1. Embryology and congenital anomalies
Yasser Orief M.D.
Lecturer of Obstetrics & Gynecology, Alexandria University
Fellow, Lϋbeck University, Germany
DGOL, Auvergné University, France

2. Embryology – study of the origin and development of single individual
Prenatal period
Embryonic period – first 8 weeks
Fetal period – remaining 30 weeks

3. Embryonic Period

4. Fetal Period

5. The Basic Body Plan
Skin – dermis and epidermis
Outer body wall – trunk muscles, ribs, vertebrae
Body cavity and digestive tube (inner tube)
Kidneys and gonads – deep to body wall
Limbs

6. The Basic Body Plan

7. Week 1 – from zygote to blastocyst
The Embryonic Period
Week 1 – from zygote to blastocyst
Conception – in lateral third of uterine tube
Zygote (fertilized oocyte) moves toward the uterus
Blastomeres – daughter cells formed from zygote
Morula – solid cluster of 12–16 blastomeres
“Mulberry”
Blastocyst – fluid-filled structure – ~ 60 cells

8. The Embryonic Period Stages of first week Zygote 4-cell Morula
Early blastocyst
Late blastocyst (implants at this stage)

9. Fertilization and the Events of the First 6 Days of Development

10. Week 2 – The Two-Layered Embryo
Bilaminar embryonic disc – inner cell mass divided into two sheets
Epiblast and the hypoblast
Together they make up the bilaminar embryonic disc

11. Week 2 – The Two-Layered Embryo
Amniotic sac – formed by an extension of epiblast
Outer membrane forms the amnion
Inner membrane forms the amniotic sac cavity
Filled with amniotic fluid

12. Week 2 – The Two-Layered Embryo
Yolk sac – formed by an extension of hypoblast
Digestive tube forms from yolk sac
NOT a major source of nutrients for embryo
Tissues around yolk sac
Gives rise to earliest blood cells and blood vessels

13. Implantation of the Blastocyst

14. Implantation of the Blastocyst

15. Implantation of the Blastocyst

16. Week 3 – The Three-Layered Embryo
Primitive streak – raised groove on the dorsal surface of the epiblast
Gastrulation – a process of invagination of epiblast cells
Begins at the primitive streak
Forms the three primary germ layers

17. Week 3 – The Three-Layered Embryo
Three Germ Layers*
Endoderm – formed from migrating cells that replace the hypoblast
Mesoderm – formed between epiblast and endoderm
Ectoderm – formed from epiblast cells that stay on dorsal surface
*All layers derive from epiblast cells!

18. The Primitive Streak

19. Primitive node – a swelling at one end of primitive streak
The Notochord
Primitive node – a swelling at one end of primitive streak
Notochord forms from primitive node and endoderm
Notochord – defines body axis
Is the site of the future vertebral column
Appears on day 16

20. Formation of the Mesoderm and Notochord

21. Neurulation – ectoderm starts forming brain and spinal cord
Neural plate – ectoderm in the dorsal midline thickens
Neural groove – ectoderm folds inward

22. Neurulation (continued)
Neural tube – a hollow tube pinches off into the body
Cranial part of the neural tube becomes the brain
Maternal folic acid deficiency causes neural tube defects

23. Neurulation Neural crest Induction
Cells originate from ectodermal cells
Forms sensory nerve cells
Induction
Ability of one group of cells to influence developmental direction of other cells

24. The Mesoderm Begins to Differentiate
Somites – our first body segments
Paraxial mesoderm
Intermediate mesoderm – begins as a continuous strip of tissue just lateral to the paraxial mesoderm

25. The Mesoderm Begins to Differentiate
Lateral plate – most lateral part of the mesoderm
Coelom – becomes serous body cavities
Somatic mesoderm – apposed to the ectoderm
Splanchnic mesoderm – apposed to the endoderm

26. Changes in the Embryo

27. Changes in the Embryo

28. Week 4 – The Body Takes Shape
Folding of embryo laterally and at the head and tail
Embryonic disc bulges; growing faster than yolk sac
“Tadpole shape” by day 24 after conception
Primitive gut – encloses tubular part of the yolk sac
Site of future digestive tube and respiratory structures

29. Week 4 – The Body Takes Shape

30. Week 4 – The Body Takes Shape
Derivatives of the germ layers
Ectoderm forms
Brain, spinal cord, and epidermis
Endoderm forms
Inner epithelial lining of the gut tube
Respiratory tubes, digestive organs, and urinary bladder
Notochord – gives rise to nucleus pulposus within intervertebral discs

31. Week 4 – The Body Takes Shape
Mesoderm – forms
Muscle
Bone
Dermis
Connective tissues (all)
Mesoderm differentiates further and is more complex than the other two layers

32. Week 4 – The Body Takes Shape
Mesoderm (continued)
Somites divides into
Sclerotome
Dermatome
Myotome
Intermediate mesoderm forms
Kidneys and gonads

33. Week 4 – The Body Takes Shape
Mesoderm (continued)
Splanchnic mesoderm
Forms musculature, connective tissues, and serosa of the digestive and respiratory structures
Forms heart and most blood vessels
Somatic mesoderm – forms
Dermis of skin
Bones
Ligaments

34. Derivatives of Germ Layers

35. The Germ Layers in Week Four

36. Week 5-8 – The Second Month of Embryonic Development
Limb buds form
Embryo first looks recognizably human (week 8)
Head is disproportionately large
All major organs are in place

37. The Fetal Period
A time of maturation and rapid growth
Cells are differentiating during the first half of the fetal period
Normal births occur 38 weeks after conception
Premature birth is one that occurs before 38 weeks

38. Developmental Events of the Fetal Period

39. Developmental Events of the Fetal Period

40. Developmental Events of the Fetal Period

41. SEX DETIRMINATION

42. Sex determination
Sex determination in human is genetically controlled.
TDF (testis determining factor ) is a dominant gene on the Y chromosome.
Presence of this gene will lead to testicular formation.
In the absence of this gene the default sex is female.

43. The newly formed embryonic testis will secrete
Mullerian inhibitory factor (MIF) from Sertoli cells:
It causes regression of the mullerian ducts.
Regression of any germ cells that developed into oogonia.
Testosterone from the Leyding cells:
Differentiation and growth of the wollfian duct structures.
Masculinization of the external genitalia after conversion to DHT.

44. In the absence of signals from TDF:
sertoli cell differentiation does not occur.
Migrating germ cells differentiate as oogonia.
Interstitial cells differentiate as granulosa cells.
sex differentiation of germ cells is determined, not only by their genetic constitution, but also by their tissue environment.

45. In the absence of testosterone
In the absence of MIF :
Mullerian ducts differentiate and grow as female internal genitalia.
In the absence of testosterone
External genitalia are feminized.

46. PGCs on to ridge by week 6
First hint of gonad in week 4 but remain indifferent (or bipotential) until week 7. Only then can the type of gonad be distinguuished

48. So what does Y have to do with it in humans?

49. There is also a set of reproduction-specific (Rhox) homeobox genes expressed
In males one set in Sertoli cells, other set in Leydig cells
All genes are on the X chromosome
Are under androgen regulation
The Sertoli set is sequentially expressed and thought to provide mechanism by which Sertoli cells regulate germ cell devliopment (proliferate->devide-> differentiate)

50. From: Wolpert et al., Principles of Development

51. From: Gilbert, Developmental Biology

52. From: Gilbert, Developmental Biology

53. From: Wolpert et al., Principles of Development

54. From: Gilbert, Developmental Biology

55. From: Larsen, Human Embryology
Should take time to get familiar with other major defects seen in external genital system (e.g. uterine anomalies, cryptorchidism)
From: Larsen, Human Embryology

56. Type I
Agenesis uterine, or uterine hypoplasia
Type II
Uterus unicornuate
Type III
Uterus didelphys
Type IV
Uterus bicornuate (including arcuate uterus)
Type V
Uterus septate
Type VI
Uterine anomaly associated with DES exposure

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