Reproduction Flashcards
Sonic Hedgehog Gene
Produced at base of limbs in zone of polarizing activity
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 (like Wnt-7).
Stimulates mitosis of underlying mesoderm, providing for lengthening of limbs
Homeobox (Hox) genes
Involved in segmental organization of embryo in a craniocaudal direction.
Code for transcription factors.
Hox mutations lead to appendages in wrong locations
Early Fetal development (through week 10)
Day 0 - Fertilization by sperm, forming zygote, initiating embryogenesis.
Within week 1 - hCG secretion begins around the time of implantation of blastocyst (it “sticks” at day 6)
Within week 2 - Bilaminar disc (epiblast, hypoblast). 2 weeks = 2 layers
Within week 3 - Trilaminiar disc. 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 US
Week 10 - Genitalia have male/female characteristics
Gastrulation
Within week 3
Process that forms the trilaminar embryonic disc. Establishes the ectoderm, mesoderm, and endoderm germ layers.
Starts with epiblast invaginating to form the primitive streak.
Ectoderm
External/outer layer
1) Surface Ectoderm - Epidermis; adenohypophysis (from Rathke pouch); lens of eye; epithelial linings of oral cavity, sensory organs of ear, and olfactor epithelium; epidermis; anal canal below the pectinate line; parotid, sweat, and mammary glands
Craniopharyngioma - benign Rathke pouch tumor with cholesterol crystals, calcifications
2) Neuroectoderm - Brain (neurohypophysis, CNS, neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland), retina and optic nerve, spinal cord
3) Neural crest - PNS (dorsal root ganglia, cranial nerves, celiac ganglion, Schwann cells, ANS), melanocytes, chromaffin cells of adrenal medulla, parafollicular (C) cells of thyroid, pia, and arachnoid, bones of the skull, odontoblasts, aorticopulmonary septum
Mesoderm
Middle/”Meat” layer
Muscle, bone, connective tissue, serous linings of body cavities (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
V = vertebral defects A = Anal atresia C = Cardiac defects T/E = Tracheo-Esophageal fistula R = Renal defects L = Limb defects (bone and muscle)
Endoderm
Gut tube epithelium (including anal canal above the pectinate line), most of urethra (derived from urogenital sinus), luminal epithelial derivatives (lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular cells)
Organ morphogenesis errors
1) Agenesis - absent organ bc of absent primordial tissue
2) Aplasia - absent organ despite presence of primordial tissue
3) Hypoplasia - Incomplete organ development; primordial tissue present
4) Deformation - Extrinsic disruption; occurs after embryonic period
5) Disruption - Secondary breakdown of previously normal tissue or structure (e.g. amniotic band syndrome)
6) Malformation - Intrinsic disruption; occurs during embryonic period (wks 3-8)
7) Sequence - Abnormalities result from single primary embryologic event (e.g. oligohydramnios leading to Potter Sequence)
Teratogens
Most susceptible in wks 3-8 of pregnancy. Before week 3, “all or none” effects. After week 8, growth and function affected.
Medications that are teratogens
1) ACE Inhibitors - Renal damage
2) Alkylating agents - Absence of digits, multiple anomalies
3) Aminoglycosides - CN8 toxicity
4) Carbamazepine - Facial dysmorphism, developmental delay, neural tube defects, phalanx/fingernail hypoplasia
5) Diethylstilbestrol (DES) - Vaginal clear cell adenocarcinoma, congenital Mullerian anomalies
6) Folate antagonists - Neural tube defects
7) Isotretinoin - Multiple severe birth defects (contraception mandatory)
8) Lithium - Ebstein anomaly (atrialized RV)
9) Methimazole - Aplasia cutis congenita
10) Phenytoin - Fetal hydantoin syndrome - cleft palate, cardiac defects, phalanx/fingernail hypoplasia
11) Tetracyclines - Discolored teeth
12) Thalidomide - Limb defects (phocomelia, micromelia - flipper limbs)
13) Valproate - Inhibition of maternal folate absorption leads to neural tube defects
14) Warfarin - Bone deformities, fetal hemorrhage, abortion, ophthalmologic abnormalities (Use heparin - doesn’t cross placenta)
Substance abuse/teratogens
1) Alcohol - Common cause of birth defects and intellectual disability; fetal alcohol syndrome
2) Cocaine - Abnormal fetal growth and fetal addiction; placental abruption
3) Smoking (Nicotine, CO) - Low birth weight (leading cause in developed countries), preterm labor, placental problems, IUGR, ADHD - Nicotine leads to vasoconstriction. CO leads to impaired O2 delivery
Other teratogens
1) Iodine (lack or excess) - Congenital goiter or hypothyroidism (cretinism)
2) Maternal diabetes - Caudal regression syndrome (anal atresia to sirenomelia), congenital heart defects, neural tube defects
3) Vitamin A (excess) - Extremely high risk for spontaneous abortions and birth defects (cleft palate, cardiac)
4) X-Rays - Microcephaly, intellectual disability - minimized by lead shielding
Fetal Alcohol Syndrome
Leading cause of intellectual disability in the US.
Newborns of alcohol-consuming mothers have higher incidence of congenital abnormalities, including pre and postnatal developmental retardation, microcephaly, facial abnormalities (smooth philtrum, hypertelorism), limb dislocation, heart defects.
Heat-lung fistulas and holoprosencephaly in most severe form. Mechanism is failure of cell migration.
Placenta
Primary site of nutrient and gas exchange between mother and fetus
Fetal component
1) Cytotrophoblast - inner layer of chorionic villi. Cytotrophoblast makes Cells.
2) Syncytiotrophoblast - Outer layer of chorionic villi; secretes hCG (structurally similar to LH; stimulates corpus luteum to secrete progesterone during first trimester)
Lacks MHC-1 expression leading to lower chance of attack by maternal immune system
Maternal component
1) Decidua basalis - Derived from endometrium. Maternal blood in lacunae
Umbilical cord
Umbilical arteries (2) - return deoxygenated blood from fetal internal iliac arteries to placenta
Umbilical vein (1) - supplies oxygenated blood from placenta to fetus; drains into IVC via liver or via ductus venosus
Single umbilical artery (2 vessel cord) is associated with congenital and chromosomal abnormalities
Umbilical arteries and vein are derived from allantois
Urachus
In the 3rd week the yolk sac forms the allantois, which extends into urogenital sinus. Allantois becomes the urachus, a duct between fetal bladder and yolk sac.
Patent Urachus - total failure to obliterate leads to 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 - Slight failure to obliterate leads to outpouching of bladder
Vitelline duct
7th week - obliteration of vitelline duct (omphalo-mesenteric duct), which connects yolk sac to midgut lumen
Vitelline fistula - vitelline duct fails to close leading to meconium discharge from umbilicus
Mechel diverticulum - partial closure of vitelline duct, with patent portion attached to ileum (true diverticulum). May have heterotopic gastric and/or pancreatic tissue causing melena, hematochezia, abdominal pain.
Aortic arch derivatives
Develop into arterial system
1) Part of maxillary artery (branch of external carotid)
2) Stapedial artery and hyoid artery (Second = Stapedial)
3) Common Carotid artery and proximal part of internal Carotid artery (C is 3rd letter)
4) On left, aortic arch; On right, proximal part of R Subclavian artery
6) Proximal part of pulmonary arteries and (on left only) ductus arteriosis)
Branchial apparatus
Also called pharyngeal apparatus. Composed of branchial clefts, arches, pouches
Brancial clefts = derived from ectoderm. Also called grooves
Arches = derived from mesoderm (muscles, arteries) and neural crest (bones, cartilage)
Pouches = derived from endoderm
Branchial cleft derivatives
1st cleft = external auditory meatus
2-4 = temporary cervical sinuses, which are obliterated by proliferation of 2nd arch mesenchyme
Persistent cervical sinus leads to branchial cleft cyst within lateral neck
1st Branchial Arch
Mechel cartilage: Mandible, Malleus, incus, spheno-Mandibular ligament
Muscles of Mastication (temporalis, Masseter, lateral, and Medial pterygoids), Mylohyoid, anterior belly of digastric, tensor tympani, tensor veli palatini
CN V2 and V3 (chew)
Treacher Collins Syndrome - 1st arch neural crest fails to migrate leading to mandibular hypoplasia, facial abnormalities
2nd Branchial Arch
Reichert cartilage: Stapes, Styloid process, lesser horn of hyoid, Stylohyoid ligament
Muscles of facial expression, Stapedius, Stylohyoid, platySma, posterior belly of digastric
CN VII (facial expression - smile)
Congenital Pharyngocutaneous fistula - persistence of cleft and pouch leads to fistula between tonsilar area and lateral neck