1. Embryology II
2008

2. Cleavage
Zygote
Blastomeres
Morula
Blastocyst

3. Blastocyst Trophoblast – outer cell mass Embryoblast – inner cell mass
Blastocyst cavity – from ED 4
ED5 - loss of zona pellucida – “hatching” - possibility of implantation
Cells of trophoblast express adhesive molecules – adhesion to the epithelial lining of uterus (secretory phase of menstrual cycle)

5. Implantation
Adhesion to the endometrium – embryonic pole Trophoblast – proliferation and cell coalescence – syncytium
Cytotrophoblast – proliferating cells
Syncytiotrophoblast – loss of inter-cellular borders
Implantation – proteolytic enzymes (metalloproteinases) – cytotrophoblast
Syncytiotrophoblast – penetrates among epithelial cells = it pull embryo in the endometrium

6. Implantation

7. Implantation

8. Implantation ED 9 – blastocyst is implanted in mucosa
It is covered by the coagulation plug
Syncytiotrophoblast develops in contact places with maternal tissue, successively surrounds whole blastocyst
Maternal reaction on embryo – decidual reaction – secretion of mucus, glycogen accumulation and oedema
Decidua basalis, marginalis, capsularis and parietalis

10. Immune reaction Endometrium – immunologically favored tissue
Progesterone – decreases nonspecific immune reaction – (complement)
Secretion of Interleukin-2 – decreases specific reaction
Syncytiotrophoblast and cytotrophoblast does not express common antigens – or they are covered - both form barrier between maternal and fetal tissues
Cytotrophoblast shell – cells of cytotrophoblast penetrate stem villi and form barrier between maternal and fetal connective tissues

11. Ectopic implantation
Abdominal cavity (Douglas pouch – retro-uterine cavity), ovary (primary ovarian pregnancy), uterine tube (95%) - most frequent in ampulla, intestitiale – in uterine horn
Placenta previa
Placenta accreta, percreta – penetrates into the zona basalis and myometrium

12. Prenatal losses Implantation tests embryos
Chromosomal abnormalities are the most frequent causes of spontaneous abortion
Immune reason - auto-antibodies
More that 50% embryos are unable to implant
Only 25 – 30% zygotes survive to birth

13. Development of embryoblast
Inner cell mass differentiates in two layers even before implantation - epiblast and hypoblast
Epiblast – columnar cells
Hypoblast – cubic cells

14. Amnion
Amniotic cavity (ED8) – appears among cells of epiblast – differentiation into amnioblasts and columnar cells of epiblast
Cavity is small, later surrounds whole embryo

15. Hypoblast
Cell proliferation and migration along the cytotrophoblast - (squamous epithelium) lining of blastocyst cavity – exocoelomic Heuser´s membrane
Blastocyst cavity is also called exocoelomic cavity or primary yolk sac
Extraembryonic reticulum (extracellular matrix) is produced between Heuser´s membrane and cytotrophoblast

16. ED12 – cells – extraembryonic mesoderm (probably from epiblast)
Exocoelomic vesicles – they fuse in new chorionic cavity – extraembryonic coelom – between yolk sac and cytotrophoblast
Cavity growth separates amnion and yolk sac from chorion – junction – connecting stalk
Mesoderm – visceral and parietal layers

18. Yolk sac
ED12 - hypoblast proliferates again – cells migrate along Heuser´s membrane – secondary definitive yolk sac (smaller than primary)
Primary yolk sac – exocoelomic vesicules - disappears
Function
Haematopoesis and development of vessels – vitellinne vasculature (blood islands)
Production of serum proteins, metabolism of nutrients
Germ cells

19. Embryonic nutrition
Resource in embryo – for first 4 – 8 blastomers, only
Nutrition – diffusion from fluid in uterine tube and uterus
Growth (proliferation) needs effective transport of gases (oxygen and carbon dioxide) and metabolites into the cells – development of vessels and placenta
Development of chorionic villi, cardiovascular system, contact with maternal blood

20. Development of chorion - placenta
Development of lacunae in trophoblast (ED9)
Contact with maternal vessels – blood into the lacunae – intervillous spaces
Vascular system needs adaptation for pregnancy – development of utero-placental vessels from spirale arteries (under influence of hormones) – otherwise IUGR develops
Implantation is regulated by hormones – takes place in the lamina functionalis, only

22. Development of chorion
Chorion frondosum, chorion laeve
Primary stem villi – syncytiotrophoblast and cytotrophoblast (ED 11 to 13)
Secondary stem villi – syncytiotrophoblast, cytotrophoblast, extraembryonic mesoderm (ED16)
Terciary stem villi (definitive) – syncytiotrophoblast, cytotrophoblast, extraembryonic mesoderm and vessels (ED21)

23. Function of trophoblast
Transport of respiratory gases
Transport of metabolites and electrolytes
Transport of maternal antibodies (IgG)
Production of hormones: progesteron, estriol, hCG, somatomammotropin (placental lactogen)

25. Development of embryoblast - gastrulation
Development of 3 germ layers: ectoderm, mesoderm and endoderm
Proliferation – formation of primitive knot and primitive streak
Loos of intercellular junctions
Bottle cells
Cell migration

26. Formation of embryonic axis
Antero-posterior
Embryonic – vegetative pole

27. Embryonic axes Antero-posterior Left-right Dorso-ventral
Cells are determinated for different structures of the body
Fate map

28. Basic morphogenetic processes
Proliferation
Apoptosis
Association – cells express intercellular junctions
Migration – loss of intercellular contacts – cells express adhesive molecules for attachment to the intercellular matrix
Induction → determination and differenciation

29. Regulatory genes
Transcription factors – specific – in certain types of cells or stages of development (promoter or enhancer) genes beginning developmental cascade or network – signal transduction pathway - basic helix-loop-helix or zinc finger
Signaling molecules – growth factors
Receptors for signaling molecules are also needed

30. Cascade of regulatory genes
Maternal effect genes – antero- posterior axis, germ cells
Zygotic:
Segmentation genes – gap, pair-rule, segment-polarity genes
Homeotic (Hox)

32. Homeodomain proteins Hox genes – in clusters
Cranio-caudal segmentation of the body
Genes are activated and expressed according to a strictly sequence
Pax genes – development of CNS, senses and epithelial cells
Sox genes
Other – Lim

34. Signaling molecules – cytokines, growth factors
TGF-β, FGF, BMP4
Hedgehog, Wnt (wingless)
Chordin, noggin, follistatin, activin, lefty
Cell surface receptors
Receptor kinases (tyrozin, serin-threonin)
Notch – lateral inhibition - prevent cells from differentiation into the same cell type - neurons

35. Signaling molecules
Retinoid acid (vitamine A) binding to CRABP (cellular retinol-binding protein) – transcription factor
Function – regulation of hox genes, cell differenciation (epithelial cells, blood cells)
Vitamine A is strong teratogene.