Module 4 - Reproduction Flashcards
What does the ovary contain
- stromal matrix
(connective tissue,
nerves, lymphatic and
blood vessels) - follicles
- tunica albuginea
- surface epithelium
List the stages of Ovarian Follicles during Folliculogenesis
- primordial follicles (non-growing)
- preantral follicles (early growing)
- early antral follicles
- antral follicles
Describe Primordial to preantral
stages:
- Gonadotropin INDEPENDENT i.e. no exogenous factors
- Intraovarian/paracrine factors
- Balance of stimulatory (activation/recruitment) and
inhibitory (quiescence/apoptosis) factors
Describe Early antral and beyond stage
- Gonadotropin DEPENDENT i.e. FSH and LH
- Follicle cells acquire FSHR and LHR
- Dominant follicle is selected
- Some regulation by intra-ovarian factors (inhibin and activin)
➢ via +ve and –ve feedback loops
When does the preantral stage occur in the menstrual cycle
Throughout
When does the very early antral stage occur in the menstrual cycle
throughout
When does the early antral stage occur in the menstrual cycle
1-6
When does the expanding antral stage occur in the menstrual cycle
6-10
When does the expanded antral stage occur in the menstrual cycle
10-12
When does the preovulatory stage occur in the menstrual cycle
13-14
Overview of meiosis
Prophase I
Metaphase I
Anaphase I
Telaphase I
Prophase II
Metaphase II
Anaphase II
Telaphase II
Define meiosis
Meiosis is a type of cell division that occurs in sexually reproducing organisms and reduces the number of chromosomes in gametes (the sex cells, or egg and sperm).
- During meiosis, the four daughter cells produced are haploid, meaning they only have half the number of chromosomes of the parent cell
- Meiosis produces our sex cells or gametes (eggs in females and sperm in males)
- Meiosis II is an equational division analogous to mitosis, in which the sister chromatids are segregated, creating four haploid daughter cells
FOLLICULOGENESIS
growth and
development of the follicle. it accompanies and supports oogenesis
OOGENESIS
growth and maturation of
the oocyte
Events of oogensis
- Before birth EVENTS
At birth, all
primordial follicles
are already present
and contain primary
oocytes arrested in
prophase I. - Throughout life
until menopause
Primordial follicles
begin to grow and
develop. (Before
puberty all
developing follicles
undergo atresia.) - From puberty to
menopause
After puberty, some
antral follicles are
rescued from atresia
each month and the
primary oocyte in one
(the dominant follicle)
completes meiosis I.
Regulation of the ovarian cycle
- GnRH stimulates FSH and LH secretion
- FSH and LH stimulate follicles to grow,
mature and produce steroid hormones
2-cell 2 gonadotropin hypothesis - Negative feedback inhibits gonadotropin
release - Positive feedback stimulates
gonadotropin release
- Estrogen levels continue to rise as a result
of continued release by dominant follicle
- When levels reach a critical high value, a
brief positive feedback occurs on brain and
anterior pituitary
- Triggers LH surge - LH surge triggers ovulation and formation
of the corpus luteum
- LH surge triggers primary oocyte to
complete meiosis I to become the secondary
oocyte
- Secondary oocyte enters meiosis II and
arrests at metaphase II
- Shortly after ovulation:
Estrogen levels decline
LH transforms ruptured follicle into corpus
luteum
LH stimulates corpus luteum to secrete
progesterone (and some estrogen)
almost immediately - Negative feedback inhibits LH and FSH
release
- Negative feedback from rising plasma
progesterone and estrogen levels
- Inhibin enhances inhibitory effect
- Declining LH inhibits follicle development
- If no fertilisation occurs:
* Corpus luteum degenerates
* Sharp decrease in progesterone and
estrogen
* Ends the negative feedback and cycle
starts again
The uterine (menstrual) cycle
Cyclic changes in the endometrium that occur in response to fluctuating ovarian hormone levels
Three phases:
1. Days 1–5: menstrual phase
2. Days 6–14: proliferative (preovulatory) phase
3. Days 15–28: secretory (postovulatory) phase
Days 1–5: menstrual phase
- Gonadotropin levels beginning to rise
- By day 5, growing follicles starting to
produce more estrogen - Functional layer of the endometrium shed
Days 6-14: proliferative phase
- LH steadily rising with surge just before
ovulation - FSH declining with increase just before
ovulation - Rising estrogen levels → regeneration of
the functional layer of the endometrium - Ovulation at end of the proliferative phase
on day 14.
Days 15-28: secretory phase
- Begins immediately after ovulation
- Most consistent in duration
- Drop in LH, but level still high enough to
support progesterone (P) production by
corpus luteum - P promotes well-developed blood supply
and endometrial glands provide nutrientrich secretions to prepare for implantation - P thickens cervical mucus to form a plug
that blocks entry of more sperm,
pathogens or debris - If corpus luteum degenerates, P causes
spiral arteries in endometrium to constrict
and endometrial tissue dies
why does the female cycle have 2 phases
The two phases of the female cycle are necessary for the preparation of the uterus for pregnancy and the release of an egg for fertilization. The follicular phase prepares the egg for release, while the luteal phase prepares the uterus for implantation of a fertilized egg.
Identify some actions of estrogen and progesterone on reproductive
organs
- stimulate growth and maturation of reproductive organs and breasts and maintain their adult size and function
- promote the proliferative phase of menstrual cycle
- stimulate production of watery cervical mucus and activity of fimbriae and uterine tube cilia
- promote oogensis and ovulation
- during pregnancy, stimulate growth of uterus and enlargement of external genitalia and mammary glands
- metabolic effects
- neutral effects
- promotion of secondary sex characteristics
Define progesterone
Progesterone is a hormone that plays an important role in the menstrual cycle, pregnancy, and embryogenesis of humans and other species
Define estrogen
Estrogen is a group of hormones that play an important role in the sexual and reproductive development in women.
Estrogen is responsible for developing female sexual characteristics, including breast development, growth of pubic and underarm hair, and the start of menstrual cycles.
Estrogen is produced by the ovaries, adrenal glands, and fat tissues
True or false: Men do not have estrogen
False - they do have estrogen but in smaller amounts.
Testis migration during development
10-15 weeks
- Pelvic position
- Suspensory ligament
lengthens and
regresses
25-28 weeks
- Migrates over pubic
bone
- Reaches scrotum by
35-40 weeks
identify and describe the 2 functional compartments of the testis
The intratubular compartment:
- seminiferous tubules
- lined with complex stratified
germinal epithelium
- contains sperm cells and sertoli cells
- Sperm production
The peritubular:
- neuronal and vascular elements
- connective tissue, immune cells,
interstitial Leydig cells
- Steroid (androgen) production
Function of testis
Sperm and steroid hormone production
Leydig cells
(interstitial cells) =
steroidogenic
(cf theca cells in females)
-synthesize and secrete androgens (testicular hormones).
Summary of events in Spermatogenesis
- Mitotis
- produces large numbers of cells - Meiosis
- generates genetic diversity and ½
chromosomes - Spermiogenesis (Cytodifferentation)
- packages the chromosomes for effective
delivery to the oocyte
Hormonal regulation of testis by HPG
- The hypothalamus releases GnRH,
which reaches the anterior pituitary
via the hypophyseal portal veins. - GnRH causes anterior pituitary
gonadotropic cells to release FSH
and LH. - FSH indirectly stimulates
spermatogenesis by causing
Sertoli cells to release ABP, which
keeps the local concentration of
testosterone high.
ABP = androgen binding protein - LH stimulates Leydig cells to
secrete testosterone, which is
essential for spermatogenesis. - Testosterone acts at other body
sites [e.g., to stimulate maturation
of sex organs, development and
maintenance of secondary sex
characteristics, and libido (sex drive)]. - Negative feedback by testosterone
inhibits FSH and LH release from the
anterior pituitary and GnRH release
from the hypothalamus.
7 Inhibin released by Sertoli cells
feeds back on the anterior pituitary,
decreasing FSH release.
Interstitial Leydig cells
- Large, polygonal
*Lipid droplets
*Elaborate smooth ER
-Testosterone synthesis from
cholesterol - Differentiate to secrete testosterone in
early fetus
*Essential for development of male gonads - Period of inactivity (from about 5 months),
activated at puberty by gonadotropins
Actions of testosterone on reproductive organs
- stimulates formation of male reproductive ducts, glands, external genitilia
- promotes descent of testes
- stimulates growth and maturation of internal and external genitilia at puberty
- promotes long bone growth
promotes growth of larynx - enhances sebum and hair growth
- anabolic
- libido in males - promotes aggressiveness
Functions of the oviduct/Fallopian tube
- Capture of the newly ovulated oocyte
infundibulum - Transport of sperm and
oocyte(s) to the site of
fertilisation - Oviductal factors facilitate
fertilisation ampulla - Storage and capacitation of sperm
isthmus - Supports early embryonic development
ampulla & isthmus - Transport of the early embryo to the uterus
isthmus - Embryo modulates the oviductal
environment
Sperm maturation and movement in the male reproductive tract
- Maturation in epididymis
*DNA stabilisation
*Chromatin condensation
*Concentration - Storage also in vas deferens
before ejaculation in seminal
fluid (= semen)
Accessory glands
Seminal vesicles
* 70-75% of volume
* Alkaline fluid, fructose-rich
* Energy/muscular
contractions in female tract
Prostate
* 20-25% of volume
* Enhances sperm motility
* Proteases to fluidize the
ejaculate
* Antimicrobials
Bulbourethral glands
* Mucous secretion
(preseminal fluid)
* Lubricates end of penis
(glans penis)
Role of the oviduct in sperm transport and maturation
- Formation of a holding
reservoir in the isthmus - Binds ejaculated sperm to
the epithelium - Allows sperm to complete
capacitation - Precisely times sperm
transport with the arrival of
a mature oocyte in the
ampulla
Capacitation: preparing the sperm for action
Process required before sperm can fertilise the oocyte
- Stripping of non-covalently bound epididymal/seminal
glycoproteins and sterols (e.g. cholesterol)
- Sperm plasma membrane stability – allows release of
enzymes from acrosome
- Hyperactivation and increased motility
- Female reproductive tract ideal for capacitation
- Proteolytic enzymes,
sterol-binding albumin
- High ionic strength
Summary of preimplantation development
- zygote
- 4-cell stage
- morula
- early blastocyst
- mature blastocyst
Two different types of the contraceptive pill:
- The combined oral contraceptive pill (COC)
contains estrogen and progestin - The progestin only pill (POP)
How does the pill work?
High plasma
estrogen
* Inhibits secretion of FSH
(and to a lesser extent, LH)
via -ve feedback (hypo & pit)
* Inhibits follicle maturation &
ovulation
High plasma
progestin
* Inhibits synthesis of LH
(via -ve feedback to the
hypothalamus & pituitary)
* Prevents LH surge
required for ovulation
High estrogen
Very fluid
Enhances sperm
penetration into
uterus
Thick
Prevents sperm
penetration into
uterus
High progesterone
Thickens cervical mucus
* Forms a mucus ‘plug’
around the cervix
* Prevents sperm gaining
access to the uterus
Why choose to take the progestin only pill over
the combined pill?
Women who have contraindications to
taking estrogen:
* History of hypertension
* History of stroke
* History of thromboembolism (DVT)
Problems with progestin only pill
* Irregular vaginal bleeding
* Potentially higher contraceptive failure rate
Common side effects of the COC pill
➢ tender breasts
➢ nausea and bloating
➢ headache
➢ weight gain/water retention
➢ less interest in sex
➢ brown patches on the face - melasma
➢ mood changes
➢ spotting
rare side effects of the COC pill
➢ increased risk of rare blood clots (more likely if
>35 years and smoke)
➢ increased risk of stroke
➢ increased risk of cancer (breast, cervical)
➢ migraines
➢ dizziness
➢ increased BP
Other hormonal contraceptive methods
- Injection (e.g. Depo-Provera)
- Vaginal ring (e.g. NuvaRing)
- Implant (e.g. Implanon NXT)
- Hormonal IUD (e.g. Mirena, Kyleena)
Infertility – What are the common causes in females
- Endocrine abnormalities
- Hypothalamic dysfunction
Weight/strenuous exercise/stress/travel - Pituitary disease
Hypothyroidism/hyperprolactinemia - Ovarian dysfunction
- PCOS, premature ovarian failure, abnormal follicle development
- Implantation abnormalities
- Luteal phase deficiency, ↓ progesterone production
- Delayed maturation of endometrium
Reproductive:
- Disrupted cycles and ovulations
oligomenorrhea/amenorrhea
- Arrested follicle maturation
- Polycystic ovaries
Endocrine:
- Hyperandrogenism
- acne, hirsutism
- LH hypersecretion
Metabolic:
- Obesity
- Insulin resistance
- Increased risk of type 2 diabetes and cardiovascular disease
Infertility – What are the common causes in males
- 2nd most common factor (after woman’s age)
- Varicocele – dilatation of Pampiniform plexus
- Reduced semen quality ( temp)
- Vas deferens blockage
- Retrograde ejaculation – problem with ejaculation reflex
- Hypogonadotropic hypogonadism (Kallman Syndrome)
Other risk factors for infertility
Overweight or obese
Oocyte quality
Sperm quality
* Stress
Sperm production
Ovulation/cycles
* Smoking
Sperm count/quality
Oocyte quality
* Alcohol
Sperm count/quality
Impacts on ovarian reserve
Disrupted cycles
Hormones in ART
- Required for controlled ovarian hyperstimulation
- Maximise number of follicles ovulating per cycle (1 → many)
- Exogenous gonadotropins:
- Injection of FSH daily for growth of follicles to large antral stage
(monitored by ultrasound); aim for 22-35; <9 = low responder - Injection of LH to induce resumption of meiosis in oocyte (maturation)
and ovulation (typically 36-40 h post-LH) - GnRH agonist – given continuously prior to and during
gonadotropins to suppress natural ovulation - Progesterone also given for luteal support after embryo transfer
What can go wrong with fertility treatments?
- Ovarian hyper-stimulation syndrome (OHSS)
- Due to hormone treatments for oocyte pickup
- Women with PCOS are susceptible
- Mild, moderate, severe, critical (can be fatal)
- Multiple birth rate (relatively low in Australia due to SET) * Preterm delivery
- Low birth weight babies
- No pregnancy or miscarriage (~20% result in live birth)
- Costly, emotionally draining, and painful for oocyte donor
Progestin
synthetic form of progesterone
COC
The combined oral contraceptive pill
contains estrogen and progestin
POP
The progestin only pill
ART
(Assisted Reproductive Technology)
Generally involve surgically removing eggs, combining them with sperm in the laboratory, and returning them to the woman’s body or donating them to another woman
Most common types of ART:
1. IVF
2. ICSI
This definition does not include:
- Treatments involving only sperm (e.g. artificial insemination, IUI)*
- Treatments to stimulate egg production/ovulation without subsequent retrieval.
IVF
In Vitro Fertilisation
- 2-3 day cleavage stage transfer or 5-6 day blastocyst transfer
General procedure:
Aim for ~8 viable embryos; transfer to mother (usually 1-2) or cryopreserve.
Issue: Often excess viable embryos
ICSI
IntraCytoplasmic Sperm Injection
- single sperm injected
- increasingly common
- used when male infertility measured (motility/sperm count)
PCOS
Polycystic ovary syndrome
* Most common endocrine disorder of women in their reproductive years.
* Has a prevalence of 6-15% worldwide, causing major economic burden.
* Is a complex, heterogeneous disorder with reproductive, endocrine and metabolic features.
* Aetiology of PCOS is unknown and there is no cure.
Two different types of the contraceptive pill:
- The combined oral contraceptive pill (COC) contains estrogen and progestin
- The progestin only pill (POP)
Why choose to take the progestin only pill over the combined pill?
Women who have contraindications to
taking estrogen:
* History of hypertension
* History of stroke
* History of thromboembolism
Problems with progestin only pill
- Irregular vaginal bleeding
- Potentially higher contraceptive failure rate
Clinical features of PCOS
Reproductive:
- Disrupted cycles and ovulations - oligomenorrhea/amenorrhea
- Arrested follicle maturation - Polycystic ovaries
Endocrine:
- Hyperandrogenism - acne, hirsutism
- LH hypersecretion
Metabolic:
- Obesity
- Insulin resistance
- Increased risk of type 2 diabetes and cardiovascular disease
Female anatomic abnormalities
- Tubal disease
Inflammatory scarring (STIs, pelvic inflammatory disease), septic abortion, surgery, IUD, salpingitis - Tubal blockage
- Endometriosis
- Uterine fibroids/polyps/septum
Endometriosis
- Abnormal growth of endometrial tissue outside the uterus in pelvic cavity
- Responds in normal way to hormones → pain and fibrosis
- Affects ovaries, fallopian tubes and uterus
- Can block movement of sperm and egg/embryo in tubes
Female fertility tests
- blood test and ultra sound
- X-ray
3.ovarian reserve
Male fertility tests
- semen analysis (sperm count, motility, morphology, consistency of seminal fluid)
- DNA fragmentation test
- Sperm aggultination
LH
Luteinizing hormone (LH) is a hormone produced by the pituitary gland that plays an important role in sexual development and functioning
In women, LH is required to stimulate the ovarian follicles in the ovary to produce the female sex hormone.
In men, LH causes the testes to make testosterone.
FSH
Follicle-stimulating hormone (FSH) produced by the anterior pituitary gland in response to gonadotropin-releasing hormone (GnRH) from the hypothalamus.
In males, FSH stimulates Sertoli cell proliferation, which is the most significant contributor to testicular volume in children.
In females, during the follicular phase of the menstrual cycle, FSH stimulates the maturation of ovarian follicles.
Andorgens
Androgens are a group of hormones that contribute to growth and reproduction in both males and females.
Androgens are synthesized from cholesterol and are produced primarily in the gonads (testicles and ovaries) and also in the adrenal glands
In females, androgens play an important role in sexual development, libido, and bone health
Gonadotropin
Gonadotropins are a group of hormones that regulate ovarian and testicular function and are essential for normal growth, sexual development, and reproduction
The human gonadotropins include 1. follicle-stimulating hormone (FSH)
2. luteinizing hormone (LH)
3. human chorionic gonadotropin (hCG)
Granulosa cells
Granulosa cells are a type of cell in your ovaries that produce hormones including estrogen and progesterone.
GnRH
gonadotropin-releasing hormone
controls pituitary gonadotropins
produced in the hypothalamus and released in response to circulating levels of estrogens and progesterone
HPG
The hypothalamic-pituitary-gonadal (HPG)
a complex endocrine system that regulates normal growth, sexual development, and reproductive function.
Major androgen in males
Testosterone
Major androgen in females
DHEA
Capacitation: preparing the sperm for action
- Process required before sperm can fertilise the oocyte
- Stripping of non-covalently bound epididymal/seminal glycoproteins and sterols (e.g. cholesterol)
- Sperm plasma membrane stability – allows release of enzymes from acrosome
- Hyperactivation and increased motility
- Female reproductive tract ideal for capacitation
- Proteolyticenzymes, sterol-binding albumin
- High ionic strength
Blocks to polyspermy
- Oocyte membrane block:
- oocyte sperm-binding receptors shed
- Cortical reaction:
- sperm into oocyte triggers Ca2+ surge from intracellular stores in ER
- cortical granules fuse to oocyte plasma membrane and undergo exocytosis
- ZP hardens and destroys sperm- binding receptors (zona reaction)
Fertilisation
- Meiotic division completed:
- ovum and 2nd polar body formed - Formation of male and female pronuclei
- DNA in each pronucleus
replicates, pronuclei move
together and mitotic spindle forms - nuclear envelopes dissolve, releasing chromosomes - Maternal and paternal chromosomes combine, forming diploid zygote. = Fertilization
Sertoli cells
support the developing sperm
‘nurse cells’
(also called sustentocytes) extend from basal lamina to tubule lumen and surround developing spermatogonium and all other stages
- Maintains blood-testis-barrier
- Provides nutrients from blood
- Move developing sperm towards the lumen
- Secrete testicular fluid for sperm transport
- Phagocytosis
- Produce androgen-binding protein
(ABP) – concentrates T - Produce inhibin - -ve feedback to inhibit FSH release
Compare oogenesis and spermatogenesis
Time to produce one gamete:
Oo = 13-50 years
spermo= 74 days
occurrence during lifetime
spermo= puberty to old age
oo= begins in fetal life ends menopause
number of gametes per meiotic division
spermo= 4 equal size
oo = 1 large ovum 2-3 polar bodies
number of gametes per lifetime
spermo= >1 trillion
oo = <500
error rate
spermo = 5%
oo = 20%
Cells surrounding developing gametes
spermo - one sustentocyte
oo= many granulosa cells
Spermiogenesis = cytodifferentiation
- One spermatid develops into one spermatozoan
- Shape change: round → elongated
- Formation of tail: motility
- Midpiece: mitochondria for energy
- Superfluous cytoplasm shed into tubule
- Acrosome formation: modified lysosome structure
‘enzymatic knife’
Structure of human spermatozoan
Head:
- Condensed nucleus
- Acrosome: contains enzymes important
for fertilisation
Midpiece:
- Metabolic region containing coiled mitochondria
- Provides energy (ATP) for motility
Tail (flagellum):
- Fibrous sheath around continuous axonemal core
