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,HIGH-YIELD SYSTEMS
Reproductive
“Artificial insemination is when the farmer does it to the cow instead of the ` Embryology 612
bull.”
—Student essay ` Anatomy 624
Make no mistake about why these babies are here - they are here to ` Physiology 629
replace us.
—Jerry Seinfeld ` Pathology 638
“Whoever called it necking was a poor judge of anatomy.” ` Pharmacology 655
—Groucho Marx
“See, the problem is that God gives men a brain and a penis, and only
enough blood to run one at a time.”
—Robin Williams
The reproductive system can be intimidating at first but is manageable
once you organize the concepts into the pregnancy, endocrinologic,
embryologic, and oncologic aspects of reproduction. Study the
endocrine and reproductive chapters together, because mastery of
the hypothalamic-pituitary-gonadal axis is key to answering questions
on ovulation, menstruation, disorders of sexual development,
contraception, and many pathologies.
Embryology is a nuanced subject that covers multiple organ systems.
Approaching it from a clinical perspective will allow for better
understanding. For instance, make the connection between the
presentation of DiGeorge syndrome and the 3rd/4th pharyngeal pouch,
and between the Müllerian/Wolffian systems and disorders of sexual
development.
As for oncology, don’t worry about remembering screening or treatment
guidelines. It is more important to know how these cancers present (eg,
signs and symptoms) and their associated labs, histopathology, and risk
factors. In addition, some of the testicular and ovarian cancers have
distinct patterns of hCG, AFP, LH, or FSH derangements that serve as
helpful clues in exam questions.
611
,612 SEC TION III REPRODUC TIVE `R̀EPRODUCTIVE—EMBRYOLOGY
``
REPRODUCTIVE—EMBRYOLOGY
Important genes of embryogenesis
GENE LOCATION FUNCTION NOTES
Sonic hedgehog (SHH) Zone of polarizing activity at Anterior-posterior axis Mutations holoprosencephaly
gene base of limb buds patterning, CNS development
Wnt-7 gene Apical ectodermal ridge at Dorsal-ventral axis patterning,
distal end of each limb limb development
Fibroblast growth Apical ectodermal ridge Limb lengthening (via mitosis of “Look at that Fetus, Growing
factor (FGF) gene mesoderm) Fingers”
Homeobox (Hox) Multiple Segmental organization in Mutations appendages in
genes cranial-caudal direction, wrong locations. Isotretinoin
transcription factor coding Hox gene expression
Early fetal development
Early embryonic N = # of chromosomes
development C = # of chromatids/DNA copies
DAY 1 DAYS 2-3
Zygote
(2N4C)
DAY 4
Morula
Fertilization
(2N2C) Corpus albicans DAY 5
DAY 0 Developing Blastocyst
follicle
Ovary DAYS 6–10
Implantation
Myometrium
Ovulation
2° oocyte Early corpus
(1N2C) luteum Endometrium
Within week 1 hCG secretion begins around the time of Blastocyst “sticks” at day 6.
implantation of blastocyst.
Within week 2 Bilaminar disc (epiblast, hypoblast). 2 weeks = 2 layers.
Within week 3 Gastrulation forms trilaminar embryonic disc. 3 weeks = 3 layers.
Cells from epiblast invaginate primitive
streak endoderm, mesoderm, ectoderm.
Notochord arises from midline mesoderm;
overlying ectoderm becomes neural plate.
Weeks 3–8 Neural tube formed by neuroectoderm and Extremely susceptible to teratogens.
(embryonic period) closes by week 4.
Organogenesis.
Week 4 Heart begins to beat. 4 weeks = 4 limbs and 4 heart chambers.
Upper and lower limb buds begin to form.
Week 6 Fetal cardiac activity visible by transvaginal
ultrasound.
Week 8 Fetal movements start. Gait at week 8.
Week 10 Genitalia have male/female characteristics. Tenitalia.
, REPRODUC TIVE `R̀EPRODUCTIVE—EMBRYOLOGY SEC TION III 613
Embryologic derivatives
Ectoderm External/outer layer
Surface ectoderm Epidermis; adenohypophysis (from Rathke Craniopharyngioma—benign Rathke pouch
pouch); lens of eye; epithelial linings of oral tumor with cholesterol crystals, calcifications.
cavity, sensory organs of ear, and olfactory
epithelium; anal canal below the pectinate line;
parotid, sweat, mammary glands.
Neural tube Brain (neurohypophysis, CNS neurons, oligo- Neuroectoderm—think CNS.
dendrocytes, astrocytes, ependymal cells, pineal
gland), retina, spinal cord.
Neural crest Melanocytes, Odontoblasts, Tracheal cartilage, MOTEL PASSES
Enterochromaffin cells, Leptomeninges Neural crest—think PNS and non-neural
(arachnoid, pia), PNS ganglia (cranial, dorsal structures nearby.
root, autonomic), Adrenal medulla, Schwann
cells, Spiral membrane (aorticopulmonary
septum), Endocardial cushions (also derived
partially from mesoderm), Skull bones.
Mesoderm Muscle, bone, connective tissue, serous Middle/“meat” layer.
linings of body cavities (eg, peritoneum, Mesodermal defects = VACTERL:
pericardium, pleura), spleen (develops within Vertebral defects
foregut mesentery), cardiovascular structures, Anal atresia
lymphatics, blood, wall of gut tube, upper Cardiac defects
vagina, kidneys, adrenal cortex, dermis, testes, Tracheo-Esophageal fistula
ovaries, microglia. Renal defects
Notochord induces ectoderm to form Limb defects (bone and muscle)
neuroectoderm (neural plate); its only
postnatal derivative is the nucleus pulposus of
the intervertebral disc.
Endoderm Gut tube epithelium (including anal canal “Enternal” layer.
above the pectinate line), most of urethra and
lower vagina (derived from urogenital sinus),
luminal epithelial derivatives (eg, lungs,
liver, gallbladder, pancreas, eustachian tube,
thymus, parathyroid, thyroid follicular and
parafollicular [C] cells).
Types of errors in morphogenesis
Agenesis Absent organ due to absent primordial tissue.
Aplasia Absent organ despite presence of primordial tissue.
Hypoplasia Incomplete organ development; primordial tissue present.
Disruption 2° breakdown of previously normal tissue or structure (eg, amniotic band syndrome).
Deformation Extrinsic disruption (eg, multiple gestations crowding foot deformities); occurs after
embryonic period.
Malformation Intrinsic disruption; occurs during embryonic period (weeks 3–8).
Sequence Abnormalities result from a single 1° embryologic event (eg, oligohydramnios Potter sequence).
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