First Aid: Reproductive Embryology Flashcards
List of important genes of embryogenesis
- Sonic Hedgehog gene
- WNT-7 gene
- Fibroblast growth factor (FGF) gene
- Homeobox (Hox) genes
Description of the Sonic Hedgehog gene
- Produced at the base of limbs in zone of polarizing activity
- Involved in patterning along anteroposterior axis and CNS development
Where is Sonic Hedgehog produced?
Produced at the base of limbs in the Zone of Polarizing Actibity (ZPA)
What is the function of Sonic Hedgehog gene
Involved in patterning along the anteroposterior axis and CNS development
What happens with a mutation in Sonic Hedgehog
Mutation can cause holoprosencephaly
What is WNT-7 gene
- Produced at the apical ectodermal ridge (thickened ectoderm at distal end of each developing limb).
- Necessary for proper organization along the dorsal-ventral axis
Where is Wnt-7 produced?
Produced at apical ectodermal ridge (thickened ectoderm at distal end of each developing limb)
What is the function of Wnt-7?
Necessary for proper organization along the dorsal-ventral axis
FGF AKA
Fibroblast Growth Factor
Description of FGF
- Produced at apical ectodermal ridge
- Stimulates mitosis of underlying mesoderm, providing for the legnthening of limbs
- “Look at that Fetus, Growing Fingers”
FGF is produced where?
Produced at the apical ectodermal ridge
FGF function
Stimulates mitosis of underlying mesoderm, providing for the lengthening of limbs
FGF Nmemonic
“Look at that Fetus, Growing Fingers”
Description of Homeobox (Hox) genes
- Involved in segmental organization of embryo in a craniocaudal direction
- Code for transcription factors
- Hox mutations result in -> appendages in the wrong locations
Hox genes AKA
Homeobox genes
Hox genes gunction
- Involved in segmental organization of embryo in craniocaudal direction
- Code for transcription factors
Hox gene mutations result in
Appendages in wrong locations
Describe early embryonic development
Describe Early fetal development within the first week
- hCG secretion begins around the time of implantation of blastocyst
- Blastocyst“sticks” at day 6
Describe Early fetal development within week 2
- Bilaminar disc (epiblast, hypoblast)
- 2 weeks = 2 layers
Describe Early fetal development within week 3
- Gastrulation forms trilaminar embryonic disc
- Cells from epiblast invaginate -> primitive streak -> endoderm, mesoderm, ectoderm
- Notochord arises from midline mesoderm; overlying ectoderm becomes neural plate
Describe Early fetal development weeks 3-8 (embryonic period)
- Neural tube formed by neuroectoderm and closes by week 4
- Organogenesis
- During this time embryo is extremely susceptible to teratogens
Describe Early fetal development week 4
- Heart begins to beat
- Upper and lower limb buds begin to form
- 4 weeks = 4 limbs and 4 heart chambers
When does the heart begin to beat?
4 weeks
When do the upper and lower limb buds begin to form?
4 weeks
Describe Early fetal development week 6
Fetal cardiac activity visible by transvaginal ultrasound
Describe Early fetal development week 8
- Fetal movements start
- Gait at week 8
Describe Early fetal development week 10
- Genitalia have male/female characteristics
- week 10 = Tenitalia (genitalia)
When do genitalia have male/female characteristics?
Week 10
What are the main embryonic derivatives?
- Ectoderm
- Mesoderm
- Endoderm
Components of ectoderm
- Surface ectoderm
- Neural tube
- Neural crest
Surface ectoderm derivatives
10 listed
- Epidermis
- Adenohypophysis AKA anterior pituitary (from Rathke pouch)
- Lens of eye
- Epithelial linings of oral cavity
- Sensory organs of the ear
- Olfactory epithelium
- Anal canal below below the pectinate line
- Parotid glands
- Sweat glands
- Mammary glands
Issues with surface ectoderm
Craniopharyngioma - benign Rathke pouch tumor with cholesterol crystals, calcifications
Neural tube derivatives
Neuroectoderm (think CNS)
- Brain
- Neurohypophysis
- CNS neurons
- Oligodendrocytes
- Astrocytes
- Ependymal cells
- pineal glands
- retina
- Spinal cord
Craniopharyngioma embronic origin
Surface ectoderm
What is Craniopharyngioma?
Benign Rathke pouch tumor with cholesterol crystals and calcifications
Neural crest derivatives
- Melanocytes
- Myenteric (Auerbach) plexus
- Odontoblasts
- Endocardial cushions
- Laryngeal cartilage
- Parafollicular (C) cells of the thyroid
- PNS (dorsal root ganglia, cranial nerves, autonomic ganglia)
- Adrenal medulla and all ganglia
- Spiral membrane (aorticopulmonary septum)
- Schwann cells
- Pia and arachnoid
- bones of skull
MMOtEL PPASS
Neural crest - think PNS and Non-neural structures nearby
Mesoderm derivatives
- Muscle
- Bone
- Connective tissue
- serous linings of body cavities (eg peritoneum, pericardium, pleura)
- Spleen (derived from foregut mesentary)
- cardiovascular structures
- lymphatics
- blood
- wall of gut tube
- upper vagina
- kidneys
- adrenal cortex
- dermis
- testis
- ovaries
- Notochord induces ectoderm to form neuroectoderm (neural plate); its only postnatal derivative is the nuclues pulposus of the intervertebral disc
Mesoderm derivatives Nmemonic
Middle/”meat” layer
Mesodermal defects = VACTERL
- Vertebral defects
- Anal atresia
- Cardiac defects
- Tracheo-Esophageal fistula
- Renal defects
- Limb defects (bone and muscle)
Endoderm derivatives
- Gut tube epithelium (including anal canal above the pectinate line)
- Most of the urethra and lower vagina (Derived from urogenital sinus)
- Luminal epithelial derivatives (eg lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular cells)
Endoderm = “Enternal” layer
What are the types of errors in morphogenesis?
7 listed
- Agenesis
- Aplasia
- Hypoplasia
- Disruption
- Deformation
- Malformation
- Sequence
What is agenesis
Type of error in morphogenesis where:
Absent organ due to absent primordial tissue
What is aplasia?
Type of error in morphogenesis:
Absent organ despite presence of primordial tissue
What is hypoplasia?
Type of error in morphogenesis:
Incomplete organ development where the primordial tissue is present
What is Disruption?
Type of error in morphogenesis:
2o breakdown of previously normal tissue or structure (eg amniotic band syndrome)
What is Deformation?
Type of error in morphogenesis:
Extrinsic disruption; occurs after the embryonic period (weeks 3-8)
When is the embryonic period?
weeks 3-8
What is malformation?
Type of error in morphogenesis:
Intrinsic disruption; occurs during the embryonic period (weeks 3-8)
What is sequence?
Type of error in morphogenesis:
Abnormalities result from a single 1o embryolodic event (eg oligohydramnios -> Potter sequence)
Example of Disruption error in morphogenesis
Amniotic Band Syndrome
Example of Sequence error in morphogenesis
Oligohydramnios -> Potter sequence
When is the embryo most susceptible to teratogens?
Most susceptible 3-8 weeks (embryonic period - organogenesis)
Before week 3, “all-or-none” effects
After week 8, growth and function affected
Teratogen sensitivity before 3 weeks
Before week 3, “all-or-none” effects
Teratogen sensitivity after 8 weeks
After week 8, growth and function affected
Examples of classes of medications that are teratogenic
- ACE Inhibitors
- Alkylating agents
- Aminoglycosides
- Antiepileptic drugs
- Diethylstilbestrol
- Folate antagonists
- Isotretinoin
- Lithium
- Methimazole
- Tetracyclines
- Thalidomide
- Warfarin
Examples of substances that can be teratogenic in the setting of substance abuse
- Alcohol
- Cocaine
- Smoking (nicotine, CO)
Other teratogenic exposures
5 listed
- Iodine (lack or excess)
- Maternal diabetes
- Methylmercury
- Vitamin A excess
- X-rays
Ace inhibitors effects on fetus
Renal damage
Alkylating agents effects on fetus
- Absence of digits
- multiple anomalies
Aminoglycosides effects on fetus
Ototoxicity
Aminoglycosides = A mean guy hit the baby in the ear
Antiepileptic drugs effects on fetus
- Neural tube defects
- Cardiac defects
- cleft palate
- skeletal abnormalities (eg, phalanx/nail hypoplasia, facial dysmorphism)
High dose folate supplementation is recommended
Which antiepileptic drugs are most teratogenic?
Most commonly
- Valproate
- Carbamazapine
- Phenytoin
- Phenobarbital
Diethylstilbestrol effects on fetus
- Vaginal clear cell adenocarcinoma
- Congenital Müllerian anomalies
Folate antagonists effects on fetus
- Neural tube defects
- Includes Trimethoprim, methotrexate, antiepileptic drugs
Isotretinoin effects on fetus
- Multiple severe birth defects
- Contraception MANDATORY
- IsoTERATinoin
Lithium effects on fetus
Ebstein anomaly (apical displacement of the tricuspid valve)
What drug causes Ebstein anomaly
Lithium
What is Ebstein Anomaly?
Ebstein anomaly = apical displacement of tricuspid valve
Methimazole effects on fetus
Aplasia cutis congenita
Tetracyclines effects on fetus
- Discolored teeth
- Inhibited bone growth (teeth?)
Tetracyclines = “TEETHracyclines”
Thalidomide effects on fetus
- Limb defects (phocomelia, micromelia -“flipper” limbs)
Limb defects with “ tha-limb-domide”
Warfarin effects on fetus
- Bone deformities
- fetal hemorrhage
- abortion
- Ophthalmologic abnormalities
Do not wage Warfare on the baby; keep it heppy with heparin (does not cross the placenta)
Alcohol effects on fetus
- Common cause of birth defects and intellectual disability
- Fetal alcohol syndrome
Cocaine effects on fetus
- Low birth weight
- preterm birth
- IUGR
- placental abruption
Cocaine -> vasoconstriction
Smoking (nicotine and CO) effects on fetus
- Low birth weight (leading cause in developed countries)
- Preterm labor
- Placental problems
- IUGR
- SIDS
- ADHD
Nicotine -> vasoconstriction
CO -> impaired O2 delivery
What is the leading cause of low-brith-weight in developed countries?
Smoking
Iodine effects on fetus
Either from excess or lack of)
Congenital goiter (Excess)
hypothyroidism (Cretinism) (Lack)
Maternal Diabetes effects on fetus
- Caudal regression syndrome (anal atresia to sirenomelia)
- Congenital heart defects (eg VSD, transposition of the great vessels)
- Neural tube defects
- Macrosomia
- Neonatal hypoglycemia
- Polycythemia
Methylmercury effects on fetus
- Neurotoxicity
Highest in
- Swordfish
- Shark
- Tilefish
- King mackerel
Vitamin A excess effects on fetus
Extremely high risk for spontaneous abortions and birth defects (cleft palate, cardiac)
X-rays effects on fetus
- Microcephaly
- Intellectual disability
Minimized by lead shielding