Suzie Rayner
Human Life Cycle 1 – Is sex necessary? [Largely
covered in Endo]

Describe the cardiovascular events associated with the erection of the penis.
Pudendal artery supplies blood to the penis.
Dorsal vein removes blood from the penis.
Erection occurs from increased blood flow to the corpora cavernosa. This is stimulates by
parasympathetic nervous system which induces dilation of pudendal artery.
Outflow of blood is stopped by compression of the dorsal vein due to increase in pressure
in corpora cavernosa.
[Urethra is protected by corpus spongiosum which is less turgid]

List the neural control mechanisms involved in penile erection, indicating
which one is the most important
Most important is parasympathetic nervous system as increased parasympathetic
action to the smooth muscle of the pudendal artery induces dilation → increased blood
flow in corpora cavernosa.
[Parasympathetic nervous system counteracts the sympathetic maintained myogenic
tone.]
Afferent pathway:
Tactile stimulus → afferent fibres in pudendal nerve → spinal cord
Efferent pathway:
Suzie Rayner
3 possible:
Nervous System
Nerve
Erection?
Parasympathetic
Pelvic
Promotes
Somatic
Pudendal
Promotes
Sympathetic
Hypogastric
Depresses
Penis: Flaccidity → Tumescence → Erection
Mechanism of smooth muscle dilatation
[Release of acetylcholine stimulates NO synthase → NO gets converted to cGMP which
causes dilatation of arterial smooth muscle.]
Clitoris is the erectile tissue in women, increases in size with increased blood flow.
Mechanism is likely to be due to release of NO.


Define the various stages of the menstrual cycle
Understand the changes that occur in the endometrium during the different
stages of the menstrual cycle
Suzie Rayner
Menstrual Phase:

4-5 days

Cycle begins on first day of menstruation

Shed blood and endothelium

Flow of 20-80ml
Proliferation Phase [N.B. everything becomes more]:

9 days

Growth of follicles occurs, controlled by 17β-oestradiol from follicles

2-3x increase in thickness of endothelium

[phase of repair and proliferation – epithelium repairs, glands increase in
number]
Secretory Phase:

13 days

Controlled by progesterone (luteal phase of ovarian cycle) and oestrogen (but
less so)

Formation, functioning and growth of corpus luteum

Glands in epithelium become wider and tortuous [due to progesterone]

Thicker endometrium [due to progesterone and oestrogen]

Spiral arteries


Know how the different stages of the ovarian cycle relate to the stages of the
menstrual cycle
Describe the various stages and events of the ovarian cycle and the hormones
acting at these various stages
Follicular phase and luteal phase of the ovarian cycle are linked by chemicals produced
during these phases, which changes in endometrium.
Follicular phase produces 17β-oestradiol → growth of follicle
Luteal phase produces progesterone → widening of glands and thickening of
endometrium

Know which hormones act at various stages of the menstrual and ovarian cycle
Suzie Rayner


Explain why the changes occurring in the endometrium are important for
implantation
Describe how the endometrium is maintained if pregnancy ensues
Corpus Luteum is maintained by human chorionic gonadotrophin (hCG), which is
produced by the syncytiotrophoblast.
Therefore progesterone and oestrogen continue to be produced.

Describe the endometrial changes if pregnancy does not occur
No fertilization

Corpus luteum regresses

Menstrual phase occurs
Suzie Rayner

Understand that the menstrual cycle various in its length from female to female
and also within one female from month to month

Describe other methods of how the sperm and egg can be artificially brought
together
In vitro fertilisation
Human Life Cycle 2 – In the beginning…
Summary of early development:
1st Trimester:
Weeks 1-2: Blastocyst stage
Weeks 3-8: Embryonic stage
Week 9 onwards: Fetal stage
2nd Trimester:
Rapid Growth of Fetus
3rd Trimester:
Fat production
Fertilisation:

Occurs in the fallopian tube, at the distal end (ampulla)

Sperm penetrates the several oocyte coats

Zona pellucida prevents polyspermy and permits implantation at correct site

Fertilisation causes oocyte to complete meiosis II – completes number of
chromosomes, determines gender
Post-fertilisation:

Zygote travels down fallopian tubes

Divides – first cleavage at around 20 hours → Morula (12-16 cells) →
blastocyst

Zona pellucida is shed

Implantation, hCG production.
Suzie Rayner

Why do we study development?
o Know how structures develop
o How normality arises/how abnormality arises
o Positioning of adult structures
o Understand that several tissues form at same time, requiring same genes

What structures are required for development of the human to ensue?
Female and male germ cells. [Spermatozoon, Oocyte]

Define and understand the following terms:
Gametes: mature germ cells [male – spermatozoa, female – oocytes]
Fertilisation: the process in which the nucleus of a spermatozoon enters the oocyte and
fuses with the female pronucleus to produce a zygote.
Pronuclei: nucleus of mature germ cells, haploid
Zona pellucida: clear, acellular membrane that surrounds the oocyte protecting against
polyspermy (multiple sperms entering)
Haploid: 23 chromosomes in the cell, 22 autosomes and 1 sex chromosome.
Diploid: 46 chromosomes in the cell, pairs of autosomes and a pair of sex chromosomes.
Implantation: process in which the blastocyst imbeds in the endometrium.
Suzie Rayner
First cleavage division: first cytoplasmic division by meiosis, cell membrane infolds as
a deep furrow, dividing cell into 2.
Formation of morula: the zygote when it has 12-16 cells (just before it becomes a
blastocyst)
Formation of blastocyst: hollow ball of blastomeres, formed when fluid is pumped into
morula after its compaction.
Inner Cell Mass: a.k.a embryoblast. Contains blastomeres which form embryo.
Trophoblast: Outside region of blastocyst which invades the endometrium, forms the
placenta.
Embryo: tissues arising from the zygote which later contribute to fetus/child.


Comprehend that development does not always go to plan and that
abnormalities can arise at different levels.
Give examples of chromosomal abnormalities that may occur
Mosaicism, Structural, Numerical
Down’s syndrome (trisomy 21)
Turner’s syndrome (45, X)
Kleinefelter’s syndrome (47, XXY)
Patau’s syndrome (Trisomy 13)
Edward’s syndrome (Trisomy 18)

Name possible sites where an ectopic pregnancy may arise.
Most common in the fallopian tubes (95%)
Other locations:

Ovary

Peritoneal cavity
Suzie Rayner

Name the two layers that the inner cell mass differentiates into to give rise to
the bilaminar disk stage of development and how the two layers give rise to the
third body or germ layer of the embryo.
Inner cell mass differentiates into 2 layers:

Epiblast – forms amniotic cavity and fluid

Hypoblast – forms yolk sac
Day 15:
Gastrulation: formation of trilaminar embryo

Coordinated process of cell movement.

Has organiser at top and bottom end of embryonic ectoderm – Cranial and
Caudal
Suzie Rayner

Primitive streak from caudal end – where cells from epiblast are proliferating
and moving into gap between epiblast and hypoblast.
This results in formation of 3 layers:

Epiblast becomes ectoderm.

The mesoderm forms between the two layers

Hypoblast becomes endoderm.


Primitive streak moves towards cranial end from caudal end
Primitive node forms
Human Life Cycle 3 – Pattern Formation

Name the structures that are derived from the three body or germ layers of the
embryo.
Ectoderm: develops into skin and nervous system
Mesoderm: develops into skeleton, muscle, kidney, heart, blood
Endoderm: develops into gut, liver and lungs

Day 17:
Define how the neuroectoderm gives rise to the neural plate and how this
structure folds to form an early neural tube that will give rise to the brain and
spinal cord later in development.
Suzie Rayner
Notochord:

forms at primitive node from invaginating epiblast cells

extends cranially, forming basis of axial skeleton

involved in inducing formation of neural tube and somite formation
Neurulation - Day 19-27:



Notochord induces ectoderm to become
neuroectoderm.
Neuroectoderm gives rise to:
o Neural plate
o Neural groove
o Neural folds
Ultimately gives rise to neural tube
Neural Crest:

arises from crest of neural folds

migrates from neurectoderm into underlying
mesoderm [see following diagram]

gives rise to:
o melanocytes (melanin production)
o Glial and Schwann cells
o cranial nerves
o odontoblasts (creation of dentin – tooth
enamel)
o connective tissue and bones of face and
skull
Suzie Rayner

Define the divisions of the intra-embryonic mesoderm and briefly describe
which structures each will give rise to.
Intra-embryonic mesoderm is divided into:

Paraxial mesoderm: becomes somites

Intermediate mesoderm: becomes urogenital

Lateral plate mesoderm: lines body cavities and surround organs (coelom) –
splits into two (visceral next to endoderm, parietal next to ectoderm)
Suzie Rayner
Somites [3 layers]:

Sclerotome – precursor to cartilage and bone

Myotome – precursor to muscle

Dermatome – precursor to skin
1st – Day 20
Anterior to posterior, 35 by Day 30.
Parts of extra-embryonic mesoderm will become:

Body stalk – umbilical cord

Amnion, yolk sac, chorion

Describe which two parts of the embryonic disk always remain as a bilaminar
disk and the consequences of this.
Buccopharangeal membrane at front of embryo and cloacal membrane at bottom.
These mark where the gut starts and finishes.


Which part of the neural tube develops most vigorously during early
development and what is the consequence of this?
Give an example of genetic regulation of embryonic development.
Example:
Hox genes:

Establish A-P axis (anterior-posterior?)

Differences in vertebrae

CNS divisions

Patterns of limbs
One signal that controls activation of Hox genes is Retanoic Acid (derivative of Vit. A)
Suzie Rayner

Define the causes of abnormalities during embryonic patterning.
All Chromosomal
Genetic examples:

Holt-Oram syndrome (heart/hand defects)

Achondroplasia (dwarfism)

Cleft lip

CF
Environmental:

Dietary

Alcohol abuse

Drug use

Radiation

Rubella
Spina Bifida (posterior neuropore doesn’t close properly, neural tissue bulges out)
Suzie Rayner
Summary of embryonic development (first 9 weeks)
Time
Day 6
Day 8-9
Day 12-13
Week 3
Week 4
Week 5
Week 6
Week 7
Week 8
Event
Attachment to endometrial epithelium
Implantation and formation of trophoblast
shell
Bilaminar embryonic disc
Trophoblast invasion and contact with
maternal blood
Formation of trilaminar disc
Formation of CNS
Formation of somites
Blood vessel initiation
Heart forms
Formation of placental villi
Closure of neural tube
Face and arm initiated
Umbilical cord forms
Elaboration of placental villi
Face and Limbs continue
Face, ears, hands, feet, liver, bladder, gut,
pancreas
Face, ears, fingers, toes
Lungs, liver, Kidneys
Placental elaboration continues
Villous Localisation
Placental endocrinology becomes dominant
Size
2mm
3mm
4mm
5-8mm
10-14mm
17-22mm
28-30mm
[N.B. up to Week 5, Week approximately equals Length]
HLC 4 – Body Cavities
Placental mammals evolved from egg-laying reptiles, therefore same cavities but newly
evolved roles:
Cavity/structure
Yolk sac
Chorionic cavity
Chorion
Amniotic cavity
Allantois
Allantoic mesoderm
Role
Part in gut development, other than that redundant
Obliterated early
Gives rise to placenta
Embryo floats in it, later tests its urinary and respiratory
systems into it
Gives rise to part of urinary bladder
Gives rise to placental blood vessels
Suzie Rayner
Chorion and amnion
eventually fuse (chorioamnion) and obliterate
chorionic cavity.
[N.B. Amniocentesis – used to check for embryo abnormalities, culture embryonic cells
and test for α-fetoprotein as indicative of neural tube defect]

Explain how the intra-embryonic coelom develops


Cavities form in preoral and lateral plate mesoderm.
These join to form a horseshoe shape called intra-embryonic coelom
The intra-embryonic coelom
develops into:
Pericardial cavity (cranially –
heart)
Pleural cavity (intermediate –
lungs)
Peritoneal cavity (caudally –
urogenital)
Suzie Rayner

Explain how the cranial part of the intra-embryonic coelom forms the
pericardial cavity
Head and tail folding:

Tucks developing heart and pericardial sac ventrally

Pinches gut tube off yolk sac

Narrows body stalk
Completion of head folding:

Forebrain now cranial to heart

Gut tube connected to yolk sac by narrow stalk

Heart ventral to gut tube

Original cranial part of coelom is now ventral to intermediate parts


Describe the process of development of the visceral and parietal pericardium
Explain the derivation of the visceral and parietal peritoneum
Develop from lateral plate mesoderm – splits in two:


Visceral adjacent to endoderm
Parietal adjacent to ectoderm

Give an account of lateral folding of the embryo
Lateral body folding:

Embryo’s body is turned into cylinder from sheet.

Rolls up gut tube, nips off yolk sac

Cuts intraembryonic coelom off from chorionic cavity

Amniotic cavity surrounds embryo except at body stalk

Be able to give an account of formation of the body cavities and how the lateral
plate mesoderm is so important in their development
Suzie Rayner
Human Life Cycle 5 –
The placenta: life support system of the fetus

Draw simple sketches to show the differentiation of the chorion through morula
and blastocyst stages
In blastocyst:

Inner cell mass develops into embryo, amnion and yolk sac

Trophoblast (epithelial layer of the chorion) forms a fused layer
(syncytiotrophoblast), which eventually develops into the placenta

Define cytotrophoblast and syncytiotrophoblast
Cytotrophoblast: inner layer of the trophoblast, consisting of cells which contribute to
the amnion and the syncytiotrophoblast.
Syncytiotrophoblast: outer layer of the trophoblast, consists of a syncytium of giant
cells and invades endothelium forming placenta
[Syncytium: many nuclei in same extent of cytoplasm]

Describe the invasion of maternal tissues by the syncytiotrophoblast during
and after implantation
Suzie Rayner

Syncytiotrophoblast burrows
through the uterine
epithelium to implant the
conceptus within the uterus
wall
[Resembles Cancer]




invades uterine epithelium
and connective tissue
invades and destroys small
vessels of uterus lining
(causing maternal blood to
flow into intervillous space)
Widens uterine arteries
(increasing flow)
Sheds fragments into
maternal blood
These fragments may metastasise to
mothers lungs or may reach systemic circulation
This causes pre-eclampsia:

Increased blood pressure

Protein leaking into urine

Caused by metastasis of syncytiotrophoblast causing vascular disturbance or
insufficient placental invasion of uterine wall

Compare the main sources of nutrition of the embryo or fetus before
implantation, during the first trimester and in the latter two trimesters
Before implantation:

Embryo depends on its own reserves and fluid in the uterine tube

No net. growth

Expansion of blastocyst depends on the uptake of NaCl and water.
Week 2 – Week 8/12:

Maternal tissue fluid and breakdown products within intervillous space
Week 8/12 onwards:

Maternal blood flow through intervillous space

Explain the terms “ectopic pregnancy” “placenta praevia” and indicate why
these conditions are dangerous
Suzie Rayner
Ectopic pregnancy: where the conceptus has implanted in the wrong place
Placenta praevia: when the placenta is sited so that it will block normal cervical delivery
Cause complications in labour, cause ruptures to mothers reproductive system…etc

Explain why the term “haemochorial” is applied to the human placenta
There is no point where the fetal and maternal blood come into direct contact.

Explain the origin of the intervillous spaces and the establishment of maternal
blood circulation through them
Chorionic villi are initially sprouts of the trophoblasts over the whole surface, but over
time they:

retreat to basal side forming placental disc

branch and acquire cores of connective tissue

become vascularised and connected to embryos cardiovascular system
Allantoic vessels grow through the body stalk to the placenta, allowing all exchanges
with the mother.
Syncytiotrophoblast adapts blood flow (see previous learning objective)
Feto-maternal blood
interface:
Fetal blood circulates
through villous cores
in capillaries
Maternal blood flows
from dilated arteries
directly into
intervillous space
Suzie Rayner

Define “decidualisation” and explain its importance
Decidualisation: normal response of endometrium to implantation

modifies uterine arteries to ensure adequate blood flow

provides protective mechanisms against rejection of feto-placental tissue by
mothers immune system

Describe the origin of the amnion and outline the origins and importance of
amniotic fluid
Inner cell mass divides forming epiblast. Within the epiblast layer, many small fluidfilled spaces appear which combine forming the amniotic cavity.
Amnion lines the chorion and contains amniotic fluid which the fetus floats it, drinks and
excretes into. (acts as a shock absorber)

Sketch the tissue layers separating maternal from fetal blood

Contrast the mechanisms by which (a) respiratory gases (b) electrolytes,
glucose and amino acids and (c) immunoglobulin G cross the materno-fetal
barrier

Lipid soluble molecules are unrestricted (e.g. blood gases, ethanol, anaestetics,
steroids)
Small uncharged molecules are unrestricted (e.g. water, urea)
Large hydrophilic molecules are limited by membrane transporters (e.g.
glucose, amino acids)
Proteins are held back unless there is a specialised transport system (e.g. for
IgG)



[N.B. Respiratory gases – unrestricted, electrolytes etc – limited, IgG – specialised
transport]
Suzie Rayner


Indicate the endocrine roles of the placenta
Suggest how the placenta may avoid attack by the maternal immune system
Secretes hormones which:

maintain pregnancy

promote lactation (prepare breasts for it)

suppress menstruation

Involved in initiation of labour

Does not evoke maternal response to foreign tissue

Outline how uterine blood loss is minimised when the placenta is delivered

Know what proportion of the maternal cardiac output perfuses the uterus at
term
1/6 of maternal blood.
Human Life Cycle 6 –
The significance of the Y chromosome




Explain the significance of the Y chromosome with particular reference to the
SRY gene.
Describe the role of the SRY protein with respect to control over gonadal
development.
Gonads derived from somatic mesenchymal tissues (forming matrix) and
primitive germ cells (forming gametes)
Differentiation of gonads begins after Week 6 – formation of testes is actively
initiated (i.e. without activation, become female)
Within developing seminiferous cords (in males):

Primordial germ cells → spermatozoa

Mesodermal cells → Sertoli cells of seminiferous tubules

Between seminiferous tubules, clusters of interstitial cells condense → Leydig
cells
SRY (sex determining region) gene is located on the Y chromosome

SRY initiates formation of sertoli cells (expressed in male sertoli cells)
SRY protein is a transcription factor regulating other gene activity.
Suzie Rayner

Draw a diagram illustrating the effects of androgens and Mullerian Inhibitory
Factor on fetal reproductive system development.

Draw a diagram illustrating the development of Testicular Feminization
Syndrome (Complete androgen insensitivity syndrome – CAIS)

Draw a diagram illustrating the consequences of excess androgens in a fetal
female genotype.
Excess androgens cause both male and female internal genitalia to develop, and male
external genitalia.
Suzie Rayner
Human Life Cycle 7 –
Development of urinary and reproductive organs

Outline the development of the kidneys, ureters, urinary bladder and urethra.
Intermediate mesoderm gives rise to most of upper urinary and genital systems
Intermediate mesoderm gives rise to urogenital ridge, within which the nephrogenic
cord develops (kidney making).
Nephrogenic cord is source of most of urogenital system (exceptions: primordial germ
cells, lower urinary tract, perineum)
Development of kidneys:

Sweeps cranio-caudially (top to bottom)
Region
Cervical
Thoraco-lumbar
Mesonephric duct
Sacral mesonephros
Ureter grows out from mesonephric duct.
Event in kidney development
Never differentiates, regresses by Week 4
Mesonephros differentiates, but has mainly
gone by Week 8
Persists in males
Appears in Week 5, becomes definitive
kidney
Suzie Rayner
Maldevelopment of kidneys:


fail to reposition (retain sacropelvic position)
joined together – trapped below inferior mesenteric artery (horseshoe kidney)
Development of urinary bladder:
Allantois gives rise to most of bladder
[N.B. slender duct extending to umbilicus normally closes but if it does not it can cause
problems]
Cloaca becomes partitioned into urogenital sinus and rectal sinus.
[N.B. sometimes partitioning is incomplete and congenital fistula (opening) connects
urogenital and alimentary tracts]
Maldevelopment of ureters:



Complete duplication
Partial duplication (become one at some point)
Ectopic (opening in abnormal place)
Position of kidneys and ureters:
Shared sections of ureter and mesonephric duct (in males) are absorbed into the back of
the bladder.
Ureters now open into bladder and the Mesonephric ducts into urethra.
Differential growth shifts metanephric kidneys from sacral site of origin to the posterior
wall of upper abdomen (up and backwards)
Suzie Rayner


Outline the mechanism of differentiation of male and female structures in the
pelvis and perineum, including gonads, uterine tubes, uterus, vagina, vulva,
ducti deferentes, seminal vesicles, prostate, scrotum and penis.
Outline gonadal descent and the formation of the inguinal canal.
In males – (the relationship of the gonads and the mesonephric duct.)

Gonads develop medially to mesonephros kidney

Most of mesonephros atrophies but parts between gonads and mesonephric
ducts persists

These persistent parts will become efferent ducts between testis and ductus
deferens

Developing testes link with mesonephric duct through some persistent
mesonephric tubules



In 4th month testes descend into scrotum (through inguinal canal)
Ductus deferens develop into seminal vesicles
Urethra develops into prostate
In Females – (Paramesonephric ducts)

Paramesonephric ducts develop in most lateral part of intermediate mesoderm

In females they become uterine tubes, uterus and upper vagina

[Not important in males]


From Week 8 - 4th month, paramesonephric ducts link with each other and the
urogenital sinus to assemble definitive female structure
Ovaries descend from origin, in upper lumbar region, to the pelvis
Primordial germ cells

give rise to eggs and sperm

arise from yolk sac

in week 6 they migrate to genital ridge (via hindgut and mesentery)

A few survive to form PGCs and somatic cells of next generation
Suzie Rayner
Sex determination – covered in HLC 5
Development of external genitalia:

Same for both genders from weeks 3-6
Female:
Genital swelling →
labia majora
Cloacal fold → urethral
fold → labia minora
Urethra opens into
vestibule posterior to
clitoris
Suzie Rayner
Male:
Expansion of phallus
Fusion of urethral folds to enclose the penile
urethra (if incomplete – hypospadius)
Expansion and fusion of genital swellings to
form scrotum

Outline the origin of the disorders of urogenital system development below
Duplication of a ureter
from mesonephric duct
Absence of kidneys
Pelvic and horseshoe kidneys
Pelvic – kidneys do not migrate from their origin
Horseshoe – kidneys are joined together and get stuck below the inferior mesenteric
artery
Polycystic kidneys
Wilm’s tumour of the kidney
Hypospadias
Incomplete fusing of the urethral folds
Mismatch between genetic and phenotypic sex (pseudohermaphroditism)
Androgen insensitivity (receptors don’t work)