How to make a baby, or year 1 HLC in an hour

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

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

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 – 2ooocyte • 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 zonapellucida 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.Thus, 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 disc @ 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

24. notochord formation • The notochord forms at the primitive node from invaginatingepiblast 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 (extraembryoniccoelom)

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 • 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 (intraembryoniccoelom) • 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 intraembryoniccoelom 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 • Extraembryoniccoelom 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: • 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