Reproductive- Embryology Flashcards
Important genes of embryogenesis
- Sonic hedgehog gene
Produced at base of limbs in zone of polarizing activity. Involved in patterning along anteroposterior axis and CNS development;
mutation can cause holoprosencephaly
Important genes of embryogenesis
- 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.
Important genes of embryogenesis
- Fibroblast growth factor (FGF) gene
Produced at apical ectodermal ridge.
Stimulates mitosis of underlying mesoderm, providing for lengthening of limbs.
“Look at that Fetus, Growing Fingers.”
Important genes of embryogenesis
- Homeobox (Hox) genes
Involved in segmental organization of embryo in a craniocaudal direction. Code for transcription factors.
Hox mutations appendages in wrong locations.
Early fetal development
- Within week 1
- Within week 2
- Within week 3
hCG secretion begins around the time of implantation of blastocyst
Bilaminar disc (epiblast, hypoblast).
Gastrulation forms trilaminar embryonic disc. Notochord arises from midline mesoderm; overlying ectoderm becomes neural plate.
Early fetal development
- Weeks 3–8 (embryonic period)
Neural tube formed by neuroectoderm and closes by week 4. Organogenesis.
Early fetal development
- Week 4
- Week 6
- Week 8
- Week 10
Heart begins to beat. Upper and lower limb buds begin to form.
Fetal cardiac activity visible by transvaginal ultrasound
Fetal movements start.
Genitalia have male/female characteristics
Mesodermal defects = VACTERL
Vertebral defects Anal atresia Cardiac defects Tracheo-Esophageal fistula Renal defects Limb defects (bone and muscle)
Embryologic derivatives
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Types of errors in morphogenesis
- Agenesis
- Aplasia
- Hypoplasia
- Deformation
Absent organ due to absent primordial tissue.
Absent organ despite presence of primordial tissue
Incomplete organ development; primordial tissue present.
Extrinsic disruption; occurs after embryonic period.
Types of errors in morphogenesis
- Disruption
- Malformation
- Sequence
2° breakdown of previously normal tissue or structure (eg, amniotic band syndrome).
Intrinsic disruption; occurs during embryonic period (weeks 3–8).
Abnormalities result from a single 1° embryologic event (eg, oligohydramnios Potter sequence).
Teratogens
Most susceptible in 3rd–8th weeks of pregnancy.
Before week 3, “all-or-none” effects. After week 8, growth and function affected.
Teratogens medications - ACE inhibitors - Alkylating agents - Aminoglycosides - Folate antagonists (trimethoprim, methotrexate, antiepileptic)
Renal damage
Absence of digits, multiple anomalies
Ototoxicity
Neural tube defects
Teratogens medications
- Antiepileptic drugs
- Diethylstilbestrol
Neural tube defects, cardiac defects, cleft palate, skeletal abnormalities. (valproate, carbamazepine, phenytoin, phenobarbital)
Vaginal clear cell adenocarcinoma, congenital Müllerian anomalies
Teratogens medications
- Isotretinoin
- Lithium
- Methimazole
- Tetracyclines
Multiple severe birth defects (Contraception mandatory)
Ebstein anomaly
Aplasia cutis congenita
Discolored teeth, inhibited bone growth
Teratogens medications
- Thalidomide
- Warfarin
Liimb defects
Bone deformities, fetal hemorrhage, abortion, ophthalmologic abnormalities
Teratogens Substance abuse
- Alcohol
- Cocaine
- Smoking (nicotine, CO)
birth defects and intellectual disability; fetal alcohol syndrome
Low birth weight, preterm birth, IUGR, placental abruption
Low birth weight, preterm labor, placental problems,
IUGR, SIDS, ADHD
Teratogens Others
- Iodine (lack or excess)
- Methylmercury
- Vitamin A excess
- X- rays
Congenital goiter or hypothyroidism (cretinism)
Neurotoxicity
Extremely high risk for spontaneous abortions and birth defects
Microcephaly, intellectual disability
Teratogens Others
- Maternal diabetes
Caudal regression syndrome (anal atresia to sirenomelia), congenital heart defects, neural tube defects, macrosomia, neonatal hypoglycemia, polycythemia
Fetal alcohol syndrome
- Epidemiology
- CLinical manifestations
- Mechanism
Leading cause of intellectual disability in the US.
microcephaly, facial abnormalities, limb dislocation, heart defects. Heart-lung fistulas and holoprosencephaly in most severe form
Mechanism is failure of cell migration.
Neonatal abstinence syndrome
Secondary to maternal opiate use/abuse.
Newborns may present with uncoordinated sucking reflexes, irritability, high-pitched crying, tremors, tachypnea, sneezing, diarrhea, and possibly seizures.
Twinning Monozygotic
- timing of cleavage
(SCAB):
Cleavage 0–4 days: Separate chorion and amnion
Cleavage 4–8 days: shared Chorion
Cleavage 8–12 days: shared Amnion
Cleavage 13+ days: shared Body (conjoined)
Placenta Fetal component
- Cytotrophoblast
- Syncytiotrophoblast
Inner layer of chorionic villi. Cytotrophoblast makes Cells.
Outer layer of chorionic villi; synthesizes and secretes hormones (Lacks MHC-I expression).
Placenta Maternal component
- Desidua basalis
Derived from endometrium. Maternal blood in lacunae.
Pag. 599
Umbilical cord
- Umbilical arteries (2)
- Umbilical vein (1)
- Both derived from allantois.
return deoxygenated blood from fetal internal iliac arteries to placenta
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
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
Obliterated urachus is represented by the median umbilical ligament after birth
Urachus
- Patent urachus
- Vesicourachal diverticulum
Total failure of urachus to obliterate urine discharge from umbilicus
Slight failure of urachus to obliterate outpouching of bladder.
Urachus
- Urachal cyst
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
Vitelline duct
7th week—obliteration of vitelline duct (omphalomesenteric duct), which connects yolk sac to
midgut lumen.
Vitelline duct
- Vitelline fistula
- Meckel diverticulum
Vitelline duct fails to close meconium discharge from umbilicus.
Partial closure of vitelline duct, with patent portion attached to ileum (true diverticulum). Melena, hematochezia, abdominal pain.
Aortic arch derivatives
- 1st
- 2nd
- 3rd
Part of maxillary artery
Stapedial artery and hyoid artery
Common Carotid artery and proximal part of internal Carotid artery.
Aortic arch derivatives
- 4th
- 6th
On left, aortic arch; on right, proximal part of right subclavian artery
Proximal part of pulmonary arteries and (on left only) ductus arteriosus
Branchial apparatus
CAP covers outside to inside:
Clefts = ectoderm
Arches = mesoderm + neural crest
Pouches = endoderm
Branchial arch derivatives
Branchial pouch derivatives
Pag. 602
Pag. 603
Pierre Robin sequence
micrognathia, glossoptosis, cleft palate, airway obstruction
Treacher Collins syndrome
neural crest dysfunction mandibular hypoplasia, facial abnormalities
DiGeorge syndrome
Chromosome 22q11 deletion. Aberrant development of 3rd and 4th pouches thymic aplasia and failure of parathyroid development. Associated with cardiac
defects (conotruncal anomalies)
Cleft lip
Cleft palate
Failure of fusion of the maxillary and merged medial nasal processes (formation of 1° 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).
Genital embryology
- Male
SRY gene on Y chromosome—produces testisdetermining factor testes development.
Sertoli cells secrete MIF that suppresses development of paramesonephric ducts.
Leydig cells secrete androgens that stimulate development of mesonephric ducts.
Genital embryology
- Female
Mesonephric duct degenerates and paramesonephric duct develops
Müllerian agenesis (Mayer-Rokitansky- Küster-Hauser syndrom)
1° amenorrhea (due to a lack of uterine development) in females with fully developed 2° sexual characteristics (functional ovaries).
Mesonephric (Wolffian) duct
Develops into male internal structures (except prostate) Seminal vesicles, Epididymis, Ejaculatory duct, Ductus deferens (SEED).
*Female remnant is Gartner duct
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.
No Sertoli cells or lack of Müllerian inhibitory factor
develop both male and female internal genitalia and male external genitalia
5α-reductase deficiency
inability to convert testosterone into DHT male internal genitalia, ambiguous external genitalia until
puberty (when testosterone levels cause masculinization)
Uterine (Müllerian duct) anomalies
- Septate uterus
- Uterus didelphys
Incomplete resorption of septum. low fertility and early
miscarriage/pregnancy loss. Treat with septoplasty
Complete failure of fusion double uterus, cervix, vagina. Pregnancy possible.
Uterine (Müllerian duct) anomalies
- Bicornuate uterus
Incomplete fusion of Müllerian ducts. risk of complicated pregnancy, early pregnancy loss, malpresentation, prematurity
Male/female genital homologs
Pag. 605
Congenital penile abnormalities
Hypospadias: Associated with inguinal hernia and
cryptorchidism
Epispadias: Exstrophy of the bladder is associated with
Epispadias.
Descent of testes and ovaries
- Gubernaculum
- Processus vaginalis
Band of fibrous tissue. Anchors testes within scrotum. Ovarian ligament + round ligament of uterus.
Evagination of peritoneum. Forms tunica vaginalis (male). Obliterated (female)
