Seminar2012 mothter safe

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  • 다양한 장기의 기형의 critical period에 대해 그려놓은 유명한 그림이지요. 제 가 오늘 강의에서 말씀드리는 날짜는 선생님들이 씃ㅣ는 날짜와 2주 차이가 있습니다. 저는 배란부터 시간을 세므로 제가 2주라면 선생님들은 2주를 더해서 4주로 생각하시면 됩니다. 수정되고 8주까지를 embryonic period 라 하고 세포 한 개에서 사람이 만들어 지는 정말 dynamic한 시기입니다. 이후에는 크기가 주로 커지는 fetal pe제riod 이구요. 3주에서 9주 초 까지 major morphologic abnormality가 생기는 시기이고 3주에 CNS anomaly를 선두로 heart anomaly 등 줄줄이 생기게 되는 데요. 제가 준비한 내용은 크게 두 부분이구요. 앞부분에서는 간단히 수정에서 neurulation시기까지 살펴보고 뒤는 심장발생을 좀 자세히 다루는 것으로 마무리 하겠습니다.
  • 줄기세포의 특징
    반복적으로 분열하면서 스스로 재생산 (unlimited self-renewal)
    정상적인 다른 특정한 기능을 가진 세포로 분화(highly regulated differentiation)
    배아줄기세포는 inner cell mass를 이용
    발달과정과 같이 모든 신체기관으로 분화가 가능하기 때문에 다능성 줄기세포(pluripotent stem cell)라 부름
  • 자궁내막에 완전히 파묻혔어요.
  • Seminar2012 mothter safe

    1. 1. Human EmbryologyHuman Embryology 제일병원 병리과 전이경
    2. 2. Critical periods of development for various organ systems and the resultant malformations
    3. 3. First week of development: ovulation to implantation blastocyst morule
    4. 4. 4.5 days 6 days
    5. 5. Second week of development: bilaminar germ disc Week of twosWeek of twos • Inner cell mass (embryoblast) – Epiblast – Hypoblast • Trophoblast – Cytotrophoblast – Syncytiotrophoblast • Extraembryonic mesoderm – Somatopleuric mesoderm – Splanchnopleuric mesoderm • Two cavities – Amniotic cavity12 days Amniotic cavity
    6. 6. Day 13
    7. 7. Third week of development: Trilaminar germ disc Gastrulation • Bilamelar germ disc is converted into a trilamelar germ – Ectoderm – Mesoderm – Endoderm • Primitive streak – Thickened linear band of epiblast – 15- to 16-day embryo: clearly visible
    8. 8. Epiblast -> 1.ectoderm 2.mesoderm 3.endoderm 18-day embryo 1.25 mm in length
    9. 9. Derivatives of the ectodermal germ layer 1. Central nervous system 2. Peripheral nervous system 3. Skin, including hair and nails 4. Sensory epithelium of ear, nose, and eye 5. Pituitary, mammary, and sweat glands and enamel of the teeth
    10. 10. Derivatives of the mesodermal germ layer • Connective tissue, cartilage, bone and striated and smooth muscles • heart, blood and lymph vessels and cells • kidney, ovary and testis, genital ducts, serous membranes lining, spleen, and adrenal cortex
    11. 11. Derivatives of the endodermal germ layer 1. Epithelial lining of the gastrointestinal tract, respiratory tract, and urinary bladder 2. Parenchyma of the thyroid, parathyroid, liver and pancreas 3. Epithelial lining of the tympanic cavity and auditory tube
    12. 12. Fate of the primitive streak • intraembryonic mesoderm 을 4 주말까지 만들다가 감소 • insignificant structures in the sacrococcygeal region of the embryo • Sacrococcygeal teratoma
    13. 13. Teratogenesis associated with gastrulation • The beginning of the third week of development, when gastrulation is initiated, is a highly sensitive stage for teratogenic insult. • At this time, fate maps can be made for various organ systems, such as the eyes and brain anlage, and these cell populations may be damaged by teratogens. • For example, high doses of alcohol at this stage kill cells in the anterior midline of the germ disc, producing a deficiency of the midline in craniofacial structures and resulting in holoprosencephaly.
    14. 14. Caudal dysgenesis (sirenomelia) • Insufficient mesoderm in the lumbosacral region of the embryo − Hypoplasia and fusion of lower limb − Vertebral abnormalities − Renal agenesis − Imperforate anus − Anomalies of the genital organs
    15. 15. Formation of the notochord B C
    16. 16. Notochord: 1. Primitive axis of the embryo 2. Induction - neural plate (future nervous system) Fate of the Notochord: – Regress in the vertebral bodies – Intervertebral disc: persist as the nucleus pulposus
    17. 17. 20 days Neurulation includes the formation of the neural plate (day 18-19), neural folds (day 20-21), and the neural tube (day 22-26); the latter will develop into the future brain and spinal cord
    18. 18. Final closure Anterior neuropore: 25th day Posterior neuropore: 27th day
    19. 19. Neural tube defectsNeural tube defects • Most common CNS malformation, 1/1000 births • Primary non-close of the neural tube • Spectrum – Anencephaly – Meningocele – Meningoencephalocele – Meningomyelocele
    20. 20. AnencephalyAnencephaly • Absence of scalp, calvarium, and normal brain -> “frog’s face” • Area cerebrovasculosa • Hypoplastic adrenal glands with absent fetal zone • Recurrence rate: 3-5% • DDx: amniotic disruption sequence Amnion disruption consequence Anencephaly
    21. 21. HoloprosencephalyHoloprosencephaly 4th week, 4mm, 3 vesicle stage 5th week, 8 mm, 5 vesicle stage
    22. 22. LissencephalyLissencephaly • “Smooth brain” • Severity : the absence (agyria) to reduction (pachygyria) of normal gyral pattern. • Classic L./cobblestone L. • Onset : no later than the 12th–16th week of gestation • DDx: immature GA (until 27-28W) •GA 31 wks •46, XX, del(17)(p13) •“Miller-Dieker” syndrome
    23. 23. Formation and migration of neural crest cells in the spinal cord
    24. 24. Neural crest cells • Vulnerable cell population • Easily killed by compounds such as alcohol and retinoic acid. • Deficient in superoxide dismutase and catalase enzymes that are responsible for scavenging free radicals. • Neural crest derivativesNeural crest derivatives  Connective tissue and bones of the face and skull  Dermis in face and neck ☞ Severe craniofacial malformations ☞ Treacher-Collins' Syndrome, DiGeorge anomaly...  Conotruncal septum in the heart ☞ cardiac anomalies including persistent truncus arteriosus, TOF and TGA  Cranial nerve ganglia, spinal ganglia, sympathetic chain and preaortic ganglia, parasympathetic ganglia of the gastrointestinal tract, glial cells, schwann cells, adrenal medulla, C cells of the thyroid gland, arachnoid and pia mater, melanocytes, odontoblasts
    25. 25. Neural crest cells in conotruncal region
    26. 26. MIGRATION PATHWAYS OF NEURAL CREST CELLS from forebrain, midbrain, and hindbrain regions into their final locations (shaded areas) in the pharyngeal arches and face Skeletal structures of the head and face. Mesenchyme for these structures is derived from neural crest (blue), lateral plate mesoderm (yellow), and paraxial mesoderm (red).
    27. 27. Treacher-Collins' Syndrome / mandibulofacial dysostosis • Characterized by malar hypoplasia due to underdevelopment of cheek bones, mandibular hypoplasia, down-slanting eyes and malformed external ears • Normal development and intelligence • AD with variable penetrance • 60% as new mutation www.treachercollins.org/main.ht
    28. 28. Velocardiofacial Syndrome/DiGeorge anomaly • 22q11.2 deletion • “CATCH 22” – Cardiac defects – Abnormal face – Thymic hypoplasia – Cleft palate – Hypocalcemia • Abnormal development of neural crest cells • Specific facial features – low-set ears, wide-set eyes, a small jaw, and a short groove in the upper lip • Etiology – Genetic causes, exposure to retinoic acids, alcohol, and maternal DM
    29. 29. Limb growth and development A. 5-week embryo B. 6-week embryo C. 8-week embryo The hindlimb buds are less well developed than those of the forelimbs. The most sensitive period for teratogen-induced limb malformations is the fourth and fifth weeks of
    30. 30. Nasal pit Lateral nasal prominence Medial nasal prominence 5 주 10 주7 주 6 주
    31. 31. A.B. 6.5-week embryo The palatine shelves are in the vertical position on each side of the tongue. C.D. 7.5-week embryo The tongue has moved downward, and the palatine shelves have reached a horizontal position. E.F. 10-week embryo The two palatine shelves have fused with each other and with the nasal septum. C D FE
    32. 32. A, day 18 B, day 20 C, day 21 D, day 22* Heart tube
    33. 33. Atrial Septation (4-6 weeks) Septum primum ostium primum Interventricular foramen
    34. 34. ostium secundum Septum secundum 35 days
    35. 35. Development of conotruncal ridges and closure of the interventricular foramen 6 weeks Beginning of 7 weeks
    36. 36. End of 7 weeks
    37. 37. Third to eighth week: The embryonic period • Period of organogenesis • Each of three germ layers gives rise to its own tissues and organs. • Major features of the external body form recognizable by the end of the second month

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