
Blastocyst basics?
R7
- 100 cells implanting into uterine wall
- TROPHOBLAST: outer cell layer that surrounds inner cell mass layer, and is what invades the endometrium wall 7 days post ovulation.
- Upon contact w endometrium trophoblasts proliferate and secrete proteolytic enzymes allowing blastocyst to penetrate/bury into wall and throughout development, embryo is completely surrounded by endometrium
Trophoblast of blastocyst forms ______. What does the inner cell mass form?
R7
-CHORION = extraembryonic memb enclosing embryo and forming placenta
- forms EMBRYO and other extraembryonic membs:
- AMNION (secretes amniotic fluid existing w/n chorion as a protective cushion for embryo; assists in developing skeletal muscles since embryo can move/float)
- ALLANTOIS (umbilical cord)
- YOLK SACK (serves as circulatory system, absorbs nutrients/subs from amniotic fluid that diffuse into embryo; disappears once placenta forms)
How does the placenta form?
R7
- a section of chorion starts to form chorionic villi that penetrate vascularized endometrium that formed in secretory phase of uterine cycle
- chorionic villi have vasculature from embryo
- chorionic villi secrete enzymes that breakdown endometrial walls and maternal blood vessels to allow moms blood to empty into intervillous space and bathe chorionic villi so the embryo gets O2 blood
Is there a direct connection b/n mother’s blood and embryo’s blood?
R7
NO
- intervillous space is where nutrients, gases, wastes get exchanged across membs of villi (diffusion)
- umbilical cord has 1 vein bringing O2 nutrient-filled blood into embryo, and 2 arteries carrying deO2 waste-filled blood away from embryo
- placenta grows to 20 cm in diameter and can receive up to 10% of maternal CO – diameter allows more maternal blood to bathe the villi allowing more exchange
Human chorionic gonadotropin hormone role?
R7
embedded blastocyst immediately begins secreting hCG to keep corpus luteum intact, since it is needed to maintain endometrium layer
- hCG is similar to LH so it binds to LH receptors in corpus luteum and keeps its hormone secretion going
- hCG initially stimulates testosterone/DHT production in developing testes in male fetuses after 7 weeks
- hCG is hormone detected in pregnancy test since it only starts after blastocysts embeds (3 weeks after menstruation)
- after 7 weeks of DEVELOPMENT placenta is formed and takes over estrogen/progesterone levels, corpus luteum can degenerate
When does hCG levels drop during pregnancy?
R7
after placenta takes over since corpus luteum does not need to be maintained
Which hormones does the placenta secrete?
R7
- Progesterone/Estrogen: neg feedback to HPG axis prevents follicle development and initiation of another menstrual cycle.
- Estrogen inc # and size of milk secreting ducts in breasts.
- Progesterone maintains endometrium, suppresses smooth muscle contractions to prevent premee uterine contractions
- Human placental lactogen (hPL; human chorionic somato-mammotropin, hCS) is similar to growth hormone and prolactin, alters mother’s glucose and fa metabolism to support fetal growth (dec insulin sensitivity so more glucose uptake into tissues/blood, inc lipolysis so more fa in blood, this ensures more energy available for embryo
- *not for breast development and milk production**
Why do 4% of pregnant women have gestational diabetes?
R7
insulin insensitivity due to human placental lactogen (hPL) i.e. human chorionic somatomammotropin (hCS)
Parturition process begins with ____. What are the 3 possible initiators of the sudden labour?
R7
birth occurs b/n 38-40th week of gestation
-labor: sudden rhythmic contractions of the uterus myometrium layer
- progesterone and estrogen drop: in some animals, not in humans (doesn’t drop until placenta is removed)
- oxytocin inc: but doesn’t inc in humans until after labour begins used to induce labor
- placenta releases corticotropin releasing hormone: some evidence high enough CRH can cause premee labor
Days before labor the ____ softens and ____ loosen. These two events are under ____ control. What is the positive feedback loop in birth?
R7
cervix softens so baby can pass through; ligaments holding pelvic bones together loosen so pelvis can open wider.
These 2 are under enzymatic control: high estrogen/relaxin from placenta
initiation of contractions, fetus pushed lower, pressure on cervix, cervix stretched, sensed by stretch receptor, sends info to MNC receptors in hypothalamus, releases oxytocin, causes more uterine contractions top-bottom and prostaglandin and CRH release, inc force of contractions, baby pushed down ….. contractions gets more forceful and frequent as it continues
The structure of a breast mammary gland?
R7
similar to sweat glands
- each gland has 15-20 lobes surrounding nipple
- each lobe has many lobules
- each lobule has many acini/alveoli
- acini surrounded by epithelial milk secreting cells and myoepithelial cells
- smooth muscle lines duct walls
- milk production occurs in acini, ejected into lobular glands and feeds into larger milk ducts to exit breast
- milk contains lots of fats and protein
Lactation process?
R7
*puberty: estrogen= milk duct proliferation, fat deposition
pregnancy:
- milk glands develop more w inc estrogen, growth hormone, cortisol, and progesterone converts epithelial cells into secretory structures later on
- high estrogen/progesterone inhibits milk production so milk doesn’t come in until placenta is removed: initially colostrum is made (inc protein, antibodies, immuno’s)
3 days after birth:
- prolactin inc 10fold from anterior pituitary (bc est/prog drops and prolactin inhibitory hormone drops later in pregnancy): stimulates acini cells
- oxytocin causes milk ejection: mechanical activation of sensory neurons in nipples stimulates hypothalamic oxytocin, causes smooth muscle contractions in breast (myoepithelial) and uterus
- can occur w/o pregnancy if higher brain centre is activated e.g. hearing a baby cry
Puberty growth?
R7
- quickly in females: breasts bud and period starts, av of 12 years old (range 8-13)
- subtle/slow process in men: growth/maturation of genitalia, pubic and facial hair, voice lowering, inc in testosterone so height etc. 9-14 years old
maturation of HPG axis occurs: inc in pulsatile GnRH release
- genetically pre-programmed: inheritance patterns w mom/daughter timing of first menstrual cycle
- low adipose tissue in females (leptin) can cause women to miss periods e.g. intense athletes
Aging in females (i.e. stopping of period)?
R7
Menopause: ~40yrs after 1st menstrual cycle; ovaries no longer respond to LH/FSH since no more follicles to recruit; absence of estrogen causes hot flashes, osteoporosis etc; must not have had a period for 1 year. Perimenopause is the time leading up to it with infrequent periods.
Menopause but in men is _____.
R7
“andropause” - not real
-testosterone dec with age causing less sperm production, energy, lean muscle mass, ability to hold an erection; dec in testosterone due to dec # of leydig cells and responsivity to LH (could be dec HPG axis activity)
