Reproductive - Embryology

Question 1

Important genes of embryogenesis

• Sonic hedgehog gene
  
  • Produced…
  • Function(s)
• Wnt-7 gene
  
  • Produced…
  • Function(s)
  • Mutation(s) –>
• FGF gene
  
  • Produced…
  • Function(s)
• Homeobox (Hox) genes
  
  • Function(s)
  • Mutation(s) –>

Answer 1

• Sonic hedgehog gene
  
  • Produced at base of limbs in zone of polarizing activity.
  • Function(s)
    
    • Involved in patterning along anterior-posterior axis.
    • Involved in CNS development
  • Mutation can cause holoprosencephaly.
• Wnt-7 gene
  
  • Produced at apical ectodermal ridge (thickened ectoderm at distal end of each developing limb).
  • Necessary for proper organization along dorsal-ventral axis.
• FGF gene
  
  • Produced at apical ectodermal ridge.
  • Stimulates mitosis of underlying mesoderm, providing for lengthening of limbs.
• Homeobox (Hox) genes
  
  • Involved in segmental organization of embryo in a craniocaudal direction.
  • Hox mutations –>Ž appendages in wrong locations.

Question 2

Early fetal development (552)

• Day 0
• Within week 1
• Within week 2
• Within week 3
• Weeks 3–8 (embryonic period)
• Week 4
• Week 6
• Week 10

Answer 2

• Day 0
  
  • Fertilization by sperm, forming zygote, initiating embryogenesis.
• Within week 1
  
  • hCG secretion begins around the time of implantation of blastocyst.
• Within week 2
  
  • Bilaminar disc (epiblast, hypoblast).
    
    • 2 weeks = 2 layers.
• Within week 3
  
  • Trilaminar disc.
    
    • 3 weeks = 3 layers.
  • Gastrulation.
  • Primitive streak, notochord, mesoderm and its organization, and neural plate begin to form.
• Weeks 3–8 (embryonic period)
  
  • Neural tube formed by neuroectoderm and closes by week 4.
  • Organogenesis.
  • Extremely susceptible to teratogens.
• Week 4
  
  • Heart begins to beat.
  • Upper and lower limb buds begin to form.
    
    • 4 weeks = 4 limbs.
• Week 6
  
  • Fetal cardiac activity visible by transvaginal ultrasound.
• Week 10
  
  • Genitalia have male/female characteristics.

Question 3

Gastrulation

Answer 3

• Process that forms the trilaminar embryonic disc.
• Establishes the ectoderm, mesoderm, and endoderm germ layers.
• Starts with the epiblast invaginating to form the primitive streak.

Question 4

Embryologic derivatives:
Surface ectoderm

• Derivatives
• Craniopharyngioma

Answer 4

• Derivatives
  
  • All Epidermis PALE
  • Adenohypophysis (from Rathke pouch)
  • Epidermis
  • Parotid, sweat, and mammary glands
  • Anal canal below the pectinate line
  • Lens of eye
  • Epithelial linings of oral cavity, sensory organs of ear, and olfactory epithelium
• Craniopharyngioma
  
  • Benign Rathke pouch tumor with cholesterol crystals, calcifications.

Question 5

Embryologic derivatives:
Neuroectoderm

Answer 5

• Brain (neurohypophysis, CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland)
• Retina and optic nerve
• Spinal cord
• Neuroectoderm—think CNS.

Question 6

Embryologic derivatives:
Neural crest ectoderm

Answer 6

• BAM, COPPP
• Bones of the skull
• Aorticopulmonary septum
• Melanocytes
• Chromaffin cells of adrenal medulla
• Odontoblasts
• PNS (dorsal root ganglia, cranial nerves, celiac ganglion, Schwann cells, ANS)
• Parafollicular (C) cells of thyroid
• Pia and arachnoid
• Neural crest—think PNS and non-neural structures nearby.

Question 7

Embryologic derivatives:
Mesoderm

• Derivatives
• Notochord
• Mesodermal defects

Answer 7

• Derivatives
  
  • Muscle
  • Bone
  • Connective tissue
  • Serous linings of body cavities (e.g., peritoneum)
  • Spleen (derived from foregut mesentery)
  • Cardiovascular structures
  • Lymphatics
  • Blood
  • Wall of gut tube
  • Vagina
  • Kidneys
  • Adrenal cortex
  • Dermis
  • Testes
  • Ovaries
• Notochord
  
  • Induces ectoderm to form neuroectoderm (neural plate).
  • Its only postnatal derivative is the nucleus pulposus of the intervertebral disc.
• Mesodermal defects (VACTERL)
  
  • Vertebral defects
  • Anal atresia
  • Cardiac defects
  • Tracheo-Esophageal fistula
  • Renal defects
  • Limb defects (bone and muscle)

Question 8

Embryologic derivatives:
Endoderm

Answer 8

• Gut tube epithelium (including anal canal above the pectinate line)
• Most of urethra (derived from urogenital sinus)
• Luminal epithelial derivatives (e.g., lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular cells)

Question 9

Types of errors in organ morphogenesis

• Agenesis
• Aplasia
• Hypoplasia
• Deformation
• Disruption
• Malformation
• Sequence

Answer 9

• Agenesis
  
  • Absent organ due to absent primordial tissue.
• Aplasia
  
  • Absent organ despite presence of primordial tissue.
• Hypoplasia
  
  • Incomplete organ development
  • Primordial tissue present.
• Deformation
  
  • Extrinsic disruption
  • Occurs after the embryonic period.
• Disruption
  
  • 2° breakdown of a previously normal tissue or structure
  • e.g., amniotic band syndrome
• Malformation
  
  • Intrinsic disruption
  • Occurs during the embryonic period (weeks 3–8).
• Sequence
  
  • Abnormalities result from a single 1° embryological event
  • e.g., oligohydramnios –>Ž Potter sequence

Question 10

Teratogens

• When most susceptible
• Before
• After

Answer 10

• Most susceptible in 3rd–8th weeks (embryonic period—organogenesis) of pregnancy.
• Before week 3: all-or-none effects.
• After week 8: growth and function affected.

Question 11

Effects of these teratogens (medications) on fetus

• ACE inhibitors
• Alkylating agents
• Aminoglycosides
• Carbamazepine
• Diethylstilbestrol (DES)
• Folate antagonists
• Lithium

Answer 11

• ACE inhibitors
  
  • Renal damage
• Alkylating agents
  
  • Absence of digits, multiple anomalies
• Aminoglycosides
  
  • CN VIII toxicity
  • A mean guy hit the baby in the ear.
• Carbamazepine
  
  • Neural tube defects, craniofacial defects, fingernail hypoplasia, developmental delay, IUGR
• Diethylstilbestrol (DES)
  
  • Vaginal clear cell adenocarcinoma, congenital Müllerian anomalies
• Folate antagonists
  
  • Neural tube defects
• Lithium
  
  • Ebstein anomaly (atrialized right ventricle)

Question 12

Effects of these teratogens (medications) on fetus

• Methimazole
• Phenytoin
• Tetracyclines
• Thalidomide
• Valproate
• Warfarin

Answer 12

• Methimazole
  
  • Aplasia cutis congenita
• Phenytoin
  
  • Fetal hydantoin syndrome: microcephaly, dysmorphic craniofacial features, hypoplastic nails and distal phalanges, cardiac defects, IUGR, intellectual disability
• Tetracyclines
  
  • Discolored teeth
  • “Teethracyclines”
• Thalidomide
  
  • Limb defects (phocomelia, micromelia—“flipper” limbs)
  • Limb defects with “tha-_limb_-domide.”
• Valproate
  
  • Inhibition of maternal folate absorption –>Ž neural tube defects
  • Valproate** inhibits folate absorption**
• Warfarin
  
  • Bone deformities, fetal hemorrhage, abortion, ophthalmologic abnormalities
  • Do not wage warfare on the baby; keep it heppy with heparin (does not cross placenta).

Question 13

Effects of these teratogens (substance abuse) on fetus

• Alcohol
• Cocaine
• Smoking (nicotine, CO)

Answer 13

• Alcohol
  
  • Common cause of birth defects and intellectual disability
  • Fetal alcohol syndrome
• Cocaine
  
  • Abnormal fetal growth and fetal addiction
  • Placental abruption
• Smoking (nicotine, CO)
  
  • A leading cause of low birth weight in developed countries
  • Associated with preterm labor, placental problems, IUGR, ADHD

Question 14

Effects of these teratogens on fetus

• Iodine (lack or excess)
• Maternal diabetes
• Vitamin A (excess)
• X-rays
• Other

Answer 14

• Iodine (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)
  
  • Extremely high risk for spontaneous abortions and birth defects (cleft palate, cardiac abnormalities)
• X-rays
  
  • Microcephaly, intellectual disability
• Other
  
  • Fetal infections and certain antibiotics can also cause congenital malformations

Question 15

Fetal alcohol syndrome

• One of the leading causes of…
• Newborns of mothers who consumed significant amounts of alcohol during pregnancy have an increased incidence of…

Answer 15

• One of the leading causes of congenital malformations in the United States.
• Newborns of mothers who consumed significant amounts of alcohol during pregnancy have an increased incidence of congenital abnormalities, including…
  
  • Intellectual disability
  • Pre- and postnatal developmental retardation
  • Microcephaly
  • Holoprosencephaly
  • Facial abnormalities (smooth philtrum, thin upper lip, small palpebral fissures, hypertelorism)
  • Limb dislocation
  • Heart defects

Question 16

Twinning (555)

• Dizygotic twins
  
  • Arise from…
  • Will have…
• Monozygotic twins
  
  • Arise from…
• The degree of separation between monozygotic twins depends on…
• The timing of this separation determines…

Answer 16

• Dizygotic twins
  
  • Arise from 2 eggs that are separately fertilized by 2 different sperm (always 2 zygotes)
  • Will have 2 separate amniotic sacs and 2 separate placentas (chorions)
• Monozygotic twins
  
  • Arise from 1 fertilized egg (1 egg + 1 sperm) that splits into 2 zygotes in early pregnancy.
• The degree of separation between monozygotic twins depends on when the fertilized egg splits into 2 zygotes.
• The timing of this separation determines the number of chorions and the number of amnions.

Question 17

Twinning (555)

• 0-4 days
• 4-8 days
• 8-12 days
• > 13 days

Answer 17

• 0-4 days (2 cell stage –> morula)
  
  • Diamniotic
  • Dichorionic
• 4-8 days (morula –> blastocyst)
  
  • Diamniotic
  • Monochorionic
• 8-12 days (blastocyst –> formed embryonic disc)
  
  • Monoamniotic
  • Monochorionic
• > 13 days (formed embryonic disc –> dichorionic / diamniotic)
  
  • Monoamnioitc
  • Monochorionic
  • Conjoined twins

Question 18

Placental development

• 1º site of…
• For each
  
  • Fetal or maternal component
  • Definition
• Cytotrophoblast
• Syncytiotrophoblast
• Decidua basalis

Answer 18

• 1º site of nutrient and gas exchange between mother and fetus.
• Cytotrophoblast
  
  • Fetal component
  • Definition
    
    • Inner layer of chorionic villi.
    • Cytotrophoblast makes Cells.
• Syncytiotrophoblast
  
  • Fetal component
  • Definition
    
    • Outer layer of chorionic villi
    • Secretes hCG (structurally similar to LH; stimulates corpus luteum to secrete progesterone during first trimester).
• Decidua basalis
  
  • Maternal component
  • Definition
    
    • Derived from the endometrium.
    • Maternal blood in lacunae.

Question 19

Umbilical cord

• Umbilical arteries
• Umbilical veins
• Umbilical artery and vein derivation

Answer 19

• Umbilical arteries (2)
  
  • Return deoxygenated blood from fetal internal iliac arteries to placenta [A].
  • Single umbilical artery is associated with congenital and chromosomal anomalies.
• Umbilical vein (1)
  
  • Supplies oxygenated blood from placenta to fetus
  • Drains into IVC via liver or via ductus venosus.
• Umbilical arteries and veins are derived from allantois.

Question 20

Urachus

• Derivation
• Failure of urachus to obliterate results in:

Answer 20

• Derivation
  
  • In the 3rd week the yolk sac forms the allantois, which extends into the urogenital sinus.
  • Allantois becomes the urachus, a duct between fetal bladder and yolk sac.
• Failure of urachus to obliterate results in:
  
  • Patent urachus
    
    • Urine discharge from umbilicus.
  • Urachal cyst
    
    • Partial failure of urachus to obliterate
    • Fluid-filled cavity lined with uroepithelium, between umbilicus and bladder.
    • Can lead to infection, adenocarcinoma.
  • Vesicourachal diverticulum
    
    • Outpouching of bladder.

Question 21

Vitelline duct

• Derivation
• Failure of vitelline duct to close results in:

Answer 21

• Derivation
  
  • 7th week—obliteration of vitelline duct (omphalo-mesenteric duct), which connects yolk sac to midgut lumen.
• Failure of vitelline duct to close results in:
  
  • Vitelline fistula
    
    • –>Ž meconium discharge from umbilicus.
  • Meckel diverticulum
    
    • Partial closure, with patent portion attached to ileum (true diverticulum).
    • May have ectopic gastric mucosa and/or pancreatic tissue –>ŽŽ melena, periumbilical pain, and ulcers.

Question 22

Aortic arch derivatives

• Develop into…
• 1st
• 2nd
• 3rd
• 4th
• 6th

Answer 22

• Develop into the 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 letter 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 and the pulmonary-to-systemic shunt (ductus arteriosus).

Question 23

Branchial apparatus

• Also called…
• Composed of…

Answer 23

• Also called pharyngeal apparatus.
• Composed of…
  
  • Branchial clefts
    
    • Derived from ectoderm.
    • Also called branchial grooves.
  • Branchial arches
    
    • Derived from mesoderm (muscles, arteries) and neural crest (bones, cartilage).
  • Branchial pouches
    
    • Derived from endoderm.
• CAP covers outside to inside:
  
  • Clefts = ectoderm
  • Arches = mesoderm
  • Pouches = endoderm

Question 24

Branchial cleft derivatives

• 1st cleft develops into…
• 2nd through 4th clefts form…
• Persistent cervical sinus –>

Answer 24

• 1st cleft develops into external auditory meatus.
• 2nd through 4th clefts form temporary cervical sinuses, which are obliterated by proliferation of 2nd arch mesenchyme.
• Persistent cervical sinus –>Ž branchial cleft cyst within lateral neck.

Question 25

Branchial arch derivatives: 1st arch * Cartilage * Muscles * Nerves * Abnormalities / comments

Answer 25

* Cartilage * **_M_**eckel cartilage: **_M_**andible, **_M_**alleus, incus, spheno-**_M_**andibular ligament * Muscles * **_M_**uscles of **_M_**astication (temporalis, Masseter, lateral and **_M_**edial pterygoids), **_M_**ylohyoid, 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 --\>Ž mandibular hypoplasia, facial abnormalities

Question 26

Branchial arch derivatives: 2nd arch * Cartilage * Muscles * Nerves * Abnormalities / comments

Answer 26

* Cartilage * Reichert cartilage: **_S_**tapes, **_S_**tyloid process, lesser horn of hyoid, **_S_**tylohyoid ligament * Muscles * Muscles of facial expression, **_S_**tapedius, **_S_**tylohyoid, platy**_S_**ma, belly of digastric * Nerves * CN VII (facial expression) **_smile_** * Abnormalities / comments * **Congenital pharyngocutaneous fistula**: persistence of cleft and pouch Ž--\> fistula between tonsillar area and lateral neck

Question 27

Branchial arch derivatives: 3rd arch * Cartilage * Muscles * Nerves

Answer 27

* Cartilage * Cartilage: greater horn of hyoid * Muscles * Stylopharyngeus (think of stylo**pharyngeus** innervated by glosso**pharyngeal** nerve) * Nerves * CN IX (**stylo**pharyngeus) **swallow styl**ishly

Question 28

Branchial arch derivatives: 4th–6th arches * Cartilage * Muscles * 4th arch * 6th arch * Nerves * 4th arch * 6th arch * Abnormalities / comments * Arches 3 and 4 * Arch 5

Answer 28

* Cartilage * Cartilages: thyroid, cricoid, arytenoids, corniculate, cuneiform * Muscles * 4th arch: most pharyngeal constrictors; cricothyroid, levator veli palatini * 6th arch: all intrinsic muscles of larynx except cricothyroid * Nerves * 4th arch: CN X (superior laryngeal branch) **simply swallow** * 6th arch: 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

Question 29

Branchial arch derivatives * Nerves * Mnemonic

Answer 29

* Nerves * These are the only CNs with both motor and sensory components (except V2, which is sensory only). * Mnemonic * **When at the restaurant of the golden _arches_, children tend to first _chew_ (1), then _smile_ (2), then _swallow styl_ishly (3) or _simply swallow_ (4), and then _speak_ (6).**

Question 30

Branchial pouch derivatives * 1st pouch * 2nd pouch * 3rd pouch * 4th pouch

Answer 30

* 1st pouch * Develops into middle ear cavity, eustachian tube, mastoid air cells. * 1st pouch contributes to endoderm-lined structures of ear. * 2nd pouch * Develops into epithelial lining of palatine tonsil. * 3rd pouch * Dorsal wings—develops into **inferior** parathyroids. * Ventral wings—develops into thymus. * **_3_**rd pouch contributes to **_3_** structures (thymus, left and right inferior parathyroids). * 3rd-pouch structures end up **below** 4th-pouch structures. * 4th pouch * Dorsal wings—develops into **superior** parathyroids. * **Ear, tonsils, bottom-to-top:** * 1 (**_ear_**), * 2 (**_tonsils_**), * 3 dorsal (**_bottom_** for inferior parathyroids), * 3 ventral (**_to_** = **_t_**hymus), * 4 (**_top_** = superior parathyroids).

Question 31

DiGeorge syndrome

Answer 31

* Aberrant development of 3rd and 4th pouches Ž--\> T-cell deficiency (thymic aplasia) and hypocalcemia (failure of parathyroid development). * Associated with cardiac defects (conotruncal anomalies).

Question 32

MEN 2A

Answer 32

* 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 the 4th/5th pharyngeal pouches.

Question 33

Cleft lip and cleft palate * Cleft lip * Cleft palate * Comparison

Answer 33

* **Cleft lip** * Failure of fusion of the maxillary and medial nasal processes (formation of 1° palate). * **Cleft palate** * Failure of fusion of the two lateral palatine processes or failure of fusion of lateral palatine processes with the nasal septum and/or median palatine process (formation of 2° palate). * Comparison * Cleft lip and cleft palate have two distinct etiologies, but often occur together.

Question 34

Genital embryology * Female * Development * Mesonephric duct * Paramesonephric duct * Male * SRY gene * Sertoli cells * Leydig cells

Answer 34

* Female * Default development. * Mesonephric duct degenerates * Paramesonephric duct develops. * Male * SRY gene on Y chromosome—produces testisdetermining factor (testes development). * Sertoli cells secrete Müllerian inhibitory factor (MIF) that suppresses development of paramesonephric ducts. * Leydig cells secrete androgens that stimulate the development of mesonephric ducts.

Question 35

Genital embryology * Paramesonephric (Müllerian) duct * Mesonephric (Wolffian) duct * Bicornuate uterus

Answer 35

* Paramesonephric (Müllerian) duct * Develops into female internal structures * Fallopian tubes, uterus, and upper portion of vagina (lower portion from urogenital sinus). * Müllerian duct abnormalities result in anatomical defects that may present as 1° amenorrhea in females with fully developed 2° sexual characteristics (indicator of functional ovaries). * Mesonephric (Wolffian) duct * Develops into male internal structures (except prostate) * **_S_**eminal vesicles, **_E_**pididymis, **_E_**jaculatory duct, and **_D_**uctus deferens (**_SEED_**). * Bicornuate uterus * Results from incomplete fusion of the paramesonephric ducts (vs. complete failure of fusion, resulting in double uterus and vagina). * Can lead to anatomic defects --\>Ž recurrent miscarriages.

Question 36

SRY gene * No Sertoli cells or lack of Müllerian inhibitory factor * 5α-reductase deficiency

Answer 36

1. No Sertoli cells or lack of Müllerian inhibitory factor * Develop both male and female internal genitalia and male external genitalia 2. 5α-reductase deficiency * Inability to convert testosterone into DHT * Male internal genitalia, ambiguous external genitalia until puberty (when increase testosterone levels cause masculinization)

Question 37

Male/female genital homologs (562) * For each * Dihydrotestosterone (male) --\> * Estrogen (female) --\> * Genital tubercle * Urogenital sinus * Urogenital folds * Labioscrotal swelling

Answer 37

* Genital tubercle * _Dihydrotestosterone_ --\> glans penis, corpus cavernosum, spongiosum * _Estrogen_ --\> glans clitoris, vestibular bulbs * Urogenital sinus * _Dihydrotestosterone_ --\> bulbourethral glands (of Cowper), prostate gland * _Estrogen_ --\> greater vestibular glands (of Bartholin), urethral and paraurethral glands (of Skene) * Urogenital folds * _Dihydrotestosterone_ --\> ventral shaft of penis (penile urethra) * _Estrogen_ --\> labia minora * Labioscrotal swelling * _Dihydrotestosterone_ --\> scrotum * _Estrogen_ --\> labia majora

Question 38

Hypospadias

Answer 38

* Congenital penile abnormality * Abnormal opening of penile urethra on **inferior** (ventral) side of penis due to failure of urethral folds to close. * Hypospadias is more common than epispadias. * Fix hypospadias to prevent UTIs. * **_Hypo_ is _below_.**

Question 39

Epispadias

Answer 39

* Congenital penile abnormality * Abnormal opening of penile urethra on superior (dorsal) side of penis due to faulty positioning of genital tubercle. * **_E_**xstrophy of the bladder is associated with **_E_**pispadias. * **When you have **_E_**pispadias, you hit your **_E_**ye when you p**_EE_**.**

Question 40

Descent of testes and ovaries * For each * Male remnant * Female remnant * Gubernaculum (band of fibrous tissue) * Processus vaginalis (evagination of peritoneum)

Answer 40

* 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. * _Female remnant_: Obliterated.