Reproductive Medicine Embryology

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jknell
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207837
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Reproductive Medicine Embryology
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2013-03-19 19:26:35
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Reproductive medicine Embriology
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  1. Genes in embryogenesis
    • Sonic hedgehog gene
    • Wnt-7
    • FGF gene
    • Homeobox (Hox) genes
  2. Sonic hedgehog gene
    • Produced at base of limbs in zone of polarizing activity
    • Involved in patterning along anderior-posterior axis
    • Involved in CNS development; mutation can cause holoprosencephaly
  3. Wnt-7 gene
    • Produced at apical ectodermal ridge (thickened ectoderm at distal end of each developing limb)
    • Needed for proper organization along dorsal-ventral axis
  4. FGF gene
    • Produced at apical ectodermal ridge
    • Stimulates mitosis of underlying mesoderm, providing for lengthening of limbs
  5. Homeobox (Hox) genes
    • Involved in segmental organization of embryo in a craniocaudal direction
    • Hox mutations → appendages in wrong locations
  6. Early fetal development
    Day 0, wk1, wk2, wk3, wk3-8, wk 4, wk 8, wk 10
    • Day 0 - fertilization by sperm → zygote, initiating embryogenesis
    • <wk1 - hCG secretion begins after implantation of balstocyst
    • <wk2 - Bilaminar disc (epiblast, hypoblast). 2 weeks = 2 layers
    • <wk3 - trilaminar disk. 3 weeks = 3 layers. Gastrulation. Primitive streak, notochord, mesoderm and its organization, neural plate begin to form
    • Wk3-8 (Embryonic period) - Neural tube formed by neuroectoderm and closed by week 4. Organogenesis. Extremely susceptible to teratogens
    • Wk4 - Heart begins to beat. Upper and lower limb buds begin to form. weeks = 4 limbs
    • Wk8 (Start of fetal period) - fetal movements, fetus looks like a baby
    • Wk10 - Genitalia have male/female characteristics
    • Day 0: fertalization
    • Day 2: Zygote
    • Day 3: Morula
    • Day 5: Blastocyst
    • Day 6: Implantation
  7. Gastrulation
    • Process that forms trilaminar embryonic disc
    • establishes ectoderm, mesoderm, and endoderm germ layers
    • Stars with the epiblast invaginating to form the primitive streak
  8. Ectoderm
    derivatives, function
    • Surface ectoderm:
    • -Adenohypophysis (from Rathke's pouch)
    • -lens of eye
    • -epithelial linings of oral cavity
    • -sensory organs of ear
    • -olfactory epithelium
    • -anal canal below the pectinate line
    • -parotid, sweat, and mammary glands
    • Craniopharyngioma - benign Rathke's pouch tumor with cholesterol crystals, calcifications

    • NeuroectodermThink CNS
    • -Brain (neurohypophysis, CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland)
    • -Retina and optic nerve
    • -Spinal cord

    • Neural crestThink PNS and non-neural structures 
    • -PNS (dorsal root ganglia, cranial nerves, celiac ganglion, Schwann cells, ANS)
    • -Melanocytes
    • -Chromaffin cells of adrenal medulla
    • -Parafollicular (C) cells of thyroid
    • -Schwann cells
    • -pia and arachnoid
    • -bones of the skull
    • -odontoblasts
    • -aorticopulmonary septum
  9. Mesoderm
    derivatives
    • ☒Muscle, bone, connective tissue, serous lining of body cavities (e.g. peritoneum)
    • -Spleen (derived from foregut mesentery)
    • -Cardiovascular structures
    • -Lymphatics
    • -Blood
    • -Wall of gut tube, wall of bladder, urethra
    • -Vagina
    • -Kidneys, adrenal cortex
    • -Dermis
    • -Testes, ovaries

    ☒Notochord induces ectoderm to form neuroectoderm (neural plate)... Its only postatal derivative is the nucleus pulposus of the intervertebral disc

    • **Medosermal defects = VACTERL:
    • -Vertebral defects
    • -Anal atresia
    • -Cardiac defects
    • -Trachio-Esophageal fistula
    • -Renal defects
    • -Limb defects (bone and muscle)
  10. Endoderm
    derivatives
    • Gut tube epithelium (including anal canal above the pectinate line)
    • Luminal epithelial derivatives (lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular cells)
  11. Types of errors in organ morphogenesis
    • Agenesis: Absent organ due to absent premodial tissue
    • Aplasia: Absent organ despite present primordial tissue
    • Deformation: Extrinsic disruption; occurs after the embryonic period
    • Hypoplasia: Incomplete organ development; primordial tissue present
    • Malformation: Intrinsic disruption; occurs during the embryonic period (weeks 3-8)
  12. Teratogens
    Time period
    • Most susceptible in 3rd-8th weeks of pregnancy
    •     (embryonic period → organogenesis)
    • Before week 3: all-or-none effects
    • After week 8: growth and function affected
  13. Teratogens
    medications and substance abuse, effect
    • Alcohol: most common cause of mental retardation; facial abnormalities, microcephaly
    • ACE Inhibitors: renal damage
    • Alkylating agents: Absence of digits, multiple anomalies
    • Aminoglycosides: CNVIII toxicity
    • Cocaine: Intrauterine growth retardation, placental abruption; fetal addiction
    • Diethylstilbestrol (DES): Vaginal clear cell adenocarcinoma, congenital Müllerian anomalies
    • Folate antagonists: Neural tube defects
    • Lithium: Ebstein's anomaly (atrialized right ventricle)
    • Thalidomide: limb defects ("flipper" limbs) Limb defects with "tha-limb-domide"
    • Cigarette smoke: Intrauterine growth retardation/restriction; preterm labor, ADHD
    • Isotretinoin: Spontaneous abortion, hearing and visual impairment
    • Tetracycline: Discolored teeth
    • Warfarin: Fetal bleeding * Don't wage warfare on baby; keep it heppy with heparin (does not cross placenta)
    • Valproate: Inhibition of maternal folate absorption → neural tube defects
    • Phenytoin: Fetal hydantoin syndrome: microcephaly, dysmorphic craniofacial features, hypoplastic nails and distal phalanges, cardiac defects, IUGR, mental retardation
  14. Other teratogens
    • Iodide (lack or excess): Congenital goiter or hypothyroidism (cretinism)
    • Maternal diabetes: Caudal regression syndrome (anal atresia to sirenomelia), congenital heart defects, neural tube defects
    • Vitamin A (Excess): high risk for spontaneous abortion and birth defects (cleft palate, cardiac abnormalities)
    • X-rays: Microcephaly, mental retardation
    • --Infections, antibiotics
  15. Fetal alcohol syndrome
    • Leading cause of congenital malformations in the US
    • Congenital abnormalities: mental retardation, pre- and postnatal development retardation/restriction, microcephaly, holoprosencephaly, facial abnormalities, limb dislocation, heart and lung fistulas
  16. Twinning
    • Dizygotic = 2 eggs, fertilized separately by 2 different sperm
    • -two separate amniotic sacs
    • -two separate placentas (chorions)

    • Monozygotic = 1 fertilized egg that splits into 2 zygotes in early pregnancy
    • -time of split determines number of amniotic sacs and number of placentas
  17. Placenta
    Function, components
    Placenta is the primary site of nutrient and gas exchange between mother and fetus

    • Fetal components:
    • -Cytotrophoblasts
    • -Syncytiotrophoblasts

    • Maternal component
    • -Dicidua basalis
  18. Placenta development
    fetal components
    • Cytotrophoblast: Inner layer of chorionic villi
    • -Cytotrophoblast makes Cells

    • Syncytiotrophoblast: outer layer of chorionic villi
    • -Secretes hCG (structurally similar to LH; stimulates corpus luteum to secrete progesterone during first tirmester)
  19. Placenta
    Maternal components
    • Decidua baasalis: Derived from the endometrium
    • -Maternal blood in lacunae:
  20. Placental testing
    • Amniocentesis: performed at 16 wks for genetic evaluation
    • -evaluate lung maturity
    • -mother >35years
    • -Abnormal maternal serum QUAD screening
    • -Rh-sensitized pregnancy to detect fetal blood type or fetal hemolysis
    • Risk: 1% maternal/fetal hemorrhage

    • Chorionic villous sampling:
    • -12 weeks
    • Risks: 1% fetal loss
  21. Umbilical cord
    structure
    • Umbilical arteries (2) - return deoxygenated blood from fetal internal iliac arteries to placenta
    • Umbilical vein (1) - supplies oxygenated blood from placenta to fetus; drains via ductus venosus into IVC
    • Single umbilical artery is associated with congenital and chromosomal anomalies
    • Umbilical arteries and veins are derived from allantois
  22. Urachal duct
    • -3rd week: yolk sac forms allantois, extends into urogenital sinus
    • -Allantois becomes urachus (duct between bladder and yolk sac)

    • Failure of urachus to obliterate:
    • -Patent urachus: urine discharge from umbilicus
    • -Vesicourachal diverticulum: outpouching of bladder
  23. Vitelline duct
    7th week: obliteration of vitelline duct (omphalo-mesenteric duct), which connects yolk sac to midgut lumen

    • Failure of vitelline duct to close:
    • -Vitelline fistula: Meconium discharge from umbilicus
    • -Meckel's diverticulum: partial closure, with patent portion attached to ileum. May have ectopic gastric mucosa → melena, periumbilical pain, and ulcer
  24. Aortic arch derivatives
    arterial system
    • 1st: part of maxillary artery (branch of external carotid) **1st arch is maximal
    • 2nd: Stapedial artery and hyoid artery **Second = Stapedial
    • 3rd: Common Carotid artery and proximal part of internal Carotid artery **C is 3rd leter of alphabet
    • 4th: On left, aortic arch; on right, proximal part of right subclavian artery **4th arch (4 limbs) = systemic
    • 6th: proximal part of pulmonary arteries and (on left only) ductus arteriosus ** 6th arch = pulmonary artery and pulmonary-to-systemic shunt (ductus arteriosus)
  25. Branchial apparatus
    aka pharyngeal apparatus
    Branchial clefts, arches, and pouches

    • Branchial clefts: derived from ectoderm
    • -aka Branchial grooves

    Branchial arches: derived from mesoderm (muscles, arteries) and neural crest (bones, cartilage)

    Branchial pouches: derived from endoderm

    • CAP covers outside from inside:
    • Clefts = ectoderm
    • Arches = mesoderm
    • Pouches = endoderm

  26. Branchial cleft derivatives
    • -1st cleft develops into external auditory meatus
    • -2nd - 4th clefts form temporary cervical sinus, whcih are obliterated by proliferation of 2nd arch mesenchyme

    Persistent cervical sinus → branchial cleft cysts within lateral neck
  27. Branchial arch derivatives
    1st arch
    • Cartilage:
    • -Mechel's cartilage: Mandible, Malleus, incus, spheno-Mandibular ligament

    • Muscles:
    • -Muscles of Mastication (temporalis, Masseter, lateral and Medial pterygoids)
    • -Mylohyoid
    • -Anterior belly of digastric
    • -Tensor tympani
    • -Tensor veli palatini

    • Nerves:
    • -CN V2 and V3 (chew)

    • Abnormalities/Comments:
    • Treacher Collins syndrome: 1st-arch neural crest fails to migrate → mandibular hypoplasia, facial abnormalities
  28. Branchial arch derivatives
    2nd arch
    • Cartilage:
    • -Reiechert's cartillage: Stapes, Styloid process, lesser horn of hyoid, Stylohyoid ligament

    • Muscles:
    • -Muscles of facial expression
    • -Stapedius
    • -Stylohoid
    • -Posterior belly of digastric

    • Nerves:
    • -CN VII (facial expression)
    • smile
  29. Branchial arches derivatives
    3rd arch
    • Cartilage:
    • -Greater horn of hyoid

    • Muscles:
    • -Stylopharyngeus (think of styopharyngeus innervated by glossopharyngeal nerve)

    • Nerves:
    • -CN IX (Stylopharyngeus)
    • Swallow stylishly

    • Abnormalities/comments:
    • Congenital pharyngocutaneous fistula:
    • -Persistence of cleft and pouch → fistula between tonsillar area, cleft in lateral neck
  30. Branchial arch derivatives
    4th-6th arches
    • Cartilage:
    • -Thyroid
    • -Cricoid
    • -arytenoids
    • -corniculate
    • -cuneiform

    • Muscles:
    • -4th: most pharyngeal constrictors; cricothyroid, levator veli palatini
    • -6th: all intrinsic muscles of larynx except cricothyroid

    • Nerves:
    • -4th: CN X (superior laryngeal branch) Simply swallow
    • -6th: CN X (recurrent laryngeal branch) speak

    • Abnormalities/comments:
    • -Arches 3 and 4 form posterior 1/3 of tongue
    • -Arch 5 makes no major developmental contributions
  31. Branchial arch
    pneumonic
    When at the restaurant of the golden arches, children tend to first chew (1), then smile (2), then swallow stylishly (3) or simply swallow (4), and then speak (6)
  32. Branchial pouch derivatives
    • 1st pouch: middle ear cavity, eustachian tube, mastoid air cells (endoderm-lined structures of ear)
    • 2nd pouch: epithelial lining of palantine tonsile
    • 3rd pouch:-Dorsal wings: develop into inferior parathyroids;-Ventral wings: develops into thymus
    • 4th pouch: Dorsal wings develop into superior parathyroids
  33. Branchial pouch derivatives
    pneumonic
    • -3rd pouch contributes to 3 structures (thymus, left and right inferior parathyroids)
    • -3rd pouch structures end up below 4th pouch structures

    • Ear, tonsils, bottom-to top:
    • 1. (ear)
    • 2. (tonsils)
    • 3. dorsal (bottom = inferior parathyroid)
    • 3. ventral (to = thymus)
    • 4. (top = superior parathyroids)
  34. DiGeorge syndrome
    • Aberrant development of 3rd and 4th pouches:
    • -T cell deficiency (thymic aplasia)
    • -hypocalcemia (failure of parathyroid development)
  35. MEN 2A
    • Mutation of germline RET (neural crest cells):
    • -Adrenal medulla (pheochromocytoma)
    • -Parathyroid tumor: 3rd/4th pharyngeal pouch
    • -Parafollicular cells (medullary thyroid cancer): derived from neural crest cells; associated with 4th/5th pharyngeal pouches
  36. Cleft lip
    • Failure of fusion of maxillary and medial nasal processes (formation of 1° palate)
    • Often occurs together with cleft palate
  37. Cleft palate
    • Failure of fusion of the lateral palatine processes, nasal septum, and/or median palatine process (formation of 2° palate)
  38. Female genital embryology
    • Default development
    • Mesonephric duct generates
    • Paramesonephric duct develops
  39. Male genital embryology
    • SRY on Y chromosome:
    • -Produces testis (determining factor for testes development)

    Sertoli cells: secrete Müllerian inhibitory factor (MIF) that suppresses development of paramesonephric ducts

    Leydig cells secrete androgens that stimulate the development of mesonephritc ducts

  40. Paramesonephric duct
    Müllerian duct
    • Develops into female internal structures:
    • -fallopian tubes
    • -uterus
    • -upper portion of vagina (lower from the urogenital sinus)

    Anomalies result in anatomical defects hat may present as primary amenorrhea in females with fully developed secondary sexual characteristics
  41. Mesonephric duct
    Wolffian
    • Develops into male internal structures:
    • -Seminal vesicles
    • -Epididymis
    • -Ejaculatory duct
    • -Ductus deferens

    (SEED)

    *not prostate
  42. Bicornuate uterus
    • Results from incomplete fusion of the paramesonephric ducts
    • Can lead to urinary tract anomalities and miscarriage
  43. SRY gene
    • 1. No Sertoli cells or lack of MIF: Develop both male and femal internal genitalia and male external genetalia
    • 2. 5α-reductase deficiency: male internal genitalia, ambiguous external genitalia until puberty
  44. Ambiguous genitalia
    DHT vs estrogen
  45. Ambiguous genitalia
    DHT vs estrogen
  46. Hypospadias
    • Abnormal opening of the penile urethra on the inferior (ventral) side of penis
    • Due to failure of urethral folds to close
    • More common than epispadius
    • Fix to prevent UTI
  47. Epispadias
    • Abnormal opening of penile urethral on superior (dorsal) side of penis
    • Due to faulty positioning of genital tubercle
    • Exstrophy of the bladder is associated with Epispadias
    • When you have Epispadias, you hit your Eye when you pEE.
  48. Descent of testes and ovaries
    Gubernaculum, processus vaginalis
    • Gubernaculum (band of fibrous tissue)
    • Male remnant: Anchors testes within scrotum
    • Female remnant: Ovarian ligament + round ligament of uterus

    • Processus vaginalis (evagination of peritoneum)
    • Male remnant: Forms tunica vaginalis
    • Femal remnant: obliterated
  49. Name the developmental structure:
    • Supplies oxygenated blood to the fetus: umbilical vein
    • Removes nitrogenous waste from the fetal bladder: urachus
    • Fetal placental structure that secretes hCG: syncytiotrophoblast
    • Maternal component of the placenta: Decidua
    • Returns deoxygenated blood from the fetal internal iliac artery: umbilical arteries

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