Reproductive - First Aid Flashcards
Important Genes of Embryogenesis:
- produced at base of limbs in zone of polarizing activity
- involved in patterning along anteroposterior axis and CNS development
- mutation can cause holoprosencephaly
Sonic Hedgehog Gene
Important Genes of Embryogenesis:
- produced at apical ectodermal ridge (thickened ectoderm at distal end of each developing limb)
- necessary for proper organization along dorsal-ventral axis
Wnt-7 Gene
Important Genes of Embryogenesis:
- produced at apical ectodermal ridge
- stimulates mitosis of underlying mesoderm, providing for lengthening of limbs
Fibroblast Growth Factor (FGF) Gene
“Look at that Fetus, Growing Fingers.”
Important Genes of Embryogenesis:
- involved in segmental organization of embryo in a craniocaudal direction
- code for transcription factors
- mutations → appendages in wrong locations
Homeobox (Hox) Genes
Early Embryonic Development
Early Fetal Development:
hCG secretion begins around the time of implantation of blastocyst
Week 1
Blastocyst “sticks” at day 6.
Early Fetal Development:
bilaminar disc (epiblast, hypoblast)
Week 2
2 weeks = 2 layers
Early Fetal Development:
- gastrulation forms trilaminar embryonic disc
- cells from epiblast invaginate → primitive streak → endoderm, mesoderm, ectoderm
- notochord arises from midline mesoderm
- overlying ectoderm becomes neural plate
Week 3
3 weeks = 3 layers
Early Fetal Development:
- neural tube formed by neuroectoderm and closes by week 4
- organogenesis
- extremely susceptible to teratogens
Weeks 3–8
(Embryonic Period)
Early Fetal Development:
- heart begins to beat
- upper and lower limb buds begin to form
Week 4
4 weeks = 4 limbs and 4 heart chambers
Early Fetal Development:
fetal cardiac activity visible by transvaginal ultrasound
Week 6
Early Fetal Development:
fetal movements start
Week 8
Gait at week 8.
Early Fetal Development:
genitalia have male/female characteristics
Week 10
tenitalia
Embryologic Derivatives:
external/outer layer
Ectoderm
Ectoderm:
- epidermis
- adenohypophysis (from Rathke pouch)
- lens of eye
- epithelial linings of oral cavity, sensory organs of ear, and olfactory epithelium
- anal canal below the pectinate line
- parotid, sweat, and mammary glands
- Craniopharyngioma
- benign Rathke pouch tumor with cholesterol crystals, calcifications
Surface Ectoderm
Ectoderm:
- brain (neurohypophysis, CNS neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland)
- retina
- spinal cord
Neural Tube
Ectoderm:
- melanocytes
- myenteric (Auerbach) plexus
- odontoblasts
- endocardial cushions
- laryngeal cartilage
- parafollicular 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
Neural Crest
MMOtEL PPASS:
- Melanocytes
- Myenteric (Auerbach) plexus
- Odontoblasts
- Endocardial cushions
- Laryngeal cartilage
- Parafollicular cells of the thyroid
- PNS (dorsal root ganglia, cranial nerves, autonomic ganglia)
- Adrenal medulla and all ganglia
- Spiral membrane (aorticopulmonary septum)
- Schwann cells
Embryologic Derivatives:
- muscle, bone, connective tissue, serous linings of body cavities (eg. peritoneum, pericardium, pleura), spleen (derived from foregut mesentery), cardiovascular structures, lymphatics, blood, wall of gut tube, upper 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
Mesoderm
middle/“meat” layer
Mesodermal Defects = VACTERL:
- Vertebral defects
- Anal atresia
- Cardiac defects
- Tracheo-Esophageal fistula
- Renal defects
- Limb defects (bone and muscle)
Embryologic Derivatives:
- gut tube epithelium (including anal canal 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 cells)
Endoderm
Types of Errors in Morphogenesis:
absent organ due to absent primordial tissue
Agenesis
Types of Errors in Morphogenesis:
absent organ despite presence of primordial tissue
Aplasia
Types of Errors in Morphogenesis:
- incomplete organ development
- primordial tissue present
Hypoplasia
Types of Errors in Morphogenesis:
2° breakdown of previously normal tissue or structure (eg. amniotic band syndrome)
Disruption
Types of Errors in Morphogenesis:
- extrinsic disruption
- occurs after embryonic period
Deformation
Types of Errors in Morphogenesis:
- intrinsic disruption
- occurs during embryonic period (weeks 3–8)
Malformation
Types of Errors in Morphogenesis:
abnormalities result from a single 1° embryologic event (eg. oligohydramnios → Potter sequence)
Sequence
_____ are agents or factors that causes malformation of an embryo. 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.
Teratogens
Teratogens:
- medication
- renal damage
ACE inhibitors
Teratogens:
- medication
- absence of digits
- multiple anomalies
Alkylating Agents
Teratogens:
- medication
- ototoxicity
Aminoglycosides
A mean guy hit the baby in the ear.
Teratogens:
- medication
- neural tube defects, cardiac defects, cleft palate, skeletal abnormalities (eg. phalanx/nail hypoplasia, facial dysmorphism)
- high-dose folate supplementation recommended
Antiepileptic Drugs
- Valproate
- Carbamazepine
- Phenytoin
- Phenobarbital
Teratogens:
- medication
- vaginal clear cell adenocarcinoma, congenital
- Müllerian anomalies
Diethylstilbestrol
Teratogens:
- medication
- neural tube defects
Folate Antagonists
- Trimethoprim
- Methotrexate
- Antiepileptic Drugs
Teratogens:
- medication
- multiple severe birth defects
- contraception mandatory
Isotretinoin
Teratogens:
- medication
- Ebstein anomaly (apical displacement of tricuspid valve)
Lithium
Teratogens:
- medication
- aplasia cutis congenita
Methimazole
Teratogens:
- medication
- discolored teeth
- inhibited bone growth
Tetracyclines
Teethracyclines
Teratogens:
- medication
- limb defects (phocomelia, micromelia—“flipper” limbs)
Thalidomide
Tha-limb-domide
Teratogens:
- medication
- bone deformities
- fetal hemorrhage
- abortion
- ophthalmologic abnormalities
Warfarin
Do not wage warfare on the baby; keep it heppy with heparin (does not cross placenta).
Teratogens:
- substance abuse
- common cause of birth defects and intellectual disability
- fetal _____ syndrome
Alcohol
Teratogens:
- substance abuse
- low birth weight
- preterm birth
- IUGR
- placental abruption
- vasoconstriction
Cocaine
Teratogens:
- substance abuse
- low birth weight (leading cause in developed countries)
- preterm labor
- placental problems
- IUGR, SIDS, ADHD
- vasoconstriction
- impaired O2 delivery
Smoking
- Nicotine → vasoconstriction
- CO → impaired O2 delivery
Teratogens:
- congenital goiter
- hypothyroidism (cretinism)
Iodine (lack or excess)
Teratogens:
- Caudal Regression Syndrome
- anal atresia to sirenomelia
- congenital heart defects (eg. VSD, transposition of the great vessels)
- neural tube defects, macrosomia, neonatal hypoglycemia, polycythemia
Maternal Diabetes
Teratogens:
- neurotoxicity
- highest in swordfish, shark, tilefish, and king mackerel
Methylmercury
Teratogens:
- spontaneous abortions
- birth defects (cleft palate, cardiac)
Vitamin A Excess
Teratogens:
- microcephaly
- intellectual disability
- minimized by lead shielding
X-rays
Teratogens:
- leading cause of intellectual disability in the US
- ↑ incidence of congenital abnormalities, including pre- and postnatal developmental retardation, microcephaly, facial abnormalities (eg. smooth philtrum, thin vermillion border [upper lip], small palpebral fissures), limb dislocation, and heart defects
- heart-lung fistulas and holoprosencephaly in most severe form
- mechanism is failure of cell migration
Fetal Alcohol Syndrome
Teratogens:
- complex disorder involving CNS, ANS, and GI systems
- secondary to maternal opiate use/abuse
- risk factors for maternal substance abuse during pregnancy include poor mental health, poor prenatal care, low SES, lack of family support, and HCV
- universal screening for substance abuse is recommended in all pregnant patients
- newborns may present with uncoordinated sucking reflexes, irritability, high-pitched crying, tremors, tachypnea, sneezing, diarrhea, and possibly seizures
Neonatal Abstinence Syndrome
Twinning
- Dizygotic (“fraternal”) twins arise from 2 eggs that are separately fertilized by 2 different sperm (always 2 zygotes) and will have 2 separate amniotic sacs and 2 separate placentas (chorions).
- Monozygotic (“identical”) twins arise from 1 fertilized egg (1 egg + 1 sperm) that splits in early pregnancy.
- The timing of cleavage determines chorionicity (number of chorions) and amnionicity (number of amnions) (SCAB):
- 0–4 days: Separate chorion and amnion
- 4–8 days: shared Chorion
- 8–12 days: shared Amnion
- 13+ days: shared Body (conjoined)
Placenta
1º site of nutrient and gas exchange between mother and fetus
Placenta
- fetal component
- inner layer of chorionic villi
Cytotrophoblast
Cytotrophoblast makes cells
Placenta
- fetal component
- outer layer of chorionic villi
- synthesizes and secretes hormones, eg. hCG (structurally similar to LH; stimulates corpus luteum to secrete progesterone during first trimester)
- lacks MHC-I expression → ↓chance of attack by maternal immune system
Syncytiotrophoblast
Syncytiotrophoblast synthesizes hormones
Placenta:
- maternal component
- derived from endometrium
- maternal blood in lacunae
Decidua Basalis
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 anomalies.
- 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 umbilicus.
- Failure of urachus to involute can lead to anomalies that may increase risk of infection and/or malignancy (eg. adenocarcinoma) if not treated.
- Obliterated urachus is represented by the median umbilical ligament after birth, which is covered by median umbilical fold of the peritoneum.
Urachus:
total failure of urachus to obliterate → urine discharge from umbilicus
Patent Urachus
Urachus:
- partial failure of urachus to obliterate
- fluid-filled cavity lined with uroepithelium, between umbilicus and bladder
- cyst can become infected and present as painful mass below umbilicus
Urachal Cyst
Urachus:
slight failure of urachus to obliterate → outpouching of bladder
Vesicourachal Diverticulum
Vitelline Duct
- connects yolk sac to midgut lumen
- 7th week—obliteration of vitelline duct (omphalomesenteric duct)
Vitelline Duct:
vitelline duct fails to close → meconium discharge from umbilicus
Vitelline Fistula
Vitelline Duct:
- partial closure of vitelline duct, with patent portion attached to ileum (true diverticulum)
- may have heterotopic gastric and/or pancreatic tissue → melena, hematochezia, abdominal pain
Meckel Diverticulum
Aortic Arch Derivatives
Develop into arterial system.
Aortic Arch Derivatives:
part of maxillary artery (branch of external carotid)
1st
1st arch is maximal
Aortic Arch Derivatives:
- stapedial artery
- hyoid artery
2nd
second = stapedial
Aortic Arch Derivatives:
- common carotid artery
- proximal part of internal Carotid artery
3rd
Carotid = C is the 3rd letter of alphabet
Aortic Arch Derivatives:
- left—aortic arch
- right—proximal part of right subclavian artery
4th
4th arch (4 limbs) = systemic
Aortic Arch Derivatives:
- proximal part of pulmonary arteries
- ductus arteriosus
6th
Branchial Apparatus
- Composed of branchial clefts, arches, and pouches.
-
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 + neural crest
- Pouches = endoderm
Branchial Cleft Derivatives:
develops into external auditory meatus
1st cleft
Branchial Cleft Derivatives:
form temporary cervical sinuses, which are obliterated by proliferation of 2nd arch mesenchyme
2nd through 4th clefts
Branchial Cleft Derivatives:
branchial cleft cyst within lateral neck, anterior to sternocleidomastoid muscle
Persistent Cervical Sinus
Branchial Arch Derivatives:
- Cartilage:
- maxillary process → maxilla, zygomatic bone
- mandibular process → Meckel cartilage, → mandible
- malleus and incus
- sphenomandibular ligament
- Muscles:
- muscles of mastication (temporalis, masseter, lateral and medial pterygoids)
- mylohyoid
- anterior belly of digastric
- tensor tympani
- anterior 2⁄3 of tongue
- tensor veli palatini
- Nerves:
- CN V3—chew
- Pierre Robin Sequence
- micrognathia, glossoptosis, cleft palate, airway obstruction
- Treacher Collins Syndrome
- neural crest dysfunction → mandibular hypoplasia, facial abnormalities
1st Branchial Arch
When at the restaurant of the golden arches, children tend to first chew (1), then smile (2), then swallow stylishly (3) or simply swallow (4), and then speak (6).
Branchial Arch Derivatives:
- Cartilage:
- Reichert Cartilage:
- stapes
- styloid process
- lesser horn of hyoid
- stylohyoid ligament
- Reichert Cartilage:
- Muscles:
- muscles of facial expression
- stapedius
- stylohyoid
- platysma
- posterior belly of digastric
- Nerves:
- CN VII—facial expression, smile
- Pierre Robin Sequence
- micrognathia, glossoptosis, cleft palate, airway obstruction
- Treacher Collins Syndrome
- neural crest dysfunction → mandibular hypoplasia, facial abnormalities
2nd Branchial Arch
When at the restaurant of the golden arches, children tend to first chew (1), then smile (2), then swallow stylishly (3) or simply swallow (4), and then speak (6).
Branchial Arch Derivatives:
- Cartilage:
- greater horn of hyoid
- Muscles:
- stylopharyngeus (innervated by
glossopharyngeal nerve)
- stylopharyngeus (innervated by
- Nerves:
- CN IX—stylopharyngeus, swallow
3rd Branchial Arch
When at the restaurant of the golden arches, children tend to first chew (1), then smile (2), then swallow stylishly (3) or simply swallow (4), and then speak (6).
Branchial Arch Derivatives:
- Cartilage:
- arytenoids
- cricoid
- corniculate
- cuneiform
- thyroid
- Muscles:
- most pharyngeal constrictors
- cricothyroid
- levator veli palatini
all intrinsic muscles of larynx except cricothyroid
- Nerves:
- CN X—superior laryngeal branch, swallow
- 6th arch: CN X—recurrent/inferior laryngeal branch, speak
4th–6th Branchial Arches
- 4th Arch
- most pharyngeal constrictors, cricothyroid, and levator veli palatini
- CN X—superior laryngeal branch, swallow
- 6th Arch
- all intrinsic muscles of larynx except cricothyroid
- CN X (recurrent/inferior laryngeal branch) speak
- Arches 3 and 4 form posterior 1⁄3 of tongue.
- Arch 5 makes no major developmental contributions.
Sing and ACCCT:
- Arytenoids
- Cricoid
- Corniculate
- Cuneiform
- Thyroid
When at the restaurant of the golden arches, children tend to first chew (1), then smile (2), then swallow stylishly (3) or simply swallow (4), and then speak (6).
Branchial Pouch Derivatives:
- middle ear cavity
- eustachian tube
- mastoid air cells
- contributes to endoderm-lined structures of ear
1st Branchial Pouch
ears, tonsils, bottom-to-top:
- 1 (ears)
- 2 (tonsils)
- 3 dorsal (bottom = inferior parathyroids)
- 3 ventral (to = thymus)
- 4 (top = superior parathyroids)
Branchial Pouch Derivatives:
epithelial lining of palatine tonsil
2nd Branchial Pouch
ears, tonsils, bottom-to-top:
- 1 (ears)
- 2 (tonsils)
- 3 dorsal (bottom = inferior parathyroids)
- 3 ventral (to = thymus)
- 4 (top = superior parathyroids)
Branchial Pouch Derivatives:
- dorsal wings → inferio parathyroids
- ventral wings → thymus
- contributes to 3 structures (thymus, left and right inferior parathyroids)
- end up below 4th-pouch structures
3rd Branchial Pouch
ears, tonsils, bottom-to-top:
- 1 (ears)
- 2 (tonsils)
- 3 dorsal (bottom = inferior parathyroids)
- 3 ventral (to = thymus)
- 4 (top = superior parathyroids)
Branchial Pouch Derivatives:
- dorsal wings → superior parathyroids
- ventral wings → ultimobranchial body → parafollicular cells of thyroid
4th Branchial Pouch
ears, tonsils, bottom-to-top:
- 1 (ears)
- 2 (tonsils)
- 3 dorsal (bottom = inferior parathyroids)
- 3 ventral (to = thymus)
- 4 (top = superior parathyroids)
Branchial Pouch:
- chromosome 22q11 deletion
- aberrant development of 3rd and 4th pouches → T-cell deficiency (thymic aplasia) and hypocalcemia (failure of parathyroid development)
- associated with cardiac defects (conotruncal anomalies)
DiGeorge Syndrome
Cleft Lip and Palate
- Cleft Lip
- failure of fusion of the maxillary an merged medial nasal processes (formation of 1° palate)
- Cleft Palate
- failure of fusion of the two lateral palatine shelves or failure of fusion of lateral palatine shelves with the nasal septum and/or median palatine shelf (formation of 2° palate)
- Cleft lip and cleft palate have distinct, multifactorial etiologies, but often occur together.
Genital Embryology:
Female
- default development
- mesonephric duct degenerates and paramesonephric duct develops
Genital Embryology:
Male
- SRY gene on Y chromosome—produces testis-determining factor → testes development
- Sertoli cells secrete Müllerian inhibitory factor (MIF) that suppresses development of paramesonephric ducts.
- Leydig cells secrete androgens that stimulate development of mesonephric ducts.
Genital Embryology:
Paramesonephric (Müllerian) Duct
- develops into female internal structures—fallopian tubes, uterus, upper portion of vagina (lower portion from urogenital sinus)
- male remnant is appendix testis
Genital Embryology:
may present as 1° amenorrhea (due to a lack of uterine development) in females with fully developed 2° sexual characteristics (functional ovaries)
Müllerian Agenesis
(Mayer-Rokitansky-Küster-Hauser syndrome)
Genital Embryology:
Mesonephric (Wolffian) Duct
- develops into male internal structures (except prostate)
-
SEED:
- Seminal vesicles
- Epididymis
- Ejaculatory duct
- Ductus deferens
-
SEED:
- female remnant is Gartner duct
Sexual Differentiation
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 ↑ testosterone levels cause masculinization)
In the testes:
- Leydig cells Leads to male (internal and external) sexual differentiation.
- Sertoli cells Shuts down female (internal) sexual differentiation.
Uterine (Müllerian Duct) Anomalies:
- common anomaly
- incomplete resorption of septum
- ↓ fertility and early miscarriage/pregnancy loss
- treated with septoplasty
Septate Uterus
Uterine (Müllerian Duct) Anomalies:
- incomplete fusion of Müllerian ducts
- ↑ risk of complicated pregnancy, early pregnancy loss, malpresentation, prematurity
Bicornuate Uterus
Uterine (Müllerian Duct) Anomalies:
- complete failure of fusion → double uterus, cervix, vagina
- pregnancy possible
Uterus Didelphys
Male/Female Genital Homologs
Congenital Penile Abnormalities:
- abnormal opening of penile urethra on ventral surface of penis due to failure of urethral folds to fuse
- more common than epispadias
- associated with inguinal hernia and cryptorchidism
Hypospadias
Congenital Penile Abnormalities:
- abnormal opening of penile urethra on dorsal surface of penis due to faulty positioning of genital tubercle
- associated with exstrophy of the bladder is
Epispadias
When you have Epispadias, you hit your Eye when you pEE.
Descent of Testes and Ovaries:
- band of fibrous tissue
- Male Remnant:
- anchors testes within scrotum
- Female Remnant:
- ovarian ligament + round ligament of uterus
Gubernaculum
Descent of Testes and Ovaries:
- evagination of peritoneum
- Male Remnant:
- forms tunica vaginalis
- Female Remnant:
- obliterated
Processus Vaginalis
Gonadal Venous Drainage
- right ovary/testis → right gonadal vein → IVC
- left ovary/testis → left gonadal vein → left renal vein → IVC
- “Left gonadal vein takes the Longest way.”
- Because the left spermatic vein enters the left renal vein at a 90° angle, flow is less laminar on left than on right → left venous pressure > right venous pressure → varicocele more common on the left.
Gonadal Lymphatic Drainage
- ovaries/testes → para-aortic lymph nodes
- body of uterus/superior bladder → external iliac nodes
- prostate/cervix/corpus cavernosum/proximal vagina → internal iliac nodes
- distal vagina/vulva/scrotum/distal anus → superficial inguinal nodes
- glans penis → deep inguinal nodes
Female Reproductive Anatomy
Female Reproductive Anatomy:
- connects ovaries to lateral pelvic wall
- contains ovarian vessels
- also called suspensory ligament of the ovary
- ligate vessels during oophorectomy to avoid bleeding
- ureter courses retroperitoneally, close to gonadal vessels → at risk of injury during ligation of ovarian vessels
Infundibulopelvic Ligament
Female Reproductive Anatomy:
- connects cervix to side wall of pelvis
- contains uterine vessels
- ureter at risk of injury during ligation of uterine vessels in hysterectomy
Cardinal ligament
Female Reproductive Anatomy:
- connects uterine horn to labia majora
- derivative of gubernaculum
- travels through round inguinal canal
- above the artery of Sampson
Round Ligament of the Uterus
Female Reproductive Anatomy:
- connects uterus, fallopian tubes, and ovaries to pelvic side wall
- contains ovaries, fallopian tubes, and round ligaments of uterus
- fold of peritoneum that comprises the mesosalpinx, mesometrium, and mesovarium
Broad Ligament
Female Reproductive Anatomy:
- medial pole of ovary to uterine horn
- derivative of gubernaculum
Ovarian Ligament
Ovarian Ligament Latches to Lateral uterus.
Female Reproductive Epithelial Histology:
Vagina
nonkeratinized stratified squamous epithelium
Female Reproductive Epithelial Histology:
Ectocervix
nonkeratinized stratified squamous epithelium
Female Reproductive Epithelial Histology:
Transformation Zone
squamocolumnar junction
- most common area for cervical cancer
Female Reproductive Epithelial Histology:
Endocervix
simple columnar epithelium
Female Reproductive Epithelial Histology:
Uterus
simple columnar epithelium
- proliferative phase—long tubular glands
- secretory phase—coiled glands
Female Reproductive Epithelial Histology:
Fallopian Tube
ciliated simple columnar epithelium
Female Reproductive Epithelial Histology:
outer surface of the ovaries
simple cuboidal epithelium
- germinal epithelium covering surface of ovary
Male Reproductive Anatomy
Pathway of Sperm during Ejaculation—SEVEN UP:
- Seminiferous tubules
- Epididymis
- Vas deferens
- Ejaculatory ducts
- (Nothing)
- Urethra
- Penis