How to make a baby,
or year 1 HLC in an hour
Mark Chamberlain
21/5/09
how and why have sex?
The key reason for sex is for the human species to procreate
This requires
•Intercourse or IVF
•Fertilisation
•Reproductive system
MALE
FEMALE
GONADS
Testes
Ovaries
INTERNAL
DUCTS
Efferent ducts
Epididymis
Vas
Seminal vesicles
Urethra
Fallopian tubes
Uterus
Vagina
EXTERNAL
GENITALIA
Penis
Scrotum
Vulva
testis
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housed in the scrotum
spermatic cord leads to back of bladder, where it joins with seminal vesicles
and leads into the ejaculatory duct, which opens into the prostatic urethra
Consists of
• seminiferous tubules - sperm production
• Sertoli cells - maturation process
• Leydig cells - production of testosterone
ovaries
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cortex - contains follicles with oocytes
medulla - vascular area
no duct system
Contains developing follicles at varied stages
At ovulation secondary oocyte (Graafian or vesicular follicle) (stopped in
metaphase II) ruptures through ovarian wall, ovulated into pelvic cavity and
is picked up by fimbrae of fallopian tubes and transported to uterus
penile stimulation and erection
Tactile stimulation → afferent fibres of pudendal nerve → spinal cord
Thoughts from limbic system → efferent fibres → penis
• parasympathetic via pelvic promotes
• somatic via pudendal promotes
• somatic via hypogastric suppresses
Involves change from flaccidity → tumescence → erection
Caused by ↑ parasympathetic activity to smooth muscle of pudendal artery,
causing release of NO, stimulating ↑ cGMP to induce dilatation, leading to ↑
blood flow into the corpus cavernosum
This counteracts the sympathetic-maintained myogenic tone
Outflow of blood ↓ by compression of dorsal vein following ↑ in pressure
Urethra protected from increased pressure by surrounding corpus spongiosum
menstrual cycle
Endometrium consists of 3 layers
• stratum compactum
• stratum spongiosum
• stratum basale (basal layer)
Cyclical events (~28 days) of menstruation and ovulation
throughout a woman’s reproductive life
UNLESS fertilization of a released ovum by a mature
spermatozoon occurs
USUALLY, this occurs following copulation (coitus)
between man and woman
BUT in vitro fertilization a reality
ovulation
GnRH acts on anterior pituitary to cause release of:
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FSH – stimulates maturation of follicle
LH – stimulates ovulation at day 14 (leading to oocyte completing Meiosis I,
stopping in Meiosis II at metaphase)
Male germ cell = spermatozoa
Female germ cell – 2o oocyte
Meiosis - haploid chromosome #
Fertilisation - diploid chromosome #
Maternal and paternal chromosomes are the blueprint for new individual
fertilisation
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Takes place in fallopian tubes at the
distal end of the ampulla
Sperm capacitation needed before
Sperm binds to the ZP3 receptor
Sperm penetrates the several egg coats
using the acrosome reaction
Cortical reaction prevents multiple
sperm entry
Fertilisation causes oocyte to complete
Meiosis II; restores diploid number of
chromosomes; determines sex
post fertilisation
Takes 9 months (40wks) for a human baby to develop
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1st Trimester - most important as this is when body forms:
• Weeks 1-2 Blastocyst stage
• Weeks 3-8 Embryonic stage (Organogenetic period)
• Weeks 9-onwards Fetal stage
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2nd Trimester - rapid growth of fetus
3rd Trimester - fat production
- zygote travels down fallopian tube
- first division at approximately 30h
- sheds zona pellucida and implants
- hCG production initially from corpus luteum
Days 1-6
twins
ectopic pregnancy
developmental abnormalities
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Can arise at different levels:
• Chromosone
• Genetic
• (Environment)
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Chromosomal and genetic effects account for majority of losses of
pregnancies or abnormalities in first few weeks – which often go
unrecognised
May be numerical or structural. 50% of conceptions end in abortion - 50% of
these due to chromosomal abnormality.T hus, 25% of conceptuses have a
chromosomal defect.
Chromosomal abnormalities account for 7% of major birth defects.
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Downs syndrome(trisomy 21)
Turner syndrome (45, X0)
Patau Syndrome (trisomy 13)
cri-du-chat (chr 5 partial loss)
developmental abnormalities
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Genetic accounts for 8% of major birth defects
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vascular formation (lethal),
holoprosencephaly (lethal)
cleft lip
Polydactyly
Environmental influences have a major impact/influence on patterning and
growth events in later development, less so on very early development
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lack of Folic acid in diet
alcohol abuse
drug use
Radiation
viruses eg: Rubella
teratogens
implantation
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Contact between maternal and fetal systems is dynamic
Invasion of syncytiotrophoblast then cytotrophoblast causes vascular
remodelling and the fetomaternal interface
Point of contact is the placental villi and the placental spiral arteries
Day 9 - invasion
Day 13 – lacunae formation
bilaminar disc @ day 9
gastrulation
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First stage of folding starts with gastrulation
Primitive streak forms, setting up antero-posterior axis
germ layer formation
germ layers
Germ layer
organs
ectoderm
Skin, nervous
system
Mesoderm
Skeleton, muscle,
kidney, heart,
blood
endoderm
Gut, liver, lungs
notochord formation
The notochord forms at the primitive node from invaginating epiblast cells, from
around day 17, and extends cranially - forms the basis of the axial skeleton.
-The notochord is involved in inducing the neural tube and somite formation
neurolation
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Ectoderm is induced via notochord/mesoderm to become neuroectoderm
Neuroectoderm gives rise to neural plate, neural groove and folds and
ultimately to the neural tube
Failure of this process leads to spina bifida
Neurulation begins around day 19, and ends by day 27 with closure of
posterior neuropore.
body cavities
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Cavities form in the preoral and lateral
plate mesoderm
these join to form a horseshoe-shaped
space called the (intraembryonic) coelom.
The coelom will develop into:
• Pericardial cavity (cranially)
• Pleural cavities (intermediate)
• Peritoneal cavity (caudally)
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The caudal ends open into the chorionic
cavity (extraembryonic coelom)
neural crest
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arise from crest of the neural folds
migrates from neuroectoderm into underlying mesoderm
give rise to a whole host of tissues including:
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connective tissue and bones of face & skull
melanocytes
glial cells and schwann cells
cranial nerves
odontoblasts
somatogenesis
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form on either side of neural tube
from paraxial mesoderm
made up of 3 parts:
• sclerotome - cartilage/tendon/vertebral
column
• myotome - muscle precursors
• dermatome - skin precursors
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first somite appears day 20
form anterior to posterior as the axis
of embryo elongates
by day 30 there will be 35 somites
mesoderm
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Intraembryonic
• Paraxial mesoderm – somites
• Intermediate mesoderm – urogenital
• Lateral plate mesoderm - line body cavities and surround the organs
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Extraembyonic
• Body stalk - umbilical cord
• Amnion, yolk sac, chorion
Lateral folding
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Axis elongates
Lateral plate mesoderm develops a cavity (intraembryonic coelom)
splits into two mesoderm layers
• parietal (adjacent to ectoderm) lines body cavities and forms body wall
• Visceral (adjacent to endoderm) forms gut wall
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Turns the embryo’s body into a cylinder instead of a sheet
Rolls up the gut tube and nips it off from the yolk sac
Cuts the intraembryonic coelom off from the chorionic cavity
Means that the amniotic cavity surrounds the embryo except at the body stalk
Head and tail
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developing heart and pericardial sac (cranial
coelom) tuck in ventrally
gut tube pinches off from the yolk sac and
narrows the body stalk
Completion of the head-fold:
• Forebrain now cranial to heart
• Gut tube connected to yolk sac by a narrow
stalk
• Heart ventral to gut tube
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Originally cranial part of coelom now ventral
to intermediate parts (pericardial sac ventral
to pleural sacs)
Genetic regulation of development
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All of the processes discussed are controlled by signals from genes. Complex
gene interactions occur throughout development to form a normal fetus.
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Example: Hox genes:
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establish A-P axis,
differences in the vertebrae,
CNS divisions,
pattern the limbs.
One of the signals that control the activation of Hox genes is Retinoic acid, a
derivative of Vitamin A.
Developmental milestones
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1st Trimester
• Wks1-2 Blastocyst stage – cell division/implantation
• Wks 3-8 Embryonic stage – patterning and formation of
organs/tissues
• Wks 9- Fetal stage - growth
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2nd Trimester
• Massive growth and development of fetus and maturation of internal organs.
• Placental growth.
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3rd Trimester
• Fat deposition
• Movements
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all patterning, organogenesis etc complete by 3 months; then ‘just’ growth of
fetus
Fetus in utero
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Higher vertebrates produce amniote eggs
Complex system of cavities servicing the developing
embryo
Well wrapped up in membranes
Floating in its own pond of amniotic fluid
• Extraembryonic coelom develops from spaces in the
trophoblast
• Yolk sac – rudimentary apart from role in gut
development
• Chorion – gives rise to placenta
• Chorionic cavity – obliterated early
• Amniotic cavity – embryo floats in it, later tests its
urinary and respiratory systems into it
• Allantois – gives rise to part of urinary bladder
• Allantoic mesoderm – gives rise to placental blood
vessels
Chorion and amnion eventually fuse, creating a chorioamnion and obliterating the chorionic cavity
Amniocentesis may be used to test for fetal plasma
protein (α-fetoprotein) in amniotic fluid –
placenta
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A disc of fetal tissue
Interface between maternal and fetal vascular systems
Transporter
Anchor
Biosynthetic factory
Immunological conundrum
exchange
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Products in:
• Glucose, amino acids, lipids, oxygen
• Peptides and proteins
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Products (waste) out:
• Carbon dioxide
• Metabolites
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Diffusion
• Concentration gradient
• Facilitated diffusion
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Active transport
Receptor-mediated
Aqueous or lipid-specific
immunoregulation
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Normally exposure of tissue to foreign antigens activates the immune
response, leading to rejection within a few days or weeks.
In pregnancy there is intimate contact between maternal and fetal tissues,
with no evidence of any rejection
separation
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Maternal blood and fetal blood never mix
Pregnancy MAY be independent of the uterus - e.g. ectopic pregnancy
biosynthesis
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Hormones (pregnancy specific or general)
Growth factors for placental development
Cytokines to regulate feto-maternal interface
Intermediate mesoderm
Gives rise to most of the upper urinary and genital systems
• Gives rise to Urogenital Ridge
• Within which develops the nephrogenic cord
• Source of most of UG system (except Primordial Germ Cells, lower urinary tract and
perineum)
Kidney differentiation
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sweeps cranio-caudally
Cervical part (pronephros) never
completes differentiation and
regresses by wk 4
Thoraco-lumbar mesonephros
differentiates but has mainly gone by
wk 8
Mesonephric duct persists in male
Sacral metanephros appears in wk 5
and becomes definitive kidney
Ureter grows out from mesonephric
duct
Urinary bladder
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The allantois is a hindgut outgrowth into the body stalk – gives rise to most
of the bladder
• The duct extending to the umbilicus normally closes but may persist and cause
problems
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The cloaca becomes partitioned into the urogenital sinus and the rectal sinus
• Sometimes this is incomplete and a congenital fistula connects the urogenital and
the alimentary tubes
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The shared sections of the ureters and the mesonephric ducts (in the male)
are absorbed into the back of the bladder
The ureters now open into the bladder, the mesonephric ducts into the
urethra
Differential growth shifts the metanephric kidneys from their sacral site of
origin to the posterior wall of the upper abdomen
urinary maldevelopment
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Quite often a ureter may be completely or partially duplicated
Less commonly a second ureter may be ectopic opening into the vagina,
urethra or other organs instead of the bladder
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One kidney may fail to reposition properly and so retains a sacro-pelvic
position = pelvic kidney
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If the kidneys are joined together, their ascent is prevented because they are
trapped below the inferior mesenteric artery = a horseshoe kidney
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The urogenital sinus and rectal sinus become separated by the uro-rectal
septum
At this stage the cloacal membrane still persists so that the urogenital and
anal openings are closed.
These subsequently open but may cause serious problems for the newborn
child if this fails to happen
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The gonads develop medially to the mesonephric kidneys
Most of each mesonephros atrophies but the parts between the gonads and
the mesonephric ducts persist
These persistent mesonephric tubules will become the efferent ducts that
connect the testis to the ductus deferens
paramesonephric ducts
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The paramesonephric (formerly
called Mullerian) ducts develop in
the most lateral part of the
intermediate mesoderm in both
sexes
In males they play no important
part in development
In females they become the
uterine tubes, uterus and upper
vagina
primordial germ cells
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PGCs are the cells that give rise to the eggs and sperms - the “germ line” is
an expression describing this continuity of germ cells from generation to
generation
They arise from the yolk sac and in week 6 migrate via the hindgut and its
mesentery to the genital ridges medial to the mesonephros
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PGCs colonise the gonads:
• They are the only cells that can become eggs or sperms
• They are the only cells that can undergo meiotic (= reduction) division to form
haploid cells
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Unlike the somatic cells, a few of them survive to form the somatic tissues
and PGCs of the next generation
gonadal development
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In both sexes, the gonads are derived from
• Somatic mesenchymal tissues forming matrix
• Primitive germ cells forming gametes
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Gonads “indifferent” up to 6th week in utero
Y chromosome then actively initiates formation of testes
Otherwise undifferentiated gonads develop into ovaries
the SRY gene
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Located on Y chromosome
expressed in male Sertoli cells
sry gene initiates formation of Sertoli cells
sry gene expression
• synthesis of a transcription protein - the SRY protein
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transcription factor regulating other gene activities
other genes clearly involved in early gonadal development and sex
determination
SRY protein
expression of Y
chromosome
(SRY gene)
expression of
X chromosome
OVARIES
TESTES
Leydig
cells
Mullerian
Inhibitory Hormone
Mullerian (paramesonephric) Ducts
Sertoli
cells
Female internal genitalia
ANDROGENS
External
genitalia
Wolffian (mesonephric) Ducts
Male internal genitalia
MALE
FEMALE
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The gonads develop medially to the mesonephric kidneys
Most of each mesonephros atrophies but the parts between the gonads and
the mesonephric ducts persist
These persistent mesonephric tubules will become the efferent ducts that
connect the testis to the ductus deferens
Developing testes link up with the mesonephric duct though some persistent
mesonephric tubules
Mesonephric duct develops into the ductus deferens that will carry sperm to the
male urethra
Paramesonephric duct undergoes no further development
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During the 4th month the testes descend through the inguinal canal towards
their final site in the scrotum
Remember that the male genital duct system develops from the
mesonephric duct and persisting mesonephric tubules
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The accessory male genital glands (seminal vesicles and prostate) develop
from buds from the lower end of the ductus deferens and from the urethra
respectively
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Between week 8 and the 4th month the paramesonephric ducts link with
each other and with the urogenital sinus to assemble the definitive female
system
The ovaries descend from their original upper lumbar location to the pelvis
development of the external genitalia
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Between the 3rd and 6th weeks the external genitalia develop in the same
indifferent form in embryos of both sexes
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In the absence of androgens the indifferent form progressively develops into
the definitive female pattern
The urethral folds and genital swelling form the labia minor and majora
The urethra opens into the vestibule posterior to the clitoris
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Androgen stimulation in the male stimulates:
Expansion of the phallus
Fusion of the urethral folds to enclose the penile urethra – incomplete in
hypospadias
Expansion and fusion of the genital swellings to form the scrotum
any questions?