Reproductive 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
Mutations in Sonic hedgehog gene
Can cause holoproscencephaly
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 craniocaudal direction.
Hox mutations result in..
appendages in wrong locations
Day 0 of fetal development
Fertilization by sperm forming zygote, initiating embryogenesis
Within week 1 of fertilization
hCG secretion begins after implantation of blastocyst
*pregnancy test can detect hCG levels within 7-11 days of fertilization
Within week 2 of fertilization
Bilaminar disc (epiblast, hypoblast)
2 weeks = 2 layers
Within week 3 of fertilization
Trilaminar disc. 3 weeks = 3 layers (ectoderm, mesoderm, endoderm)
Gastrulation
Primitive streak, notochord, mesoderm, and its organization and neural plate begin to form
Within weeks 3 - 8 of fertilization (embryonic period)
Neural tube formed by neuroectoderm and closes by week 4
Organogenesis
Extremely susceptible to teratogens
Within week 4 of fertilization
Heart begins to beat
Upper and lower limb buds begins to form
“4 weeks = 4 limbs”
Within week 8 (start of fetal period)
Fetal movement, fetus looks like a baby
Within 10 weeks of fertilization
Genitalia have male/female characteristics
Gastrulation
Process that forms the trilaminar embryonic disc. Establishes the ectoderm, mesoderm, and endoderm germ layers.
Starts with the epiblast invagination to form the primitive streak.
Three layers of ectoderm
Surface ectoderm
Neuroectoderm
Neural crest
Surface ectoderm derivatives
Adenohypophysis (from Rathke's pouch); lens of eye; epithelial linings of oral cavity; sensory organs of ear olfactory epithelium; epidermis; anal canal BELOW the pectinate line Parotid, sweat, and mammary glands
Derivatives of neuroectoderm
Brain (neurohypophysis) CNS neurons Oligodendrocytes Astrocytes Ependymal cells Pineal glands Retina and optic nerve Spinal cord
Neural crest derivatives
PNS (dorsal root ganglia, cranial nerves, celiac ganglion, Schwann cells, ANS) Melanocytes Chromafiin cells of adrenal medulla Parafollicular ("C") cells of thyroid Pia and arachnoid Bones of skull Odontoblasts Aorticopulmonary septum
Craniopharyngioma
benign Rathke’s pouch tumor with cholesterol crystals, calcifications
commonly seen in young children
Mesoderm derivatives
Muscle, bone, connective tissue
Seroud linings of body cavities (e.g. peritoneum)
Spleen (derived from foregut mesentary)
CV structures, lymphatics, blood
Wall of gut tube, wall of bladder, urethra, vagina, kidneys, adrenal cortex, dermis, testes, ovaries
Notochord induces ectoderm to form what structure?
Neuroectoderm (neural plate)
Postnatal derivative of the notochord
Nucleus pulposus of the intervertebral disc
Endoderm derivatives
Gut tube epithelium (including anal canal ABOVE the pectinate line) and luminal epithelial derivatives (e.g. lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroud, thyroid follicullar cells)
Mesodermal defects
VACTERL V-ertebral defects A-nal atresia C-ardiac defects T-racheo-Esophageal fistula R-enal defects L-imb defects (bone and muscle)
Endoderm
Agenesis
Agenesis
absent organ due to absent primordial 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)
Teratogens most susceptible during which period?
3rd - 8 weeks (organogenesis) of pregnancy
Effects of teratogen on pregnancy before week 3 of pregnancy
All or none effects
Teratogen effects after 8th weeks of pregnancy
Growth and function affected
ACE inhibitor effects on fetus
renal damage
Alkylating agents effects on fetus
Absence of digits, multiple anomalies
Aminoglycosides effect on fetus
CN VIII toxicity
Carbamazepine effects on fetus
Neural tube defects Craniofacial defects Fingernail hypoplasia Developmental delay IUGR
Diethylstilbestrol effects on fetus
Vaginal clear cell adenocarcinoma, congenital Mullerian anomalies
Folate antagonists’ effect on fetus
Neural tube defects
Lithium’s effect on fetus
Ebstein’s anomaly (atrialized right ventricle)
Phenytoin’s effect on fetus
Fetal hydantoin syndrome Microencephaly Dysmorphic craniofacial features Hypoplasit nails and distal phalanges Cardia defects IUGR mental retardation
Tetracyclines’ effect on fetus
Discolored teeth
Thalidomide’s effects on fetus
Limb defects (“flipper” limbs)
Valproate’s effects on fetus
Inhibition of maternal folate absorption –> neural tube defects
Warfarin’s effect on fetus
Bone deformities, fetal hemorrhage, abortion, opthalmologic abnormalities
*Use heparin as an alternative
Alcohol’s effect on fetus
Leading cause of birth defect and mental retardation; fetal alcohol syndrome
Cocaine’s effect on fetus
Abnormal fetal development and fetal addiction; placental abruption
Smoking’s effect on fetus (e.g. nicotine, CO)
Preterm labor, placental problems, IUGR, ADHD
Iodide (lack or excess) effect on fetus
Congenital goiter or cretinism
Maternal Diabetes’ effect on fetus
Caudal regression syndrome (anal atresia to sirenomelia)
Congenital heart defects
Neural tube defects
Transient HYPOglycemia due to fetal islet cell hyperplasia
Vitamin A (excess) effects on fetus
Extremely high risk for spontaneous abortion and birth defects (cleft palate, cardiac abnormalities)
X-rays’ effect on fetus
Microcephaly and mental retardation
Fetal alcohol syndrome
Leading cause of congenital malformations in the US
Increased incidence of congenital abnormalities, mental retardation, pre- and postnatal developmental retardation, microcephaly, holoproscencephaly, facial abnormalities, limb dislocation, and heart and lung fistulas
Dizygotic twins
arise from 2 eggs that are separately fertilized by 2 different sperm
(always 2 different zygotes) will have 2 separate amniotic sacs and 2 separate placentas
Monozygotic twins
arise from 1 fertilized egg (1 egg + 1 sperm) that splits into 2 zygotes early in the process
When does cleavage occur for most monozygotic twins?
4-8 days (after formation of morula)
- formation of monochorionic diamniotic
Zygote cleavage after 0-4 days occurs when
Dichorionic diamniotic (fused placenta or separate placenta)
Fertilized egg cleavage after 8-12 days (blastocyst stage) results in …
monochorionic diamniotic
Zygotic cleavage after embryonic disc formation (>13 days) results in …
monochorionic monoamniotic (conjoined twins)
Placenta
1st site of nutrient and gas exchange
Cytotrophoblast
inner layer of chorionic villi
Syncytotrophoblast
Outer blast of chorionic villi
secretes hCG (similar to LH)
stimulates corpus luteum to secrete progesterone during 1st trimester of pregnancy
Decidua basalis
derived from endometrium
maternal blood in lacunae
Umbilical arteries (2)
return deoxygenated blood from fetal internal iliac arteries to placenta
Umbilical VEIN - only ONE
supplies oxygenated blood from placenta to fetus; drains via ductus venosus into IVC
T/F. Single umbilical artery is phenotypically normal.
Single umbilical artery is associated with congenital and chromosomal arteries.
Umbilical arteries and veins are derived from….
Allantois
Urachal duct
formed in 3rd week
Yolk sac forms allantois, which extends into urogenital sinus. Allantois becomes urachus, a duct between bladder and yolk sac
Patent urachus
results in urine discharge from the umbilicus
Failure of urachus to obliterate:
Vesicourachal diverticulum – outpouching of the bladder
Vitelline duct
formed in 7th week - obliteration of vitelline duct (omphalo-mesenteric duct), which connects yolk sac to midgut lumen
Failure of vitteline duct to close results in these 2 conditions
Vitelline fistula
Meckel’s diverticulum
Vitelline fistula
results from vitelline duct failing to close:
meconium discharge from umbilicus
Meckel’s diverticulum
results from failure of vitelline duct to close
partial closure, with patent portion attached to ileum. May have ectopic gastric mucosa –> melena, periumbilical pain and ulcer
Aortic derivatives
6 of them. which develop in to the arterial system
1st aortic arch derivative
1st - part of maxillary artery (branch of external carotid)
“1st arch is MAXimal”
Second aortic arch
Stapedial artery and hyoid artery
“Second” = “S”tapedial
Third aortic arch derivative
Common carotid artery and proximal part of internal carotid artery
Fourth aortic arch
On left, aortic arch
On right - proximal part of internal Carotid artery
Sixth aortic arch
Proximal part of pulmonary arteries and (on left only) ductus arteriosus
6 arch = pulmonary and the pulmonary to systemic shunt (ductus arteriosus)
Branchial apparatus
Also called pharyngeal apparatus.
Composed of “CAP”
= clefts, arches, pouches
Brachial clefts derived from
ectoderm. Also called brachial grooves
Branchial arches derived from …
Mesoderm (muscles, arteries) and neural crest (bones, cartilage)
Branchial pouches derived from …
endoderm
1st branchial cleft derivative
external auditory meatus
2nd through 4th branchial cleft form….
temporary cervical sinuses, which are obliterated by proloferation of 2nd arch mesenchyme
Persistent cervical sinus leads too…
branchial cleft cyst within lateral neck
1st branch arch derivatives
Meckel’s cartilage (Mandible, Malleus, incus, sphenomandibular ligament)
Muscles of Mastication (Temporalis, Medial pterygoids, Masseter), Mylohyoid, anterior belly of digastric, tensor tympani, tensor veil palantini
Nerves: CN V2 and V3
Treacher Collins syndrome
1st arch neural crest fails to migrate –> mandibular hypoplasia, facial abnormalities
Second Branchial Arch: Cartilage
Reichert’s cartilage: Stapes, Styloid process, lesser horn of hyoid, Stylohyoid ligament
2nd branchial arch muscle derivatives
Muscles of facial expression: Stapedius, Stylohyoid, posterior belly of digastric
Second Branchial Arch: Nerve Derivatives
CN VII (facial expression)
Third Branchial Arch: Cartilage
Greater horn of hyoid
Third Branchial Arch Muscles
Stylopharngeaus (think stylopharyngeus innervated by glossopharyngeal nerve)
Third Branchial Arch Nerve Nerve Derivative
CN IX
Congenital pharyngocutaneous fistula
Persistence of cleft and pouch –> fistula between tonsillar area, cleft in lateral neck
4th and 4th arches: cartilage
Cartilage: thyroid, cricoid, arytenoids, corniculate, cuneiform
4th branchial arch muscles
most pharyngeal constrictors, cricothyroid, levator veli palantinin
6th arch muscle derivatives
all instrinsic muscles of larynx excpt cricothyroid
4th branchial arch nerve
CN X (superior laryngeal branch)
6th branchial arch nerves
CN X (recurrent laryngeal branch)
Arches 3 and 4 form
posterior 1/3 of tongue
Branchial arch 5 makes what developmental contributions
None
1st branchial pouch derivative
develops into middle ear cavity, eustachian tube, mastoid air cells
*1st pouch contributes to endoderm-lined structures of ear
2nd branchial pouch
develops into epithelial lining of palantine tonsil
3rd branchial pouch
dorsal wings - develops into inferior parathyroids
ventral wings - develops into thymus
3rd pouch contributes to which 3 structures?
Thymus, left and right inferior parathyroids
- 3rd pouch structures end up BELOW 4th pouch structures
Mneumonic for branchial pouch derivatives
"Ear, tonsils, bottom-to-top" 1-ear 2-tonsils 3-dorsal ("bottom" for inferior parathyroids) 3- ventral ("to "= thymus) 4- "top" = superior parathyroids
DiGeorge Syndrome
aberrant development of 3rd and 4th pouches –> T-cell deficiency (thymic aplasia) and hypocalcemia (failure of parathyroid development)
- deletion of chr 22 at q 11.2
MEN2A
Mutation 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
Cleft lip
failure of fusion of the maxillary and medial nasal processes (formation of primary palate)
Cleft palate
failure of fusion of the LATERAL palantine processes, the nasal septum and/or MEDIAN palantine process (formation of secondary palate)
- Cleft lip and cleft palate have two distinct etiologies, but often occur together
Female genital development
Default development. Mesonephrine duct degenerates and paramesonephric duct develops
Male genital development
SRY gene on Y chromosome - produces testis-determining factor (testes development)
Sertoli cells secrete Mullerian inhibitory factor (MID) that suppresses development of paramesonephric ducts
Leydig cells secrete androgens that stimulate the development of mesonephric ducts
Paramesoneprhic duct
develops into FEMALE internal structures - fallopian tubes, uterus, and upper portion of vagina (lower portion from urogenitl sinus)
Mullerian duct abnormalities result in anatomical defects that may present as primary amenorrhea in females with full developed secondary sexual characteristics (indicator of functional ovaries)
Mesonephric (Wolfian) duct
Develops into male internal structures (except prostate) - Seminal vesiscles, Epididymis, Ejaculatory duct, and Ductus deferens (SEED)
Result of no Sertoli cells or lack of MIF
Develop both male and female internal genitalia and male external genitalia
5-alpha reductase deficiency
Male internal genitalia, ambiguous external genitalia until puberty
Wolfian duct makes…
male internal genitalia EXCEPT prostate
Genital tubercle, urogenital sinus makes…
male external genitalia, prostate
Genital tubercle induced by dihydrotestosterone
Glans penis
Corpus cavernosum and spongiosum
Genital tubercle induced by estrogen
Glans clitoris, vestibular bulbs
Urogenital sinus induced by dihyrdotestosterone
Bulbourethral glands (of Cowper) Prostate gland
Urogenital sinus induced by estrogen
Greater vestibular glands (of Bartholin)
Urethral and paraurethral glands of Skene
Urogenital folds induced by dihydrotestosterone
Ventral shaft of penis (penile urethra)
Urogenital folds induced by estrogen
Labia minora
Labioscrotal swelling induced by dihydrotestosterone
Scrotum
Labioscrotal swelling induced by estrogen
Labia majora
Hypospadias
abnormal opening of penile urethra on inferior (ventral) side of penis due to failure of urethral folds to close
More common: hypospadias or epispadias?
Hypospadias. Must be fixed to prevent UTIs.
“Hypo” is below
Epispdias
abnormal opening on penile urethra on superior (dorsal) side of penis due to faulty positioning of genital tubercle
Extrophy of bladder is associated with what congenital penile abnormality?
Epispadas
“When you have Episadas, you hit your Eye when you pEE”
Gubernaculum (band of fibrous tissue)
in men: anchors testes within scrotum
in women: ovarian ligament + round ligament of uterus
Processus vaginalis (evagination) of peritoneum)
in women: forms tunica vaginalis
in men: obliterated
Gonadal venous drainage
left ovary/testis –> left gonadal vein –> left renal vein –> IVC
right ovary/testis –> right gonadal vein –> IVC
- similar to left adrenal vein drains to left renal vein before IVC
Gonadal lymphatic drainage
Ovaries/testes –> para-aortic lymph nodes
Distal 1/3 of vagina/vulva/scrotum –> superficial inguinal nodes
Proximal 2/3 of vagina/uterus –> obturator, external ilia and hypograstric nodes
Discuss difference in flow between left spermatic vein drainage and right spermatic draining.
Left spermatic vein enters the left renal vein at a 90 degress angle, flow is LESS continuous on left than on right.
- -> left venous pressure > right venous pressure
- -> variocele more common on left
Suspensory ligament of the ovaries
Connect ovaries to lateral pelvic wall
contains ovarian vessels
Structure at risk during ligation of ovarian vessels
Ureter
Cardinal ligament
connects cervix to sidewall of pelvis
contains uterine vessels
Structure at risk during ligation of uterine vessels in hysterectomy
Ureter
Round ligament of the uterus
connects uterine fundus to labia majora
structures contained artery of Sampson
Round ligament is derivative of ..
gubernaculum
Broad ligament
Connects uterine, fallopian tubes, and ovaries to pelvic side wall
Contains ovaries, fallopian tubes and round ligament of uterus
Components of broad ligament
Mesosalpinx, Mesometrium, and Mesovarium
Ligament of the ovary
Connects medial pole of ovary to lateral uterus
Vagina Histo
Stratified squamous epithelium, nonkeratinized
Ectocervix histology
Stratified squamous epithelium
Uterus histology
Simple columnar epithelium, pseudostratified tubular glands
Fallopian tube histology
Simple columnar epithelium, cilitated
Ovary histology
Simple cuboidal epithelium
Endocervix Histology
Simple columnar epithelium
Pathway of sperm during ejaculation
SEVEN UP Seminiferous tubules Epididymis Vas deferens Ejaculatory ducts Nothing Urethra Penis
Erection
Parasympathetic nervous system (pelvic nerve)
G protein pathway for NO
erection
NO –> increased cGMP –> smooth muscle relaxation –> vasodilation –> proerectile
G protein pathway for NE (antierection)
NE –> increased Ca –> smooth muscle contraction –> vasoconstriction –> antierectile
Emission
Sympathetic nervous system (hypogastric nerve)
Ejaculation
visceral and somatic nerves (pudendal nerve)
Mechanism of Sildenafil and Vardenafil
Inhibit cGMP breakdown
Cells in seminiferous tubules
Spermatagonia (germ cells) Sertoli cells (non-germ cells) Leydig cells (endocrine cells)
Spermatogonia
maintain germ pool and produce primary spermatocytes
Line seminiferous tubules
Sertoli cells (non-germ cells)
Secrete inhibin
Secrete androgen-binding protein (ABP)
Tight junction between adjacent Sertoli cells from blood-testis barrier
Support and nourish developing spermatozoa
Regulate spermatogenesis
Produce anti-mullerian hormone
Temperature sensitive ( decrease sperm production and decrease inhibin with increased temperature)`
Temperature in varicocele, cryptorchidism
Increased temperature
Leydig cells (endocrine cells)
secrete testosterone; testosterone production unaffected by temperature
Interstitium
Spermatogenesis
Spermatogenesis begins at puberty with spermatogonia Full development takes 2 months. Occurs in seminiferous tubes. Produces spermatids that undergo spermiogenesis (loss of cytoplasm contents, gain of acrosomal cap) to form mature spermatozoan
Spermatogonium
Diploid (2N, 2C)
Primary spermatocyte
Diploid (2N, 2C)
Secondary spermatocyte
Haploid (1N, 2C)
Spermatid
Haploid (1N, 1C)
Mature spermatozoon
Haploid (N)
LH
stimulates synthesis of testerone in Leydig cells
FSH
stimulates Sertoli cells to produce ABP and inhibin
Source of DHT and testosterone
testis
Source of androstendone
adrenal glands
Testosterone
Differentiation of epididymis, vas deferns, seminal vesicles (internal genitalia except prostate)
Growth spurt (penis, seminal vesicles, sperm, muscle, RBCs)
Deepening of voice
Closing of epiphyseal plates via estrogen converted from testosterone
Potency:
DHT, Androstenedione, testosterone
DHT > testosterone > androstenedione
Converts DHT to testosterone
5-alpha reductase (inhibited by finasteride)
Converts testosterone and androstenedione
Aromatase - converted in adipose tissue and Leydig cells
Aromatase
converts testosterone and androstenedione
Converts androgens to estrogen