Reproduction and Development Flashcards
Female: Mons pubis
secretion of pheromones (sexual attraction)
Female: Labia majora
role of protection and lubricating secretion
Female: Labia minora
rich in blood vessel, sensitive to stimulation
Female: Clitoris
very sensitive to sexual stimulation and can erect
Bartholin’s glands
secretion of thick fluid for lubrication during intercourse
Where does fertilisation take place?
Fallopian tubes
Where does the zygote move into?
Uterus
What are the two cell types found in the uterus?
- Germ cells (oocyte)
- Somatic cells
Ovarian functions
- Gametogenesis: oogenesis and folliculogenesis
- Steroidogenesis (production of hormones: oestrogens and progesterone)
Oogenesis
- Differentiation of the ovum into a cell competent to further develop when fertilised
- Occurs in the ovary
- Primary oocytes (primordial follicles): 1-2 million at birth, 300,000-400,000 at puberty, 10% released during the reproductive life (until menopause), apoptotic cell death
Process of oogenesis
- Oogonia divide by meiosis during embryonic development and stop
- Oocytes remain arrested until ovulation
- Meiosis is not completed until fertilisation
- Lifetime supply of developing eggs at birth
Which hormone stimulates follicular growth?
GnRH stimulates the pituitary gland to produce follicle stimulating hormone (FSH), the hormone responsible for starting follicle (egg) development and causing the level of estrogen, the primary female hormone, to rise
Which hormone causes ovulation?
Estrogen
Which cells of the follicle make oestrogen and progesterone?
Granulosa cells are the cellular source of estradiol and progesterone, the two most important ovarian steroids
What is the name of the follicle that is most mature?
The graafian, or mature, follicle may be up to 2.5 cm in diameter at the time of ovulation, and it protrudes from the surface of the ovary. An outer layer of theca cells and granulosa cells surround a vesicle containing fluid and the oocyte
What does the follicle become after ovulation?
The cells in the ovarian follicle that are left behind after ovulation undergo a transformation and become the so called corpus luteum and secrete progesterone
Folliculogenesis
Folliculogenesis is the developmental process of ovarian follicles starting from a reserve of quiescent primordial follicles set up in early life and ending with either ovulation or follicular death by atresia.
How long is the ovarian cycle?
27-29 days
What is ovulation
Ovulation is the process in which a mature egg is released from the ovary. After it’s released, the egg moves down the fallopian tube and stays there for 12 to 24 hours, where it can be fertilized
Follicular phase of the ovarian cycle
1-14th day,
the follicular phase is the stage of your menstrual cycle when your body is preparing to release an egg. This is a necessary process for pregnancy. Once the egg is released, the follicular phase is considered over
Luteal phase of the ovarian cycle
14-28th day, the luteal phase is the second half of your menstrual cycle. It starts after ovulation and ends with the first day of your period
Can pregnancy occur with low levels of LH?
If your LH levels are low, you may not be getting your period. Because LH triggers ovulation, low levels of LH can prevent ovulation, and thus pregnancy
High levels of LH
When the body’s levels of luteinizing hormone (LH) rise, it triggers the start of ovulation, and the most fertile period of the menstrual cycle occurs
What happens if FSH is low?
In women, a lack of follicle stimulating hormone leads to incomplete development at puberty and poor ovarian function (ovarian failure). In this situation ovarian follicles do not grow properly and do not release an egg, thus leading to infertility
FSH
In women, FSH helps manage the menstrual cycle and stimulates the ovaries to produce eggs.
High levels of FSH
If you are a woman, high FSH levels may mean you have: Primary ovarian insufficiency (POI), also known as premature ovarian failure
Steroidogenesis
All follicles are in competition with each other for FSH (Follicle-Stimulating Hormone).
In response to FSH, follicular cells synthesise oestrogen which feed back to the hypothalamus.
Only one or two leading follicles will form graafian follicles.
As negative feedback is exerted, the other developing follicles undergo atresia.
Once ovulation has occurred, the Graafian follicle turns into the corpus luteum and secretes progesterone.
What does progesterone maintain?
The uterine lining for embryo implantation
Gonadotropin hormones
Gonadotropin-releasing hormone causes the pituitary gland in the brain to make and secrete the hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In men, these hormones cause the testicles to make testosterone. In women, they cause the ovaries to make estrogen and progesterone
What happens to gonadotropin hormones during the luteal phase?
Gonadotropin secretion is strongly suppressed by progesterone and oestrogen = no further follicular growth
Fertilisation
Corpus luteum is maintained by a hormone secreted by the embryo after implantation (human Chorionic Gonadotropin: hCG)
No fertilisation (or failure of implantation)
Corpus luteum dies after approx. two weeks. Progesterone and oestrogen levels fall, anterior pituitary escapes from the negative feedback. Results in increase in gonadotrophin levels and the start of the follicular phase of the next cycle
- Follicular phase
Follicle stimulating hormone (FSH) is secreted from the anterior pituitary and stimulates growth of ovarian follicles
The dominant follicle produces estrogen, which inhibits FSH secretion (negative feedback) to prevent other follicles growing
Estrogen acts on the uterus to stimulate the thickening of the endometrial layer
- Ovulation
Midway through the cycle (~ day 12), estrogen stimulates the anterior pituitary to secrete hormones (positive feedback)
This positive feedback results in a large surge of luteinizing hormone (LH) and a lesser surge of FSH
LH causes the dominant follicle to rupture and release an egg (secondary oocyte) – this is called ovulation
- Luteal phase
The ruptured follicle develops into a slowly degenerating corpus luteum
The corpus luteum secretes high levels of progesterone, as well as lower levels of oestrogen
Estrogen and progesterone act on the uterus to thicken the endometrial lining (in preparation for pregnancy)
Estrogen and progesterone also inhibit secretion of FSH and LH, preventing any follicles from developing
- Menstruation
If fertilisation occurs, the developing embryo will implant in the endometrium and release hormones to sustain the corpus luteum
If fertilisation doesn’t occur, the corpus luteum eventually degenerates (forming a corpus albicans after ~ 2 weeks)
When the corpus luteum degenerates, estrogen and progesteron levels drop and the endometrium can no longer be maintained
The endometrial layer is sloughed away and eliminated from the body as menstrual blood (i.e. a woman’s period)
As estrogen and progesterone levels are too now low to inhibit the anterior pituitary, the cycle can now begin again
Where are the sperm produced?
Testes, seminiferous tubes
Cells involved in the testes
- Sertoli cells
- Leydig cells
Sertoli cells
aid in synthesis of sperm (nurse cells)
Leydig cells
produce testosterone
Testicular function
- Gametogenesis: spermatogenesis (spermatocytogenesis + spermiogenesis) differentiation of the spermatogonia into a sperm competent to move and fertilize
- Steroidogenesis (production of hormone: testosterone)
Spermatogenesis
- ‘Unlimited’ sperm supply: 200 to 300 million daily
- Optimal temperature is at 2C lower than core body temperature
- Duration = 74 days
- Decrease in sperm quality (after 35 y/o)
What can impact spermatogenesis and sperm quality?
Smoking increases DNA damage in sperm, marijuana decreases sperm production
What can impact spermatogenesis and sperm quality?
Smoking increases DNA damage in sperm, marijuana decreases sperm production
- Trauma and cancer
Spermacytogenesis
- Meiosis = from one diploid spermatocyte to four haploid spematids
- Occurs in the testis after puberty
Spermiogenesis
- Maturation of a round spermatid into a mature sperm
Four steps of spermiogenesis
- Golgi phase: intense golgi activity, mid-piece formation and DNA packaging (protamines)
- Cap phase: acrosome formation
- Tail phase: elongation of microtubules
- Maturation: removing residual cytoplasm and organelles by phagocytosis
Epididymis functions
- Storage:
- Sertoli cells secrete testicular fluid
- Sperm reach the epididymis (to be stored until ejaculation) - Sperm motility:
- Mature immotile sperm acquiring motility function
Inhibitin B
- Secreted by Sertoli cells
- FSH dependant
Testosterone
- Development of male reproductive tissues
- Secondary sexual characteristics at puberty: muscle and bone mass increase, growth of body hair and size of penis
- Secreted by Leydig cells
- LH dependant
What is meiosis?
Succession of two cell division:
- Separation of homologous chromosomes
- Separation of sister chromatids
Phases of meiosis
- Prophase
- Metaphase
- Anaphase
- Telophase
- Cytokinesis
Aims of meiosis:
- producing haploid gametes (cycle of life)
2. introducing genetic diversity
How is diversity implemented through meiosis
- Intra-chromosomal recombination: crossing over
- Inter-chromosomal recombination: assortment
- Random fertilisation
Chromosomes
Human diploid somatic cells have 23 pairs of chromosomes:
- 22 autosomal pairs and 1 sexual pair
- 46 chromosomes (23 paternal and 23 maternal)
What are two chromosomes in each pair called?
Homologous chromosomes or homologs
- Chromosomes in a homologous pair are the same length except the sexual pair XY
The result of mitosis
Two diploid cells (somatic cells, with no genetic variation = identical daughter cells)
The result of meiosis
Four haploid cells (with genetic diversity)
How is meiosis regulated in males?
In spermatogenesis, sperm cells do not form until the male has reached puberty. Each parent cell produces 4 sperm cells
How is meiosis regulated in females?
In oogenesis, only one oocyte is formed from the parent cell. The other 3 cells (called polar bodies) degenerate. The first meiotic division has taken place after the female is born. Maturation continues after puberty when an egg is released (end of meiosis I) and fertilised (end of meiosis II)
What is aneuploidy?
Aneuploidy means an organism does not have the normal number of chromosomes (failure in chromosome separation in meiosis)
Monosomic
If there is 1 less chromosome, this is referred to as monosomic, abbreviated as 2n - 1
Trisomic
If there is 1 extra chromosome, this is called trisomic, abbreviated as 2n + 1
Turner’s syndrome (X)
Ovaries defective or absent: sterile, no pubertal development - no menstrual cycle, rarely attain adult height of more than five feet
- Female
- 45 chromosomes
Triple X syndrome
Individuals have no sexual abnormalities, and may have children; some are mentally retarded
- Female
- 47 chromosomes
Klinefelter’s syndrome (XXY)
Internal and external genitals are male but testis are very small and do not produce sperm; underdeveloped pubic, facial and body hair, enlarged breasts; reduced sexual drive, tall and possible mental retardation
- Male
- 47 chromosomes
XYY syndrome
Individuals are tall (6ft and over) may show impulsive behaviour; sperm production often reduced (may be sterile)
- Male
- 47 chromosomes
Why is there no monosomic autosomal human individuals?
Pregnancies with an autosomal monosomy usually end in embryonic death
Why is the polar body generated?
The purpose of polar body formation is to conserve cytoplasm for the oocyte. If fertilized, the oocyte will develop into an egg cell, which will depend on components in the cytoplasm for its development. The polar bodies will get very little cytoplasm and will eventually degenerate.
Can sperm fertilise oocytes when they are newly ejaculated?
No
What is sperm capacitation?
Sperm capacitation refers to the physiological changes spermatozoa must undergo in order to have the ability to penetrate and fertilize an egg
How long does the process of capacitation take?
5-7 hours
Are capacitated sperm more active?
Yes
Location of sperm capacitation
Capacitation occurs in the uterus and oviducts and is facilitated by substances of the female genital tract
Aim of sperm capacitation
- To greatly increase the motility of the sperm flagellum
- To allow sperm capable of undergoing the acrosome reaction
How does capacitation modify the sperm?
- changes in glycoproteins, lipids, and ion channels in the plasma membrane
- lowering the resting potential of the plasma membrane (eg. become hyperpolarised)
- Unmasking of cell surface receptors to allow for binding to the zona pellucida (barrier covering the egg)
The acrosome reaction
The acrosome reaction culminates in fusion (and shedding) of the spermatozoal plasma membrane and outer acrosomal membrane, which allows acrosomal contents to be released and thus aid in penetration of the vestments of the oocyte and fusion with the oocyte’s plasma membrane
What is polyspermy?
The entrance of several spermatozoa into one egg
Prevention of polyspermy
To prevent polyspermy, the zona pellucida, a structure that surrounds mammalian eggs, becomes impermeable upon fertilization, preventing the entry of further sperm. The structural changes in the zona upon fertilization are driven by the exocytosis of cortical granules
What part of the sperm enters the cytoplasm of the oocyte?
Only the head, sperm plasma membrane remains behind
When does the second meiotic division take place?
Once the sperm has penetrated the oocyte, the secondary oocyte was previously arrested in metaphase of the 2nd meiotic division, and now forms the mature ovum and another polar body.
Fusion of pronuclei
- The male and female pronuclei are indistinguishable from one another
- The plasma membrane of the two pronuclei are dissolving and one diploid nucleus will remain
Name for a fertilised egg
Zygote
From where does the new zygote receive centrioles from?
Mitosis in the new zygote uses centrioles derived from the sperm. The oocyte has no centrioles
In what time frame is fertilisation completed by?
Within 24 hours of ovulation
Approx how may sperm reach the fertilisation site?
Only about 100 sperm reach the site; most degenerate and are absorbed by the female genital tract
How long can sperm survive within the female genital tract?
48 hours
What is triploidy?
Extra set of chromosomes , leads to early miscarriage
What is ART?
Assisted Reproductive Technology, in general, ART procedures involve surgically removing eggs from a woman’s ovaries, combining them with sperm in the laboratory, and returning them to the woman’s body or donating them to another woman
Who can access the ART treatment?
- couples who have been trying and failed to get pregnant for 1 year
- 1 out of 6 couples in the UK are subfertile
Causes of infertility in women:
- Hormone levels
- Ovulation
- Blocked tubes
- Damaged or absent ovaries
- Endometriosis
- Premature menopause
- Secondary amenorrhea
What is endometriosis?
Endometriosis is a condition where tissue similar to the lining of the womb starts to grow in other places, such as the ovaries and fallopian tubes
What is secondary amenorrhea?
Secondary amenorrhea refers to the absence of three or more periods in a row by someone who has had periods in the past. Pregnancy is the most common cause of secondary amenorrhea, although problems with hormones also can cause secondary amenorrhea
Causes of infertility in males:
- Low sperm count
- Low sperm motility
- No sperm
- Impotence including erectile dysfunction
- Aspermia
What is aspermia?
Aspermia is the complete lack of semen with ejaculation
Other factors that influence infertility
- Lifestyle = drinking, smoking, dietary pattern
- Environmental factors = exposure to plastic. ‘bisphenol A’
- Age
- Sexually transmitted disease (chlamydia and gonorrhea)
ICSI
IntraCytoplasmicSpermInjection
IUI
IntraUterineInsemination
Steps involved in embryo development
- Ovulation
- Fertilisation
- Cleavage
- Morula
- Early blastocyst
- Implantation
Hw are embryos graded?
Embryos and blastocysts are graded according to the UK’s National Excellence and Quality Assurance Scheme (NEQAS)
What are blastocysts?
Three days after fertilization, a normally developing embryo will contain about six to 10 cells. By the fifth or sixth day, the fertilized egg is known as a blastocyst — a rapidly dividing ball of cells. The inner group of cells will become the embryo. The outer group will become the cells that nourish and protect it
Blastocysts
- Inner cell mass (icm) forms the foetus
- Trophectoderm forms extra embryonic tissue
- Fluid filled cavity is called the blastocoel cavity
Hatching blastocysts
- Hatching occurs just prior to implantation
- Embryo breaks through the zona pellucida (ZP) due to proteases secreted by blastocyst
- Inability to hatch is reason for infertility; could be due to altered zona pellucida or to absence of essential protease for zona digestion
- Often assisted hatching is done in vitro during ART procedures
- In mutant mouse embryos lacking ZP1, the zona pellucida is weak and the embryos hatch prematurely
Implantation
- Occurs in the endometrium
- Window of implantation day 20-23
Has three phases:
- (Hatching)
- Apposition
- Adhesion
- Invasion
What is the role of Osteopontin in Implantation?
Just prior to ovulation, the endometrium begins to thicken and to expand in response to the release of estrogen from the ovaries. As the embryo moves through the fallopian tubes, the endometrium proliferates, changes in shape, becomes receptive to implantation, and produces a hospitable environment for the embryo
Why is hatching important at the blastocyst stage?
To adhere to the endometrial epithelium and implant
What are stem cells?
Stem cells are the body’s raw materials — cells from which all other cells with specialized functions are generated
Stem cell: cell cycle
Stem cells are characterized by two unique properties with respect to specialized cells; in vivo, they are able to divide by maintaining their stemness; this process is termed self-renewal. Additionally, all stem cells retain the capacity to progressively differentiate into mature cell types
Types of stem cells:
- Embryonic
- Adult (tissue) stem cells
- iOSCs = induced pluripotent stem cells
The inner cell mass
- Cells which go on to form the human
- Pluripotent stem cells
- Day 5-9 after fertilisation
- Can be collected and cultured
Totipotent
- Generate all types of body cells, germ cells and cells of the placenta
- First few divisions only
Pluripotent
- Generate all types of body cells
- Cells of the inner cell mass
Multipotent
- Generate limited cell types
- Tissue progenitors
Adult stem cells
- Also known as tissue stem cells
- Partially differentiated
- Limited potential for differentiation = multipotent
- Eg = blood cells
Types of adult stem cells:
- bone marrow
- peripheral blood (circulating)
- skin
- skeletal muscle
- liver
- brain
- adipose tissue
- heart
Tissue renewal
Tissue renewal determines the rate of cell division
- In many tissues, renewal derives from a limited number of stem cells
Tissue regeneration
The process of renewal and growth to repair or replace tissue that is damaged or suffers from disease
What are progenitor cells?
Progenitor cells are descendants of stem cells that then further differentiate to create specialized cell types
Animals that can go through tissue regeneration
- Sea hydra
- Planarian
- Fish
- Salamander
- Deadpool
Adult stem cells in research and clinics limitations
- Can be difficult to obtain
- Limited tissues
- Limited capacity for division
- limited cell numbers
What is cell dedifferentiation?
More specialised cells become less specialised
iPSCs
Reprogramming transcription factors
- Future approach = clinical personalised treatment
What are the two functions of Stem cells?
Self-renewal and differentiation
What are the 3 germ layers?
Ectoderm, Endoderm and Mesoderm
From where are derived the 3 germ layers and which embryo stage?
Derived from the ICM of the blastocyst
Which stem cells can be used in research?
Embryonic SCs, Adult SCs and iPSCs
What are the developmental periods of a baby?
- Germinal (0-2 wks)
- Embryonic (3-8wks)
- Foetal (9 wks - birth)
Germinal period
- Shortest developmental phase
- From zygote stage to fully implanted embryo
Germinal period wk - 1
Day 1 = fertilisation Day 2 = two cell stage Day 3 = morula Day 4 = early blastocyst Day 5 = Late blastocyst Day 6-7 = implantation
Germinal period wk - 2
Day 8 = bilaminar disc forms
Day 9 = trophoblast with lacunae
Day 10-11 = embryo in uterus 10-11 days after ovulation
Day 12 = extraembryonic mesoderm develops
Day 13= ulteroplacental circulation begins
Day 14 embryonic disc dorsal view
Embryonic period
- From implanted blastocyst to foetus
- Growth = cell division
- Morphogenesis = development shape, size or feature of particular organ or whole body
Differentiation = maturation of physiological process (eg. placenta)
Embryonic period wk - 3
Day 15 - laterality established
Day 16 - gastrulation: formation of germ layers
Day 17 - epiblast forms germ layers
Day 18 - trilaminar embryonic disc
Day 19 - CNS induction
Day 20 - neurulation: neural folds elevate
Day 21 - transverse section through somite region
What is gastrulation?
Gastrulation is defined as an early developmental process in which an embryo transforms from a one-dimensional layer of epithelial cells (blastula) and re-organizes into a multilayered and multidimensional structure called the gastrula
Gastrula ectoderm cells
- Outer surface = epidermal cells of the skin
- CNS = neuron
- Neural crest = pigment cell
Gastrula mesoderm cells
- Dorsal = notochrod
- Paraxial = bone tissue
- Intermediate = kidney/reproductive system
- Lateral = rbc, limbs and tissue around gut
Gastrula endoderm cells
- Digestive tube = stomach cells
- Pharynx = thyroid cells
- Respiratory tube = lung cells
Embryonic period wk - 4
Day 22 - neural tube closure begins Day 23 - neural tube zippers Day 24-15 - villus formation continues in the placenta Day 26 - pharyngeal arches present Day 27 - somite increase Day 28 - neurulation complete
What are somites
Somites determine the migration paths of neural crest cells and spinal nerve axons. Somites give rise to the cells that form the vertebrae
Embryonic wk - 5
Day 29 - arm and leg buds Day 30 - developing face Day 31 - gut development Day 32 - embryo in chorionic cavity Day 33 - umbilical ring Day 34 - optic cup and lens placode Day 35 - branchial arches and clefts
Embryonic wk - 6
Day 36 - physiological umbilical hernia Day 37 - developing face Day Day 38 - muscle development Day 39 - endodermal derivatives Day 40 - auricular hillocks Day 41 - atrial septum formed Day 42 - digit formation
Embryonic wk - 7
Day 43 - limb cartilages and digital rays
Day 44 - developing face
Day 45 - conotruncal and ventricular septa
Day 46 - sac development
Day 47 - external genitalia
Day 48 - facial prominences fused
Day 49 - digits present , eyelids forming
Fetal period
- 8th to 38th week of development (10th - 40th weeks of pregnancy / amenorrhea)
- From the 8th week foetus has human characteristics (limbs…) due to morphogenesis stage in the embryonic phase
- Maturation phase
When can abortions be carried out in England?
Before the 24th week of pregnancy (after, it can occur for medical reasons)
Why the 24th week?
After the 24th week, the foetus is viable outside the mother’s womb
When does the foetus settle into the cephalic position?
Around 33-36th week
What is cephalic position?
Foetus directed toward or situated on or in or near the head = head down position
Foetus at week: 9
Fetal stage begins
Foetus at week: 12
Sex organs differentiate
Foetus at week: 16
Fingers and toes develop
Foetus at week: 20
Hearing begins
Foetus at week: 24
Lungs begin to develop
Foetus at week: 28
Brain grows rapidly
Foetus at week: 32
Bones fully develop
Foetus at week: 36
Muscles fully develop
Foetus at week: 40
Full-term development
During what weeks are there the earliest reflexes linked to motion of arms and legs?
Week 9-12
What is teratogenesis?
The process by which congenital malformations are produced in an embryo or foetus
What is situs inversus (0.01%)
Situs inversus is a genetic condition in which the organs in the chest and abdomen are positioned in a mirror image from their normal positions