1. How to make a baby, or year 1 HLC in an hour
Mark Chamberlain
21/5/09

2. 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

3. testis 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

4. ovaries 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

5. 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
Female equivalent is clitoris

6. 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

7. ovulation GnRH acts on anterior pituitary to cause release of:
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

8. fertilisation
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

9. post fertilisation Takes 9 months (40wks) for a human baby to develop
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
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

10. Days 1-6

12. twins

13. ectopic pregnancy

14. developmental abnormalities
Can arise at different levels:
Chromosone
Genetic
(Environment)
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.
Downs syndrome(trisomy 21)
Turner syndrome (45, X0)
Patau Syndrome (trisomy 13)
cri-du-chat (chr 5 partial loss)

15. developmental abnormalities
Genetic accounts for 8% of major birth defects
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
lack of Folic acid in diet
alcohol abuse
drug use
Radiation
viruses eg: Rubella

16. teratogens

17. implantation 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

18. Day 9 - invasion

19. Day 13 – lacunae formation

20. bilaminar day 9

21. gastrulation First stage of folding starts with gastrulation
Primitive streak forms, setting up antero-posterior axis

22. germ layer formation

23. germ layers Germ layer organs ectoderm Skin, nervous system Mesoderm
Skeleton, muscle, kidney, heart, blood
endoderm
Gut, liver, lungs

24. 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

25. neurolation
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.

26. body cavities 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)
The caudal ends open into the chorionic cavity (extraembryonic coelom)

27. neural crest arise from crest of the neural folds
migrates from neuroectoderm into underlying mesoderm
give rise to a whole host of tissues including:
connective tissue and bones of face & skull
melanocytes
glial cells and schwann cells
cranial nerves
odontoblasts

28. somatogenesis
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
first somite appears day 20
form anterior to posterior as the axis of embryo elongates
by day 30 there will be 35 somites

29. mesoderm Intraembryonic Extraembyonic Paraxial mesoderm – somites
Intermediate mesoderm – urogenital
Lateral plate mesoderm - line body cavities and surround the organs
Extraembyonic
Body stalk - umbilical cord
Amnion, yolk sac, chorion

30. Lateral folding 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
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

31. Head and tail
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
Originally cranial part of coelom now ventral to intermediate parts (pericardial sac ventral to pleural sacs)

32. Genetic regulation of development
All of the processes discussed are controlled by signals from genes. Complex gene interactions occur throughout development to form a normal fetus.
Example: Hox genes:
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.

33. Developmental milestones
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
2nd Trimester
Massive growth and development of fetus and maturation of internal organs.
Placental growth.
3rd Trimester
Fat deposition
Movements
all patterning, organogenesis etc complete by 3 months; then ‘just’ growth of fetus

34. Fetus in utero 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 chorio-amnion and obliterating the chorionic cavity
Amniocentesis may be used to test for fetal plasma protein (α-fetoprotein) in amniotic fluid –

35. placenta A disc of fetal tissue
Interface between maternal and fetal vascular systems
Transporter
Anchor
Biosynthetic factory
Immunological conundrum

36. exchange Products in: Products (waste) out: Diffusion Active transport
Glucose, amino acids, lipids, oxygen
Peptides and proteins
Products (waste) out:
Carbon dioxide
Metabolites
Diffusion
Concentration gradient
Facilitated diffusion
Active transport
Receptor-mediated
Aqueous or lipid-specific

37. immunoregulation
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

38. separation Maternal blood and fetal blood never mix
Pregnancy MAY be independent of the uterus - e.g. ectopic pregnancy

39. biosynthesis Hormones (pregnancy specific or general)
Growth factors for placental development
Cytokines to regulate feto-maternal interface

40. 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)

41. Kidney differentiation
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

42. Urinary bladder
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
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

43. 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

44. urinary maldevelopment
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
One kidney may fail to reposition properly and so retains a sacro-pelvic position = pelvic kidney
If the kidneys are joined together, their ascent is prevented because they are trapped below the inferior mesenteric artery = a horseshoe kidney

45. 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

46. 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

47. paramesonephric ducts
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

48. primordial germ cells
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

49. 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
Unlike the somatic cells, a few of them survive to form the somatic tissues and PGCs of the next generation

50. gonadal development In both sexes, the gonads are derived from
Somatic mesenchymal tissues forming matrix
Primitive germ cells forming gametes
Gonads “indifferent” up to 6th week in utero
Y chromosome then actively initiates formation of testes
Otherwise undifferentiated gonads develop into ovaries

51. the SRY gene 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
transcription factor regulating other gene activities
other genes clearly involved in early gonadal development and sex determination

52. ADRENOGENITAL SYNDROME = EXCESS ANDROGENS IN GENETIC FEMALE FETUS
expression of
X chromosome
OVARIES
Mullerian (paramesonephric) Ducts
Female internal genitalia
External
genitalia
expression of Y chromosome
(SRY gene)
SRY protein
Sertoli
cells
Leydig
TESTES
Mullerian
Inhibitory Hormone
ANDROGENS
Wolffian (mesonephric) Ducts
MALE
Male internal genitalia
TESTICULAR FEMINIZATION = ANDROGEN NON-RESPONSIVENESS IN GENETIC MALE FETUS
ADRENOGENITAL SYNDROME = EXCESS ANDROGENS IN GENETIC FEMALE FETUS

53. 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

54. 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

55. 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

56. 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

57. 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

58. development of the external genitalia
Between the 3rd and 6th weeks the external genitalia develop in the same indifferent form in embryos of both sexes

59. 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

60. 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

61. any questions?