Section 4: Reproductive System Flashcards
Reproductive hormones - categories
Water soluble (peptides and proteins) Lipid soluble (steroid hormones)
Water soluble reproductive hormones - site of secretion
Gonadotrophin releasing hormone (GnRH) - hypothalamus
Follicle-stimulating hormone (FSH) - anterior pituitary
Luteinising hormone (LH) - anterior pituitary
Oxytocin - posterior pituitary
Lipid soluble reproductive hormones - site of secretion
Androgens - testes
Oestrogens - ovary
Progestagens - ovary
Main endocrine glands controlling reproductive processes
Hypothalamus
Pituitary gland
Adrenal glands
Ovary
Testes
Main functions of gonads
Produce gametes
Produce reproductive hormones
Regulation of gonadotrophin secretion
Hypothalamus —(+ve feedback, GnRH)—>
Anterior pituitary: gonadotrophs –>
FSH and LH –>
Gonads
Gonads use -ve feedback (sex hormones) on anterior pituitary and -ve feedback on hypothalamus
Sex steroids: Androgens - testosterone
Main secretory product of testis
Associated with development and maintenance of male characteristics and fertility
Sex steroids: Types of androgens
Testosterone
5-α-dihydrotestosterone
Sex steroids: Androgens - key properties
Male sex development
Spermatogenesis
Sexual behaviour
Muscle development
Types of oestrogens
Oestradiol
Oestrone
Oestriol
Oestrogens - main role
Development and maintenance of female characteristics and fertility
Oestrogens - main site of production
Granulosa cells of growing follicle
Oestrogens - key properties
Female sex development
Growth of endometrium
Regulation of menstrual cycle
Bone growth
Progestagens
Major steroidal hormone of corpus luteum and placenta
Associated with preparations for pregnancy and its maintenance - ensure to provide best environment for an embryo to implant after fertilisation
Helps maintain placenta and uterus throughout pregnancy
Gonads
Ovaries and testes
Is testosterone produced in females
Yes, but about 10x less than in males
Is oestrogen produced in males
Yes, but about 10x less than in females
Oestrogens - oestradiol
Main and most important oestrogen
Produced by granulosa cells in developing follicle
Produced from puberty to menopause
Oestrogens - oestrone
Produced throughout a women’s life and also produced by men
Always present post-menopause in women
A weak oestrogen
Oestrogens - oestriol
Produced by placenta just prior to labour
Helps with softening of cervix
Is progestogen produced in males
No
Sex determination
Commitment of the bipotential gonad to a testis or an ovary
Presence of a testis determines sexual fate of embryo, against the basic feminine trend
SRY gene
Sex-determining Region on Y chromosome
Provides pathway for testes to development
In absence of SRY, embryo develops into a female (by default)
Sex differentiation
The phenotypic development of genital structures due to action of hormones produced following gonadal development
How is sex determination in mammals controlled
Genetically controlled
Y chromosome present: male gonads develop (testes)
Y chromosome absent: female gonads develop (ovaries)
Sex differentiation: Internal genitalia - female and male names
Female = Mullerian duct Male = Wolffian duct
Primitive gonad
Indifferent - could become either a teste or ovary
Once decision is made, the phenotype of that organism develops around it
Internal genitalia: Undifferentiated stage
Very early on development; 5th-6th week embryo
Bi-potential gonad
Mullerian and Wolffian duct both present
Internal genitalia: Male differentiation
Mullerian duct regression under control of AMH
Testosterone secreted by testis (Leydig cells) actively maintain Wolffian ducts, which develops into the epididymis, vas deferens and seminal vesicles
Testis descends from its internal position to scrotum, usually after 7th month
AMH
Anti-mullerian hormone
Secreted by sertoli cells
Internal genitalia: Male differentiation - for males to be fertile…
The testes need to descend and appear on outside of body
Usually complete by ~7th month, but if not, then need help to get them out or will be infertile and have higher risk of testicular cancer
Internal genitalia: Female differentiation
Lags behind male organogenesis because no active hormones driving this process
Wolffian ducts begin to regress slowly from about 10 weeks
Mullerian ducts persist and develop to give rise to uterine (fallopian) tubes, uterus, cervix and upper vagina
Male and female external genitalia develop from..
A single bi-potential precursor
Male vs female external genitalia - hormones
Male external genitalia is driven by hormones, female genitalia doesn’t require active hormone intervention
External genitalia: Male differentiation
Fusion of urethral folds enclosing the urethral tube –> forms shaft of penis
Labioscrotal swelings fuse in mid-line –> forms scrotum
Genital tubercle (glans area) expands –> forms glans penis (tip)
External genitalia: Female differentiation
Urethral folds and labioscrotal swellings remain separate --> forms labia minora and majora Genital tubercle (glans area) forms clitoris
Has more similarity than males to what it began from
What hormone drives male differentiation
Androgens - forces changes in structures
External genitalia: Male differentiation - testes descend into…
Scrotum
Androgen insensitivity syndrome
Person is XY and has testes, but genital ducts and/or external genitals are female
Mutation in androgen receptor gene –> prevents androgen function
Puberty
The physical, emotional and sexual transition from childhood to adulthood
Transition is gradual and punctuated by well-defined events
Hormonal changes in puberty lead to…
Behavioural responses
Physical changes
Puberty - ‘reawakening’
Following activity in developing embryo to produce genitalia, reproductive system ‘goes to sleep’ during childhood
Puberty is ‘reawakening’ of reproductive endocrine systems –> full secondary sexual maturation with capacity for reproduction
Mechanisms keeping reproductive function on hold and those that trigger puberty
Largely unknown
Plasma levels of ____ are very low during childhood until initiation of events leading to puberty
Gonadotrophins
First endocrine sign of puberty
An increase in plasma LH levels, and is the result of an increase in GnRH release
Diurnal changes in pulsatile release of LH at puberty
Gonadotrophin secretion (LH and FSH) occurs in early puberty at night during sleep
In late puberty, daytime LH pulses also increase
Sex steroids rise in response to increase in plasma LH
Secondary sexual characteristics - timeline
Develop at diff chronological ages in diff individuals
Sequence in which changes occur are quite characteristic for each sex
Tanner stage
Staging criteria that allows abnormalities to be detected, and comparisons made between individuals
Females: Sequence of events during puberty
- Breast
- Pubic hair
- Height spurt
- Menarche
Females: Breast development
First sign of secondary sexual maturation at age ~10-11
Oestrogen secretion leads to appearance of breast bud, followed by formation of a breast mound
Ovulation, with subsequent progesterone secretion, leads to full breast development
Females: Sexual hair development
Usually within 6 months of appearance of breast bud at age ~10-12
Due to exposure of hair follicles to androgens
Axillary hair follows ~1 years after pubic hair
Growth spurt
Stimulated by steroid hormones (oestrogen and androgen) with epiphyseal closure (bony ends) by oestrogen
Girls age ~11-12
Boys age ~13-15
Females: Menarche
Average age 12-13 years
First ovulation doesn’t take place until 6-9 months after menarche because +ve feedback mechanisms of oestrogen haven’t developed
Regular ovulatory cycles established 1-2 years after menarche
What does the first menstrual bleed (menarche) show
Doesn’t ensure the female is fertile, just shows the reproductive system has begun
Females: Pubic hair development before breast development
If pubic hair development occurs much before breast development, might indicate an androgen disorder
Axillary hair
Armpit hair
Males: Sequence of events during puberty
- Testis
- Pubic hair
- Penis
- Height spurt
Males vs females: Spermatogenesis and ovulation
Spermatogenesis begins earlier than ovulation does in females
Males: Testicular and penile enlargement
First signs of secondary sexual development is enlargement of testicles
Leydig cells enlarge and secrete testosterone –> gives rise to increased testicular size
Elongation and enlargement of penis begins within a year of testicular enlargement
Males: Sexual hair growth
Pubic hair appears ~6 months after beginning of testicular enlargement
Axillary hair begins ~18 months later, and facial hair later
Males: Spermache
Motile sperm is seen in urine at ~13-14 years
First conscious ejaculation occurs soon after
Equivalent of female ovulation - achieves fertility
Body shape in boys and girls is determined by differential effects of…
Androgen and oestrogen
Timing of puberty - females
A critical weight must be attained before activation of hypothalamo-pituitary-gonadal axis can occur
~47kg
Decreasing age of puberty in females
Attainment of a critical weight due to improvements in nutrition, healthcare and social living conditions
Signifies sufficient storage is required to sustain pregnancy and lactation
Precocious puberty
Appearance of physical and hormonal signs of puberty before:
7 years in girls
9 years in boys
Usually due to a GnRH dependent problem, often due to hypothalamic tumour
More common in females
Delayed puberty
Lack of appearance of physical and hormonal signs of puberty
13 years in girls
14 years in boys
Occurs when gonadotrophin signals from pituitary are inadequate for sex steroid hormone secretion
More common in males
Menopause
The consequence of ovaries running out of follicles
The last episode of natural menstrual bleeding signifying the end of a female’s reproductive life
What age does menopause occur
Between 50-52 years of age
Stages of menopause
Pre-menopause - regular cycle
Menopausal transition - irregular cycle
Post-menopause - after last menstrual cycle
Perimenopause - menopausal transition + ~1 year
Ovarian senescence - when ovaries stop working (don’t stop working immediately after menopause)
Post-menopausal oestrogen production
By ~1 year after menopause, ovary has essentially ceased producing hormones (ovarian senescence)
Oestrogen production reduces to less than 1/10 of previous
Oestrogen (oestrone) arises mainly from production in stromal cells of adipose tissue
Perimenopausal symptoms are due to…
Oestrogen deprivation
Perimenopausal symptoms
Vasomotor: - hot flushes - night sweats Genitourinary symptoms: - atrophic changes - vaginal dryness --> often pain during intercourse Bone metabolism: - osteroporosis (bone disease/weakness) Behavioural/psychological changes - depression, tension, anxiety, mental confusion - loss of libido
Treatment of perimenopausal symptoms
Most symptoms may be prevented or arrested by oestrogen treatment
How many oocytes are released in the average female
Few
~400
Mature oocyte is released every __ days
~28
Anteflexion vs retroflexion
Most women have an anteflexed uterus - uterus is 90 degrees to angle of vagina
~20% of women will have a retroflexed uterus, which could cause some pain during menstruation or intercourse, but usually becomes anteflexed after pregnancy
Vagina - structure
An elastic muscular 7.5-9.0 cm tube extending from the cervix to the exterior of the body
Vagina - main functions
Passageway for elimination of menstrual fluids
Receives penis during sexual intercourse and holds spermatozoa before they pass into uterus
Forms lower portion of birth canal through which the fetus passes during delivery
Vagina - bacteria
Has a very acidic environment to ensure bacteria are destroyed
Uterus - structure
Small, pear-shaped organ
Has a tapering body down the side
Has multiple muscle layers
Predicting fetal growth
Uses fundal height - top of the uterus to pubic bone
Number of cm is approx the no of weeks of gestation
Predicting fetal growth: Fundal height - larger than expected could mean…
Twins
Breech birth
Gestational diabetes
Uterus - main functions
Pathway for sperm transport
Mechanical protection, nutritional support, and waste removal for developing embryo and fetus
Ejection of fetus at time of birth
Source of menstrual flow
Uterus: Myometrium - function
Contractions in muscular wall (myometrium) of uterus are important in ejecting fetus at time of birth
Uterus: Endometrium can be subdivided into…
Inner functional zone (stratum functionalis)
Outer basilar zone (stratum basalis)
Uterus: Endometrium - Inner functional zone
Contains most uterine glands - able to provide nutrition to developing embryo
Lost through menstrual cycle - entire thickness is lost, then increased growth in response to oestradiol, and becomes secretory
Uterus: Endometrium - Outer basilar zone
Adjacent to myometrium
Attaches endometrium to myometrium
Not lost during menstruation
Uterine/fallopian tube - function
Provides a rich, nutritive environment containing lipids and glycogen, for spermatozoa, oocyte, and the developing embryo
Where does fertilisation typically occur
In the ampulla
Uterine/fallopian tube: Epithelium lining
Epithelium lining of uterine tube has both ciliated and non-ciliated secretory columnar cells
Uterine/fallopian tube: Mucosa
Surrounded by concentric layers of smooth muscle
Transport along the uterine tube involves…
A combination of both ciliary movement and peristaltic contractions
Ectopic pregnancy
When the fertilised embryo is implanted in any tissue other than the uterine wall
Where do most ectopic pregnancies occur
Uterine tube
Called tubal pregnancy
Ectopic pregnancy - risk factors
Smoking
Advanced maternal age
Prior tubal damage
Ovary - structure
Oval shaped
Often white/yellow, sometimes lumpy and flattened
Ovary - regions
Outer ovarian cortex - contains ovarian follicles Central ovarian medulla - consists of ovarian stroma and steroid producing cells, which eventually become thecal cells Inner hilum (hilus) - acts as a point of entry for nerves and blood vessels
Primordial follicle
The oocyte once surrounded by follicular/granulosa cells form the primordial follicle
Appear as little nests/clumps
Single layer of flattened squamous granulosa cells
Everyday, some grow, but most die
Primary follicles - structure
Increase in size of oocyte
Immature primary follicles consist of only one layer of cuboidal granulosa cells
Primary follicle: Zona pellucida
A translucent acellular layer formed by glycoproteins secreted by the oocyte
Layer between oocyte and granulosa cells
Contain receptors - allows entry of only one sperm
Primary follicle: Thecal cells
Condensation of ovarian stromal cells (known as thecal cells) that begin to form around the follicle
Follicle development
In response to FSH, some follicles get larger, producing many layers of granulosa cells surrounding the oocyte
Secondary follicle
AKA antral follicle
As granulosa cells proliferate, they produce a viscous follicular fluid that coalesces to form a single follicular antrum - called secondary/antral follicles
Secondary follicle: Corona radiata
Where the innermost layer of granulosa cells become firmly attached to the zona pellucida
Secondary follicle: Cumulus oophorus
Mass of loosely associated granulosa cells around the corona radiata
Cloud-like structure
Secondary follice: Theca interna and externa
Theca develops to become the inner glandular, highly vascular ‘theca interna’, and the surrounding fibrous capsule, the ‘theca externa’
Mature follicle AKA…
Graffian follicle
Pre-ovulatory follicle
Mature follicle
As follicular antrum grows, oocyte becomes suspended in fluid
Connected to rim of peripheral granulosa cells by a thin stalk of cells
Ovulation - structure
The increasing size of follicle and its position in the cortex of the ovarian stroma causes it to bulge out from the ovarian surface
Ovulation
Follicle ruptures, carrying with it the oocyte and its surrounding mass of cumulus cells
Slow and carefully managed process - 10-15 mins for an oocyte to be released
Involves enzymes
Ovulation - the oocyte is collected by…
Cilia on the fimbria, which sweep the cumulus mass into the uterine tube
Corpus luteum
Formed by granulosa cells
Initially was an empty follicle
If no fertilisation, it stays present for only 2 weeks, then degenerates to become the albicans, and the empty follicle is absorbed back into the ovary in a few weeks/months
Luteinisation
Where the antrum breaks down, the BM between the granulosa and thecal layers break down, and blood vessels invade
Associated with an increasing secretion of progestagens
Corpus albicans
The white-ish scar tissue remaining
Absorbed back into the stromal tissue of the ovary over weeks to months
If fertilisation doesn’t occur, cycle starts all over again
Corpus luteum: If the oocyte is fertilised and begins to divide…
The corpus luteum persists past its normal 2 week lifespan
Fertilisation: What is the corpus luteum ‘rescued’ by?
It’s rescued from degeneration by hCG
hCG
Human Chorionic Gonadotropin
Produced by the chorion of the embryo about 8 days after fertilisation
hCG in blood / urine
The presence of hCG in maternal blood or urine is an indicator of pregnancy and is the hormone detected by home pregnancy tests
Ovarian cycle - phases
Follicular phase (day 1 to ovulation) Luteal phase (ovulation to menstruation)
Uterine/menstrual cycle - phases
Menstruation
Proliferative
Secretory
Variation in length of menstrual cycle
Length of luteal phase usually 14 days - phase with least variation
Length of follicular phase is variable, and decreases as a woman ages
Female reproductive system - summing up
- Corpus luteum regresses, oestrogen and progesterone levels are low, increased FSH
- FSH stimulation leads to increased follicular growth
- Day 6-7, see selection of dominant follicle, with increased oestradiol
- Oestradiol suppress FSH and LH production in pituitary
- Oestrogen levels rise, by day 12, a threshold conc of oestradiol is exceed. If this is maintained for ~36 hours, there is a temporary switch from a -ve to +ve feedback
- Oestrogen-mediated +ve feedback triggers a rise in GnRH –> LH surge
- LH surge induces ovulation
- Corpus luteum develops, see increased progesterone
- Elevated progesterone levels inhibit GnRH –> decreased FSH and LH
- Demise of corpus luteum
High levels of oestrogen exert a ___ feedback on the ______, thereby increasing secretion of ____
Positive
Hypothalamus and anterior pituitary
GnRH and LH
Follicle development - phases
Primordial follicle –> primary follicle –> secondary follicle –> mature follicle –> ovulation
Connection of reproductive organs in females
Ovary is loosely connected to uterine tube, which enters the uterus
At base of uterus is the cervix, which protrudes partly into the top of the vagina
Vagina is separate from rectum on one side, and urinary bladder on other side
Which structure picks up immature ovaries produced by the oocyte
Fimbriae (finger-like structures) on the end of the uterine tube
Do all sperm reach the ovaries
No - many get lost along the way and get stuck in crypts or in the uterus
The embryo that is fertilised will implant into….
The side of the uterus (endometrium)
Uterus: Fundus
Top part of uterus
Where does the uterus end
In the cervix
Cervix
A constriction at the bottom, between the internal os and external os
Cervix - function
For most of the reproductive cycle, it’s filled with a plug of mucous so no sperm and bacteria can enter through the vagina into the uterus
For a few days prior to ovulation each month, the mucous changes to allow entry of sperm
Pathway of oocyte release
Ovary –> infundibulum –> uterine tube –> if sperm around, fertilisation takes place at ampulla
Uterine tube - fimbriae
Covered in cilia
Beating nearly constantly
Increases frequency of beating towards ovulation
Important for collecting oocyte once ovulated
What type of cells does the uterine tube contain
Lots of secretory cells - provides nutrients required for gametes and embryos to survive
Ovary - main functions
Produce oocytes and reproductive hormones
Tumours in ovary
Extremely large ones tend to be benign - don’t kill, just need to be removed
Others may be lethal
The majority of the ovary is stacked of…
Primordial follicles
Secondary follicle: Granulosa cells
Begin to specialise
The ones immediately around the oocyte = corona radiata
Fertilisation: Futile cycle
Oocyte produced
Corpus luteum produced and stays in place for 2 weeks
Progesterone is produced, but not embryo
Corpus luteum dies
Endometrial layer is lost by menstruation
Fertilisation: Fertile cycle
Oocyte produced
Sperm comes along
Makes embryo
After 8 days, embryo makes hCG
Corpus luteum produced and is rescued from death and remains
Layer of endometrium stays stable (not lost by menstruation)
Embryo can implant
Where does spermatogenesis take place
In the seminiferous tubule
Seminiferous tubule - structure
Has a BM
Interstitial cells between seminiferous tubules
Have cells inside the tubule
- many tails of mature sperm hanging out into lumen of tubule
- morphology of cells lining the tubule change as they move into lumen of tubule - mostly pre-sperm cells
Seminiferous tubule: Sertoli cells - structure
Run from BM through all the cells into the lumen
Connected to each other around perimeter of seminiferous tubule
In intimate contact with sperm and pre-sperm
Spermatogenesis - steps
Spermatogonia / stem cell (2n) --> Primary spermatocyte (2n) --> Secondary spermatocyte (n) --> Spermatid (n) --> Sperm cell / spermatozoon (n)
Sertoli cells for sperm are a bit like..
Granulosa cells for female oocytes
Where does spermatogenesis take place
In seminiferous tubules of testes
When does spermatogenesis occur
Only occurs after puberty
Huge numbers of sperm are produced constantly by the mature male; 300-600 sperm/gram of testis tissue/sec
Spermatogenesis - phases
Mitotic division
Meiotic division - sexual division
Cytodifferentiation - change from a round to elongated cell
Spermatogenesis: Spermatogonial stem cells
At puberty, primary germ cells are reactivated by endocrinal activity –> spermatogonial stem cells
Spermatogenesis: Division of spermatogonia - process
Divides by asymmetrical mitosis
1 daughter cell remains undifferentiated - maintains stem cell pop
Other daughter cell continues to divide by mitosis, forming spermatogonia, which continue to divide by mitosis
Spermatogenesis: Division of spermatogonia - place
Occurs in basal compartment of seminiferous tubules
Spermatogenesis: When mitotic divisions of spermatogonia occurs…
They move between adjacent sertoli to adluminal compartment of seminiferous tubules –> they are then called primary spermatocytes
Spermatogenesis: Division of primary spermatocytes
Meiosis I
DNA content doubles
Primary spermatocytes divide to produce secondary spermatocytes
Spermatogenesis: Where do spermatogonia sit
On BM
Spermatogenesis: Sertoli cells - function
Divide basal compartment from other two compartments of seminiferous tubules
Spermatogenesis: Where does each type of division occur
Spermatogonia = mitotic division Spermatocyte = meiosis Spermatids = cytodifferentiation
Spermatogenesis: Division of secondary spermatocytes
Divide rapidly via meiosis II - gives 4 spermatids each with 23 chromosomes
Spermatogenesis: Number of chromosomes in primary and secondary spermatocytes
Primary starts with 46
Secondary have 23
Spermatogenesis: Spermiogenesis - takes place when
Takes place with round spermatids still in close proximity and attachment to Sertoli cells
Cytodifferentiation AKA
Spermiogenesis
Spermatogenesis: Spermiogenesis
Final process in spermatogenesis
Round spermatids differentiate the shape and become spermatozoa / sperm –> moves into lumen of seminiferous tubules
Main function of sperm
To swim through female reproductive tract - has a number of diff adaptations to facilitate this
Spermatogenesis: Spermiogenesis - structure
Round spermatids form a tail, a mid-piece, and a head
Mid-piece packed with mitochondria to produce energy
Head contains DNA and is covered by the acrosome
Spermatogenesis: Spermiogenesis - Acrosome
A compartment filled with enzymes that are required for egg penetration
Has receptors that binds to shell of oocyte, and enzymes digest the shell so sperm can penetrate and get through to the oocyte
Spermatogenesis: Spermiogenesis - cytoplasm
Excess cytoplasm of spermatid is lost into the residual body that is phagocytosed by Sertoli cells after the sperm leaves
Spermatogenesis: Spermiogenesis - hydrodynamically adapted
Sheds all things unnecessary for swimming and fertilisation of egg, e.g. ER, Golgi, excess cytoplasm
Hormonal control of spermatogenesis: LH
A protein hormone
Secreted from gonadotrophs and go to testes, where LH interacts with Leydig cells –> produces testosterone –> dihydrotestosterone (DHT) –> secondary sexual characteristics
Male: Where do Leydig cells sit
In interstitial space between seminiferous tubules
Males: Hormonal control of spermatogenesis: FSH
Travels freely in blood down to testes, then binds to receptors on Sertoli cells, which start producing androgen binding protein (ABP)
Hormonal control of spermatogenesis: Androgen binding protein (ABP)
Since testosterone is a lipid hormone, it doesn’t mix with water/blood
ABP makes it soluble by binding to it –> allows testosterone and other androgens to be transported around the body
A small amount is secreted into seminiferous tubules –> testosterone can freely move across cell membrane –> support production of sperm
Spermatogenesis: Spermatogonia in final stages
Spermatogonia can’t progress through final stages, so a lack of testosterone causes infertility in males
Hormonal control of spermatogenesis: Testosterone and DHT - other effects
Aggressiveness, libido etc.
Too much is bad, so there is a control/endocrine system
- -ve feedback; testosterone feeds back to hypothalamus –> down-regulation of GnRH
- also feedback by testosterone at level of anterior pituitary; down-regulates production of FSH and LH
Hormonal control of spermatogenesis: Inhibin
A protein activated by binding of FSH to Sertoli cells
Goes back to anterior pituitary to regulate production of FSH (not LH)
Hormonal control of spermatogenesis: Kisspeptin
A hormone that binds to GnRH receptors in hypothalamus and stimulates production of GnRH
Common features of infertile men
Reduced sperm count
< 20 million / mL
Causes of male infertility
Oligospermia - some but limited sperm
Azoospermia - no sperm
Immotile sperm - can’t swim
Treatments for male infertility
IVF - in vitra fertilisation
ICSI - IntraCytoplasmic sperm injection
Treatments for male infertility: IVF
Oocytes are harvested, put in IVF droplets, and fertilised ex vivo
Requires approx 50,000 motile sperm
Helps treat men who are oligospermic
Treatments for male infertility: ICSI
Suck out sperm from testes using a micropipette
A single sperm is injected directly into oocyte
Sperm doesn’t need to be motile
Can use sperm collected by biopsy from testes
Treats men who are completely infertile
Orchidectomy
Removal of a testis
Cryptorchidism
If testes don’t descend
Cryptorchid individuals are infertile
Pathway of sperm
Produced in seminiferous tubules --> rete testis --> epididymis --> (ampulla) vas deferens --> urethra
How many seminiferous tubules in each testes
~80
Rete testis
An assembly of seminiferous tubules that come together and start to form into a single tube (epididymal tubule), which enters the epididymis
From here on, there’s only one tube carrying sperm away to the vas deferens
How long do sperm spend in the epididymis
10 days to 2 weeks transitioning along the epididymis
What abilities to sperm acquire in the epididymis
Ability to be motile
Ability to fertilise
Reabsorb liquid from around the sperm making it more concentrated (~100 fold)
Acquiring these abilities takes 10-14 days
How long can sperm be stored in the vas deferens
Several months - evolutionary advantage
Do sperm have ability to swim in the seminiferous tubule
No - only gain ability to swim in epididymis
Where is the major site of sperm storage
Vas deferens
Ejaculatory duct - pathway
Starts at end of vas deferens, then runs through prostate gland –> prostatic urethra –> penis –> exterior of male body
Vas deferens - length
~45cm
Where does the vas deferens run
From the epididymis up and around the bladder
Then back down to join the ejaculatory duct
Where do the seminal vesicles empty into
The ejaculatory duct, which joins the urethra at the prostate
Males: Urethra - length
~20cm long
Males: Urethra - pathway
Runs from bladder through the prostate to the end of the penis
Seminal vesicles
Secretory glands (not storage areas) that secrete a mucoid substance containing:
- alkaline
- fructose
- prostaglandins
- clotting proteins
Seminal vesicles - prostaglandin
Signalling molecule
May induce contractions in female reproductive tract
Seminal vesicles - clotting proteins
Once ejaculation takes place in female reproductive tract, the semen forms a coagulum, which sticks the sperm into the female reproductive tract
What is the last component that is ejaculated in males
The contents of the seminal vesicles
Prostate - structure
A donut-shaped organ about the size of a golf ball
Prostate - prosthetic fluid
The urethra passes through the prostate which secretes prostatic fluid into the urethra ahead of sperm during ejacuation
What does the prostate secrete
Slightly acidic (pH 6.5) Contains citrate (for ATP) Milky colour Phosphate and calcium PSA and other enzymes
PSA
Prostate specific antigen
Breaks down post-ejaculation coagulum ~10-15 mins after its formed –> allows sperm to swim
How is the acidity of prostatic fluid neutralised in semen
By seminal vesicle fluid (alkaline)
Order of ejaculate
- Prostatic fluid
- Sperm
- Seminal vesicle fluid
Males: What would happen if coagulum remains in place
Sperm wouldn’t be able to swim out of it and into the cervix / uterus
What is semen
The combined components of ejaculate
i.e. mixture of sperm and seminal fluid
What is semen made up of (%)
Sperm 10%
Seminal vesicle fluid 60%
Prostatic fluid 30%
Other secretions - small amounts
Semen pH
~7.5
Prostatic fluid and seminal fluid neutralise each other
Buffered to allow it to survive long enough in the female reproductive tract
Why does semen have a large volume of seminal vesicle fluid
Helps wash sperm down the reproductive tract
Males: Benign prostatic hyperplasia (BPH)
Excess growth of the prostate / prostatic tissue –> occludes urethra
Causes difficulty in voiding bladder
Eventually causes weakening of bladder
Can cause urinary infections and kidneys problems
Where does the prostatic urethra run through
The centre of the prostate
Pathway of urine and BPH
To urinate, urine must pass through the prostatic urethra to reach the urine urethra
So, when the prostate grows excessively and expands out against its capsule, any additional growth has to be inwards –> starts to occlude urethra –> difficulty urinating
Incidence of men requiring treatment for BPH
<40 is very rare
Starts increasing with increasing age
90% men over 85 years will need treatment
Benign prostatic hyperplasia (BPH): Treatments
Selective 5-α-reductase inhibitor(s)
- finasteride
- dutasteride (stops prostate enlarging or shrinks it, must be on drugs for a long time)
Surgery - transurethral section of prostate
Others - prostatic urethral lift
Function of 5-α-reductase
Converts testosterone to dihydrotestosterone
Potency of dihydrotestosterone
2x more potent than testosterone
__% of cancer cases in men are prostate
29%
Detection vs deaths of prostate cancer
Detection of prostate cancer increased dramatically (PSA testing) but deaths increased less dramatically
Prostate cancer: Autopsy cancer
30% of men > 50 y/o have prostate cancer at autopsy
But only 9.5% have been diagnosed with prostate cancer
i.e. 2/3 of men with prostate cancer don’t know they have it (isn’t causing any problems)
Detecting prostate cancer
Men can be screened for elevated levels of PSA
May allow early detection, but also ‘over-diagnosis’
What to do if someone has prostate cancer
Watchful waiting - do nothing, but monitor the tumour Androgen depletion - 5-α-reductase inhibitors - castration - inhibitors of androgen synthesis Inhibition of testosterone action - block androgen receptor Surgery - prostatectomy Others
Prostate cancer: Prostectomy
Removal of prostate gland by surgery
Proportion of men with +ve tests for PSA vs those with cancer
Of those who test positive, a large proportion of them will have a false +ve test result (i.e. no cancer)
Penis - major structures
Corpora cavernosa (x2) - main erectile tissue
Corpus spongiosum - surrounds penile urethra and prevents occlusion during erection
Penile urethra - conducts semen and urine
Penis - erection
Occurs following sexual stimulation
Release of NO and prostaglandin –> corpora cavernosa relaxes
Blood fills cavernous spaces of corpora cavernosa
Engorgement of corpora reduces venous outflow adding to the engorgement
Erect vs flaccid penis - blood
Erect penis contains ~8x the blood volume of the flaccid penis
Why does the corpora cavernosa relax when penis is erect
Causes walls to relax –> easier for blood to flow in
balloon analogy - stretch before blowing
Erect penis: Why is it important for the corpus spongiosum to also fill with blood
Important in maintaining openness of penile urethra during ejaculation
Viagra - sildenafil
Relaxation of smooth muscle in corpora cavernosa requires guanosine monophosphate (cGMP)
Enzymes phosphodiesterase breaks down GMP
Viagra inhibits phosphodiesterase (type 5) –> increased GMP –> relaxation of arteries supplying corpora cavernosa –> erection
Urethral folds
Develop from mesoderm in cloacal region
Urethral groove
An indentation between the urethral folds
The opening into the urogenital sinus
Genital tubercle
A rounded elevation just anterior to the urethral folds
Labioscrotal swelling
Consists of paired, elevated structures lateral to the urethral folds
Male: Scrotum
The supporting structure for testes
Consists of loose skin and underlying subcutaneous layer that hangs from the root of the penis
Male: Scrotal septum
Divides the scrotum into 2 sacs, each containing a single testes
The seminiferous tubules contain these two types of cells
Spermatogenic cells
Sertoli cells
Males: Interstitial cells AKA
Leydig cells
Most sperm do not survive more than __ hours in the female reproductive tract
48
Site of sperm maturation
Epididymis
Males: Vas deferens AKA
Ductus deferens
Males: Spermatic cord
Supporting structure
Ascends out of scrotum
Consists of vas deferens
Varicocele
A swelling in the scrotum due to a dilation of the veins that drain the testes
Usually more apparent when person is standing and typically doesn’t require treatment
Males: Bulbourethral/cowper’s glands - structure
Located inferior to prostate on either side of membranous urethra
Ducts open into spongy urethra
Males: Bulbourethral/cowper’s glands - function
During sexual arousal, they secrete an alkaline fluid into the urethra that protects the passing sperm by neutralising acids from urine in the urethra
Secrete mucous that lubricates the end of the penis and lining of urethra –> decreases no of sperm damaged during ejaculation
Ejaculation
The powerful release of semen from the urethra to the exterior
A sympathetic reflex coordinated by the lumbar portion of the spinal cord
Emission
The discharge of a small volume of semen before ejaculation
What do Sertoli cells produce
Androgen-binding protein (ABP)
During the menstrual cycle, what is progesterone produced by
Corpus luteum
What do interstitial cells (of Leydig) secrete
Testosterone
During the menstrual cycle, when is the endometrium at its thickest
Late in the post-ovulatory phase
During the menstrual cycle, when are LH levels at its highest
Just prior to ovulation
What are the interstitial cells of the testes an important target for
LH
Main function of progesterone during menstrual cycle
Thicken and maintain thickness of endometrium
In the male, LH causes…
Testosterone production
What is testosterone produced by
Interstitial (Leydig) cells
If fertilisation does not occur, the corpus luteum..
Degenerates into the corpus albicans
When does oogenesis begin in females
Before birth
What does the acrosome of a sperm cell contain
Hyaluronidase for egg penetration
What is repair of the endometrium during the preovulatory phase of menstruation due to
Rising levels of oestrogen
During the menstrual cycle, when is progesterone at its highest levels
Late in postovulatory phase
Which branch of the ANS is initiation and maintenance of an erection mained by
Parasympathetic
Theca interna contains…
Secretory cells
What happens just prior to ovulation
Oestrogen-mediated positive feedback triggers a rise in GnRH –> LH surge
