Human Reproductive System Flashcards
What are the important endocrine glands in the human reproductive system?
- Hypothalamus
- Pituitary (Anterior and posterior)
- Gonads
What is the function of the gonads in the reproductive system?
Produce gametes and reproductive hormones
What are the water soluble hormones important in the reproductive system?
Peptides and proteins, including:
- GnRH
- FSH
- LH
- Oxytocin
Where is GnRH produced?
Hypothalamus
Where does GnRH act?
The anterior pituitary and the gonads
Where are FSH and LH produced, and what releases them?
The anterior pituitary, where they are released by GnRH
Where is oxytocin produced?
The posterior Pituitary
What are the lipid soluble hormones involved in the reproductive system?
Androgens
Oestrogens
Progestagens
Where are androgens produced?
Testes
Where are oestrogens and progestagens produced?
The ovary
What are the principal androgens, and how do they differ?
Testosterone
5- alpha dihydrotestosterone
Both are made from cholesterols, although they have different side-groups
5 alpha is much stronger than regular testosterone
What are the principal oestrogens and what are they for?
Oestradiol- main oestrogen
Oestrone- weaker, more important for menopause
Oestriol- softens the cervix for childbirth
What hormones released from the hypothalamus are responsible for reproduction, and how are they regulated?
There is only one hormone- GnRH. There is no equivalent inhibiting hormone.
It relies on negative feedback for regulation (apart from ovulation, which uses positive feedback).
How are reproductive hormones released from the hypothalamus?
They are pulsatile- a burst is released every 1-2 hours.
Why is it beneficial that GnRH travels from the hypothalamus to the ant. pituitary via a specific portal system?
It means that the hormones are not lost in general blood circulation.
Why is it important to have a hypothalamus- ant. pituitary - gonadal axis?
It allows the signals to be amplified.
What are the 5 different classes of hormone produced by the hypothalamus?
Somatotrophs Thyrotrophs Lactotrophs Corticotrophs Gonadotrophs
How does the posterior pituitary function, what hormones is it responsible for and what are their functions?
Secretory hormones are synthesized in the hypothalamus, travelling bound to carrier proteins down the axon and into the posterior pituitary, to terminals where they are stored in secretory vesicles.
When an AP arrives, they are released into the bloodstream.
Hormones are oxytocin and ADH.
ADH retains water, while oxytocin affects smooth muscle contraction, causing milk ejection and uterine contractions. It also has a role in pair bonding.
How does the anterior pituitary function, and what does it release?
The hypothalamus produces inhibiting and releasing hormones, and nerve impulses causes their release into the primary plexus and down to the anterior pituitary. These act on specific secretory cels, which secrete their products into the efferent veins.
What is the hypophyseal portal system?
A vascular arrangement in which blood flows from one capillary bed to another without going through the heart. It prevents signal dilution.
What is pulsatile release?
Secretions are released in discrete bursts, and separated by periods of little or no secretion
Why is pulsatile release important?
It prevents desensitization and down-regulation of receptors.
What are the hormones regulating gonadal activity?
FSH and LH
What do FSH and LH do in the female?
FSH: Promotes growth/development of ovarian follicles
LH: Secretion of female sex hormones and the trigger for ovulation
What do FSH and LH do in the male?
FSH: Growth of spermatozoon
LH: Production of testosterone
What is testosterone?
An androgen, the main secretory product of the testis, associated with development and maintenance of male characteristics and fertility.
What does testosterone do?
Male sex development Spermatogenesis Sexual behaviour Muscle development - However, excessive amounts reduce fertility
What are oestrogens?
Main role is the development and maintenance of the female characteristics and fertility
Mainly produced by granulosa cells of growing follicules
What do oestrogens do?
Female sex development
Growth of endometrium
Regulation of menstrual cycle
Bone growth (poor bone growth and osteoporosis is a sign of an oestrogen deficiency)
What are progestagens?
Major steroidal hormones of corpus luteum and placenta.
Associated with prep and maintenance of pregnancy.
What is the vagina?
An elastic muscular tube, extending from the cervix to the exterior of the body, having 3 main functions:
- Passageway for elimination of menstrual fluids
- Receives penis during sexual intercourse, and holds the spermatozoa before their passage to the uterus
- Lower portion of the birth canal through which the fetus passes
What can cause infertility?
STIs
Smoking (inhibits every step of reproduction)
Obesity (every step in female damaged)
Age at childbearing
What are the numbers of follicles and the statistics associated with them?
Born with 7 mil follicles
400 ovulated
2 result in a live birth
0 after menopause
What are the numbers of sperm and statistics associated with them?
1500 sperm produced per second per testicle: 300 million per day from puberty to 90yo
Sperm swim 15km to reach an egg.
What is the uterus?
Small, pear-shaped organ (30-40g).
Forms the pathway for sperm transport
Provides protection, nutrition and waste removal for embryo and fetus.
Contractions of myometrium result in fetal ejection
Source of menstrual flow
What is the structure of the endometrium?
Inner functional zone (stratum functionalis) containing uterine glands, and outer basilar zone, attaching the endometrium to the myometrium.
What does the stratum functionalis do?
Grows during each menstrual cycle, produces secretions for aiding embryonic survival. It is released during menstruation
What are the uterine tubes?
Oocytes are released onto the fimbriae of the uterine tube (fingerlike projections), and transported into the ampulla, where fertilization tends to occur.
The tubes contain lipids and glycogen, for spermatozoa, oocytes and embryos.
Lined with ciliated and nonciliated secretory columnar cells
Surrounded by layers of smooth muscle
Contraction of muscle via peristalsis and ciliar beating moves oocyte from ovary to uterus
What are the ovaries?
Oval organs, 5-10g. Comprised of outer ovarian cortex (containing follicles), central ovarian medulla (ovarian stroma, steroid producing cells), and inner hilum (point of entry for nerves/blood vessels
What is an ectopic pregnancy?
Embryo implants in the uterine tube
How can you tell weeks of pregnancy by size?
No. of cm above pubic bone = no of weeks pregnant
What are the stages of development of a follicle to an embryo?
Primordial Follicle Primary Follicle Secondary Follicle Mature Follicle Ovulation Corpus Luteum Fertilisation
What is the structure of a primordial follicle?
Single layer of flat follicular cells (squamous) surrounding the oocyte become granulosa cells.
This takes place within the ovarian cortex
How does the primordial follicle become a primary follicle?
The follicle grows, but still consists of only one layer of granulosa cells
Some cells respond to FSH and grow even larger, forming many layers of granulosa cells
The oocyte secretes glycoproteins, which form an acellular layer, the zona pellucida
Stromal cells around the follicle condense to form the thecal layer
How does a primary follicle become a secondary follicle?
Granulosa cells proliferate, producing a thick fluid, which comes together to form a single ‘antrum’. The theca interna and externa develops. The theca interna is highly vascular, and secretes oestrogen. The theca externa forms the outer protective layer of the follicle, and is fibrous.
The innermost granulosa becomes firmly attached to the zona pellucida
Loosely arranged granulosa cells surrounding this becomes the cumulus oophorous
How does a secondary follicle become a mature follicle?
Antrum grows, with the oocyte becoming suspended in fluid, attached by a stalk.
How does the mature follicle get ovulated?
The follicle increases even more in size, and moves to the edge of the cortex, causing a bulge. Eventually, the follicle ruptures, causing the oocyte and its surrounding cumulus to the uterine tube
How does the corpus luteum get formed?
The antrum breaks down, the basement membrane between the theca and granulosa breaks down, and blood vessels invade. Granulosa cells form lutein cells, which produce a yellow pigment (referred to as luteinisation).
This is associated with an increased secretion of progesterones, to allow pregnancy to occur.
If fertilization doesn’t occur, the corpus luteum disintegrates within 14 days. Whitish scar tissue remaining (corpus albicans) is reabsorbed into the stromal tissue of the ovary over weeks/months
What happens if the oocyte is fertilized?
The oocyte begins to divide, and the corpus luteum persists past its normal 2 week lifespan. hCG is produced by the embryo, which preserves it.
What are the two phases in the ovarian cycle, and how long do they stretch?
Follicular phase and luteal phase: Follicular is from day 1 to ovulation, while luteal is from ovulation to menstruation
What are the 3 phases of the endomentrial cycle?
Menstrual, proliferative and secretory.
What causes the proliferative phase?
Estrogens (Esp. oestrodiol) released by the theca externa
What causes the secretory phase?
Progesterone and estrogens secreted by the corpus luteum
How long is the luteal phase?
Always 14 days (it is the follicular phase that varies)
What does FSH act on?
All the follicles within the ovary
What does LH act on?
Secondary and mature follicles, ovulation staage, and corpus luteum
What and when are the fluctuations in the 4 main female hormones?
Small FSH peak approx. day 2-4, responsible for the commencement of follicle development
Large oestrogen peak around day 12, and then a smaller one around day 21
Large LH peak around day 14
Progesterone peak around day 22
How does the hypothalamus control follicles leading to ovulation?
- High levels of estrogens from near-mature follicles stimulate the release of more GnRH and LH
- GnRH promotes more FSH and LH (although inhibin prevents these rising too much)
- LH brings about ovulation
What is the zona pellucida?
A protective ring around the oocyte made of glycoproteins.
What are the main events of ovulation, starting from the regression of the corpus luteum, as well as their meanings? (10 steps)
- Corpus luteum regresses, low oestrogen and progesterone, and increased FSH
- FSH stimulation leads to increased follicular group as the next group of follicles develops
- Day 6-7, the most dominant follicle is selected, with increased oestrogen
- Oestradiol suppresses FSH and LH production in the ant. pituitary
- By day 10-12, a threshold concenration of oestradiol is exceeded. If it’s maintained for 36 hours, the feedback mechanism switches from negative to positive
- This positive feedback triggers a GnRH rise, leading to an LH spike
- LH surge induces ovulation
- Corpus luteum develops, and progesterone increases
- Elevated progesterone inhibits GnRH, decreasing FSH and LH
- Demise of the corpus luteum
What is androgen resistance syndrome?
- The androgen receptor is damaged, so the body appears female, but has a Y chromosome and internal male genitalia.
What is sex determination?
The commitment of an indifferent gonad to a testis or an ovary.
What determines whether a baby will be male or female?
The SRY (Sex-determining Region of the Y-chromosome) gene provides the pathway for the testis to develop. In the presence of the testis, a baby will always be male. Without it, it will always be female
What sex will an XXXY baby be and why?
Male, as the presence of a single Y chromosome outweighs all the Xs.
What happens if there is a mutation in the SRY gene, causing it to malfunction?
The baby will be female
What is sex differentiation?
The development of genital structures due to the action of hormones produced following gonadal development
What is the pathway to internal male genitals?
Mesoderm –> Bipotential gonad –(SRY)–> Leydig Cells —> Testosterone —> Wolffian Duct development —> Internal male genitals
Arrows mean the actively promote the next step.
What is the pathway to mullerian duct regression in males?
Testis–> Sertoli Cells —> Produce Anti Mullerian Hormone (AMH) –> Mullerian duct regression
What is the pathway to internal female genitals?
Mesoderm —> Bipotential Gonad—> Ovary —> Oestrogens, progestagens
Mullerian Duct Development—> Internal female genitals
Wolffian duct regression
What actively promotes the development of mullerian and regression of wolffian ducts in females?
Nothing- it’s the default process in embryos (w/o SRY)
What does the independence of female internal genitalia and hormones mean?
Female internal genitals will develop even without ovaries and female hormones.
What is the structure of the genitals at an undifferentiated stage of foetal growth?
Gonadal ridges on the inside, then mesonephros laterally, Wolffian duct laterally to this, and then Mullerian duct even more so. All structures are paired.
How do internal male genitals form from the wolffian duct?
Firstly, AMH causes the mullerian duct to regress. Testosterone secreted by the testis actively maintains the wolffian ducts.
These develop into the epididymis, vas deferens and seminal vesicle. (The testes). These descend to the scrotum after about the 7th month.
How do internal female genitals form from the mullerian duct?
This lags behind male development
From about 10 weeks, the wolffian ducts start to regress.
The mullerian ducts persist and develop into the fallopian tubes, uterus, cervix and upper vagina.
How do male external genitalia differentiate?
Urethral folds fuses, enclosing the urethra and forming the shaft of the penis
Labioscrotal swellings fuse at the midline to form the swelling. The genital tubercle expands to form the glans penis.
How do female external genitalia differentiate?
The urethral folds and labioscrotal swellings don’t fuse, forming labia majora and minora. The genital tubercle forms the clitoris
What causes undifferentiated genitals to become male?`
5-alpha testosterone
What happens if there is a lack of testosterone in terms of external genital development?
Fusion of urethral folds is not complete
What is puberty?
The physical, emotional and sexual transition from childhood to adulthood.
Why does puberty occur?
It leads to full secondary sex maturation, and capacity for reproduction.
What are the endocrine changes occurring during puberty, and when do they tend to occur?
Increase in plasma LH due to increase in GnRH
This occurs mainly at night, during sleep
In late puberty, daytime LH pulses increase, causing a rise in sex sterioids
What are the secondary sexual characteristics?
Female: Breasts, pubic hair, menarche
Male: Pubic hair, penis growth, testicle growth
In females: What is the progression of secondary sexual characteristics?
1st change: An increase in oestrogen causes the appearance of the breast bud due to follicles becoming mature (thus producing the oestrogen)
Ovulation and subsequent progesterone/oestrogen leads to full breast development
2nd change: Within 6 months of the breast buds, pubic hair arises due to hair follicles being exposed to androgens
3. Peak growth and epichyseal closure (sealing of bones to stop growth) is stimulated due to oestrogens and androgens
- Menarch: The first ovulation occurs about 6-9 months after first menarch, as the positive feedback mechanisms with oestrogen are not yet fully coordinated.
Regular cycles begin 1-2 years after first menarche.
In males: What is the progression of secondary sexual characteristics?
- Testicle enlargement occurs due to the enlargement of Leydig cells, which begin to produce testosterone.
- 6 months after testicle enlargement, pubic hair grows. Axillary hair appears 6 months after that
- Enlargement of the penis occurs approx. a year after testicles.
- Spermatogenisis: There are motile sperm in the urine at approx. 13-14 years old. The first conscious ejaculation occurs soon after.
What is body type determined by, and what are stereotypes of this?
They are determined by the effects of differing levels of androgens and oestrogens.
Males are tall, heavy and muscular
Females have fat distributed to their breasts and hips, with a modified pelvis for childbearing.
Why is the female age at puberty decreasing?
Probably due to the fact that you must hit a critical weight to undergo puberty, and the obseity epidemic means more children hit this date earlier- indicating that they are sufficiently able to carry a foetus and lactate safely.
What is precocious puberty?
The appearance of physical or hormonal puberty before (girls) 7yo and (boys) 9yo.
Why does precocious puberty occur?
It’s usually due to a GnRH dependent problem, such as a CNS lesion or injury
What is delayed puberty and what causes it?
Lack of the signs of puberty from:
13 years (girls)
14 years (boys).
Caused by insufficient GnRH relayed to the anterior pituitary.
What is menopause?
The last episode of natural menstrual bleeding, signifying the end of a female reproductive life.
What causes menopause and what are the hormonal changes associated with it?
Caused by the ovaries running out of follicles, occurring between 50-52 years old.
About a year after this, the ovaries have ceased to produce hormones, and oestrogen now comes from the stromal cells of adipose tissue in the form of oestrone (weak). Its production is about a tenth of previous.
What is pre-menopause?
Regular menstrual cycles
What is menopausal transition?
The period of time from the beginning of irregular cycles to the last cycle
What is peri-menopause?
It’s associated with symptoms, and lasts from the end of regular cycles to ovarian senescence
What is post-menopause?
Lack of cycles
What is ovarian senescence?
Ovaries have stopped producing hormones
What are the symptoms of menopause?
Vasomotor: hot flushes and night sweats
Genitourital symptoms: Atrophy, vaginal dryness
Bone metabolism: Osteoporosis
Psych changes: Depression, tension, confusion, anxiety, loss of libido
Why do the symptoms of menopause occur?
Estrogen deprivation
What can be done to treat the symptoms of menopause, and what are its risks?
Can be prevented or stopped by oestrogen treatment, but this may increase the risk of breast and cervical cancer.
Where does spermatogenesis occur?
Occurs in the seminiferous tubules, which house and produce the primordial sperm cells.
The process takes places across the radius of the seminiferous tubule: from the basal surface to the lumen.
What is the rate of sperm production in post-pubsecent males?
300-600 sperm per g of testes per second.
What are the 3 phases of sperm production?
Mitotic division
Meiotic division
Cyto-differentiation
How do spermatagonium become primary spermatocytes?
Spermatagoinia divide by mitosis, but asymmetrically: one daughter cell remains on the basement membrane, to keep as a stem cell.
The other daughter cell continues to divide by mitosis to form 4-8 spermatagoinia.
This occurs in the basal compartment of the seminiferous tubules, and the daughter cells still have 46 chromosomes.
Then, they force their way through the sertoli cells, held together by tight junctions, until they reach the adluminal compartment, next to the lumen. This is also called the intercellulus phases.
When they have forced their way through, they become primary spermatocytes.
How does a primary spermatocyte become a secondary spermatocyte?
Each of the primary spermatocytes then undergoes meiosis I, where the 46 chromosomes doubles and divides, producing 2 daughter cells with 46 chromosomes.
Then, these cells divide again, but this time each has 23 chromosomes. They are then called secondary spermatocytes.
How do secondary spermatocytes become spermatids?
The secondary spermatocytes divide rapidly, each producing four gametes. However, they are still fairly round.
How do spermatids become sperm cells (Spermatozoa)?
Called spermiogenesis. They move into the lumen of the seminiferous tubules, where excess cytoplasm is lost into a residual body to be phagocytosed by sertoli cells.
What are the 4 main parts of a sperm?
Head
Middle piece
Principal piece
Tail
What is the acrosome?
A covering over the head of the sperm, the interior of which is filled with enzymes for egg penetration.
How is spermatogenesis controlled by hormones?
The hypothalamus produces GnRH, which stimulates the anterior pituitary to produce FSH and LH.
LH goes to the leydig cells, encouraging them to produce testosterone, which produces 5-alpha and therefore codes for secondary sexual characteristics.
FSH goes to the sertoli cells, which are in direct contact with the spermatogonia, primary and secondary spermatocytes. This stimulates it to produce androgen binding protein (ABP), which binds to testosterone to keep its levels high in the testes and stimulate sperm development.
How does negative feedback play a role in spermiogenesis.?
The presence of testosterone in the blood inhibits LH and to some extent GnRH.
Sertoli cells produce inhibin, which inhibits the release of FSH.
What role does kisspeptin play in the hormonal control of sperm development?
It’s a neurotransmitter which regulates GnRH output from the hypothalamus, and the onset of puberty.
What is male infertility?
It occurs when men have less than 20million viable sperm per mL semen
It can be due to reduced sperm (oligospermia), no sperm (azoospermia) or immotility of sperm.
It’s more present in those with obesity and diabetes.
What are the treatments available for male infertility?
IVF:
- Oocytes are harvested, to be fertilized in vitro,
This requires approx. 50,000 motile sperm
ICSI:
- A single sperm is injected into the cytoplasm of an oocyte using a microfine pipette.
The sperm doesn’t even need to be motile, and can be harvested by biopsy.
Describe the testicles
Paired organs located in the scrotum
Connected via the inguinal canal to the pelvic canal
Divided in two by the raphe (externally) or septum (internally)
They are outside the body as sperm need a slightly cooler than body temperature to develop.
What makes up the inguinal canal?
Blood vessels, nerves, vas deferens and cremaster muscle (encasing it)
What is the name of the condition where the testicles do not descend?
Cryptochidism, which causes infertility
What is the endocrine and exocrine function of the testes?
Endocrine function: produces hormones
Exocrine function: produces sperm
What surrounds the testes, and what is its function?
The tunica albuginia: a white connective tissue covering
It also partitions the testicles into lobules, each containing 2-3 seminiferous tubules, where the spem is produced
What is the general pathway of sperm from production to ejaculation?
Seminal vesicle –> Rete testis (middle of testicle) –> epididymis (crescent shaped half of testicle) –> vas deferens –> Ampulla (joins ejaculatory duct, in the prostate area) –> Prostatic urethra –> intermediate urethra –> Spongy/penile urethra –> ejaculation
What is the epididymis, and what is its function?
Comma shaped portion of testicles
The place where the sperm develop the ability to swim (after 10-14 days of growth)
Sperm is concentrated as the epididymis absorbs liquid
Moves the sperm to the vas deferens for storage, using peristalsis
Lined with pseudostratified columnar epithelia and 3 layers of smooth muscle
What is the vas deferens?
A vessel which runs from the epididymis up and over the bladder to the ejaculatory duct in the urethra
What is the ampulla?
Little vase: it joins the ejaculatory duct with the vas deferens in the area of the prostate
Where does the urethra run?
from the bladder to the prostate, and then out of the penis.
What are the seminal vesicles and their function?
They are secretory glands, which secrete mucoid substances which are alkaline
It contains fructose, prostaglandins for inducing peristalsis in female reproductive tract, and clotting proteins
The fluid is emptied into the ejaculatory duct, joining the urethra at the prostate.
This occurs after the sperm has been ejected by the vas deferens, washing them down the ejaculatory duct
What is the prostate and what does it produce?
It is a donut shaped structure which the urethra passes through
It secretes prostatic fluid
What is prostatic fluid comprised of?
Citrate for ATP production Milky color due to Calcium Phosphate PSA for breaking down clotting coagulum Slight acidity
What is the breakdown of semen?
10% sperm
60% seminal fluid
30% prostatic fluid
small amounts of other secretions
What is the bulbourethral secretion?
A slightly alkaline fluid which comes through the urethra, removing the acidity from urine
What is the structure of the penis?
Most lateral: 2x corpora cavernosa, the main erectile tissue
Corpus spongiosum: surrounds the urethra and prevents the urethra from being squashed during erection
Penile urethra conducts semen and urine
How is erection maintained?
Hydrostatic pressure in the corpora cavernosa
Nitric Oxide causes the corpus cavernosa muscle to relax, allowing blood to fill them. Veins get squashed so blood can’t escape.
What does viagra do?
Inhibits the action of a phosphodiesterase responsible for breaking down cGMP (necessary for relaxation of the corpora cavernosa muscle),
What is BPH?
Benign prostate hyperplasia
- Excessive growth of the prostate, resulting in squashing of the urethra
- Trouble voiding and controlling the bladder, leading to UTIs and kidney issues
- Affects 90% over 85
- 2nd most common male surgery
What is treatment for BPH?
Surgery
Drugs inhibiting 5-alpha reductose, which turns regular testosterone in the the 5-alpha form
What are some features of prostate cancer?
2nd most common cause of male death
Detection increases by finding prostate-specific antigens
Deaths are increasing, but less steeply
The test isn’t that reliable- 2/3rds with prostate cancer don’t know they have it
What are some options for prostate cancer?
Waiting (many are benign) Androgen depletion Inhibition of 5-alpha reductose Castration Inhibition of androgen synthesis Inhibition of androgen receptors surgery
What are the outcomes for every 100 prostate cancer surgeries?
1 man dies
20-80 get erectile dysfunction
4-21 become incontinent.
