External Appearance – 2 Month
External appearance – 2nd month (week 5 – week 8)
55th ––88th weekweek periodperiod isis thethe timetime ofof organogenesisorganogenesis AtAt thethe endend ofof thethe 44th weekweek thethe mainmain externalexternal featuresfeatures areare thethe somitessomites andand pharyngealpharyngeal archesarches InIn 22 nd monthmonth thethe ageage ofof thethe embryoembryo isis indicatedindicated asas crowncrown --rumprump lengthlength (CRL)(CRL) asas countingcounting somitessomites becomesbecomes difficultdifficult CRLCRL isis thethe distancedistance fromfrom thethe vertexvertex ofof thethe skullskull toto thethe midpointmidpoint betweenbetween thethe apicesapices ofof thethe buttocksbuttocks inin millimetersmillimeters AtAt thethe endend ofof thethe embryonicembryonic period,period, thethe embryoembryo hashas humanhuman appearanceappearance Crown-Rump Length correlated to age External appearance the embryo LateralLateral viewview ofof aa 55 --weekweek --oldold embryoembryo The embryonic period is divided into 2323 CarnegieCarnegie stagesstages based on external and internal morphological criteria
CRL WeekWeek 55 -- summarysummary WeeksWeeks 66 --88 -- summarysummary External appearance the fetus
weeks SizeSize ofof thethe fetusfetus
At the junction of trimesters 1 and 2 (=90 days old) → length of 90 mm At the junction of trimesters 2 and 3 (2→3), the fetus is ~ 250 mm in length and weighs ~ 1,000g 12 weeks 7 months Development of the head & neck
Early stages - transformation of the head (cephalic) folds neural walls with the eye primordia otic disc & pharyngeal arches lens & nasal placodes Development of the human face is usually described as a process of merging of 5 swellings (growth centres) surrounding the stomodeum, termed processes (prominences) bilateral maxillary processes bilateral mandibular processes frontonasal prominence PharyngealPharyngeal archesarches CS 15, day 36 Series of bulges on the lateral surface of the es) (groov head and neck clefts Separated by clefts (grooves) 4 pairs are visible by day 30 arches More caudally, no clear-cut arrangement, but a 5th and a 6th arch are distinguished Clefts have internal counterparts, the pharyngeal pouches EarlyEarly 44 thth weekweek
Cranial and The developing cervical face is regions make represented by up ~ 50% of the frontonasal up ~ 50% of region, and the the embryo's first pharyngeal length (branchial, visceral) arch LateLate 44 thth –– earlyearly 55 thth weekweek
By the time the anterior neuropore closes, the first and second pharyngeal arches are evident The regions between the pharyngeal arches are termed pharyngeal clefts. The indentation just dorsal to the second pharyngeal cleft is the Otic pit developing inner ear, the otic pit.
Otic pit EarlyEarly 55 thth weekweek
Frontonasal TheThe 11 st pharyngealpharyngeal archarch prominence hashas bothboth aa maxillarymaxillary andand aa mandibularmandibular prominence.prominence. trigeminal maxillary DorsalDorsal toto thethe firstfirst archarch isis anan elevationelevation formedformed byby thethe underlyingunderlying trigeminaltrigeminal ganglionganglion thatthat suppliessupplies tissuestissues derivedderived fromfrom thethe mandibular firstfirst archarch EarlyEarly 55 thth weekweek
EpibranchialEpibranchial placodesplacodes areare specializedspecialized regionsregions ofof surfacesurface ectoderm,ectoderm, thethe cellscells ofof whichwhich invaginateinvaginate toto contributecontribute toto thethe formationformation ofof thethe sensorysensory gangliaganglia ofof cranialcranial nervesnerves V,V, VII,VII, IX,IX, andand XX DayDay 2929
buccopharyngeal stomodeum membrane neural neural tube tube
1st arch 1st arch
pharynx pouches clefts
Remnants of the Clefts separate the buccopharyngeal pharyngeal arches on membrane are seen the external surface between the Pouches separate the stomodeum and the pharyngeal arches on pharynx the internal surface CompositionComposition ofof anan archarch
ectoderm endoderm
The mesenchyme of the arches is derived in part from neural crest and in part from mesoderm DerivativesDerivatives ofof thethe pharyngealpharyngeal pouchespouches SomeSome ofof thethe neuralneural crestcrest cellscells inin eacheach ofof thethe archesarches becomebecome cartilagecartilage TheThe pharyngealpharyngeal archesarches contributecontribute toto thethe developingdeveloping tonguetongue andand epiglottisepiglottis PharyngealPharyngeal archesarches -- dayday 3535
TheThe 11 st ,, 22 nd ,, 33 rd ,, andand 44 th archesarches areare visiblevisible 1 externally.externally. TheThe sixthsixth 1 archarch doesdoes notnot formform anan 2 externalexternal elevation.elevation.
3 4 TheThe frontonasalfrontonasal prominenceprominence isis composedcomposed ofof thethe tissuetissue thatthat surroundssurrounds thethe forebrainforebrain –– dayday 3535 FollowingFollowing closureclosure ofof thethe anterioranterior neuropore,neuropore, thethe ectectodermoderm thatthat willwill lineline thethe nasalnasal cavitiescavities (( olfactoryolfactory placodesplacodes )) isis locatedlocated onon thethe laterallateral aspectsaspects ofof thethe frontonasalfrontonasal prominenceprominence –– dayday 3535
olfactory placode olfactory placode DuringDuring 55 th weekweek thethe olfactoryolfactory placodesplacodes lineline thethe nasalnasal pitspits
olfactory placode
medial nasal prominences
lateral nasal prominence nasal pit CompositionComposition ofof thethe olfactoryolfactory placodeplacode
lateral nasal prominence mesenchyme
olfactory placode epithelium
medial nasal prominence mesenchyme UpperUpper liplip formationformation –– 66thth weekweek
medial
Contribution of each of the prominences to the face Union of the medial nasal prominence with the lateral nasal prominence and maxillary prominence is required for normal development of the upper lip At 8 th week the face has human features CraniofacialCraniofacial defectsdefects
Complete holoprosencephaly was diagnosed by ultrasound at 22 weeks of gestation, after which pregnancy was terminated at 24 weeks. At autopsy, the female fetus showed agenesis of both eyes and orbits,arhinia and microstomia. LimbLimb developmentdevelopment
ByBy thethe beginningbeginning ofof thethe 55th week,week, forelimbsforelimbs andand hindlimbshindlimbs appearappear asas paddlepaddle --shapedshaped budsbuds BBudsuds flattenflatten →→ radialradial groovesgrooves (rays)(rays) appearappear onon thethe distaldistal portionportion ofof thethe budsbuds →→ digitsdigits LimbLimb DevelopmentDevelopment (late(late weekweek 4,4, dayday 28)28)
lower
TheThe developingdeveloping upperupper limblimb isis evidentevident earlierearlier thanthan thethe lowerlower limblimb
upper LimbLimb developmentdevelopment (late(late weekweek 4,4, dayday 28)28)
A cut through the limb bud illustrates the mesenchyme which is derived from the lateral plate mesoderm (the source of the skeletal components) and from the myotomes of the paraxial mesoderm (the muscular component) LimbLimb developmentdevelopment (week(week 5,5, dayday 33)33)
The thickened ectoderm at the distral rim of the limb bud is termed the apical ectodermal ridge . Integrity of the apical ectodermal ridge is essential for continued limb outgrowth. LimbLimb developmentdevelopment (week(week 5,5, dayday 36)36)
As the limb bud grows, indentations become apparent in the hand (or foot) plate LimbLimb developmentdevelopment (Week(Week 7)7)
During the 7 th & 8 th weeks of human development the digits of the hand become apparent LimbLimb developmentdevelopment (Week(Week 8)8)
At the beginning of the fetal period, touch pads are prominent features of the hands and feet LimbLimb developmentdevelopment (week(week 8)8)
As the hand develops, webs that are present between the outgrowing digits must regress Development of the feet is like that of the hands, but in the human it starts approximately 3 -4 days later FormationFormation ofof thethe cardiogeniccardiogenic fieldfield
Cardiac progenitor cells lie in the epiblast, A immediately lateral to the primitive streak Y Migrate through the streak → position in front of the neuroectoderm at day 18 the intraembryonic cavity over the cardiogenic field later develops into the pericardial cavity HeartHeart tubetube formationformation –– ~day~day 2020
1 Pericardial cavity 2 Myoepicardium 3 Endocardium 4 Midgut
This is a frontal section through the cardiac anlage. The endothelial cells differentiate out of the neighboring mesenchymal cells of the splanchnopleurae and flow together to make up numerous vesicles that form the endocardial plexus . The myocardial mantle arises out of the material of the cardiogenic plate. RapidRapid growthgrowth ofof thethe developingdeveloping brainbrain pushespushes thethe heartheart tubetube ventrallyventrally
Rapid growth of the developing brain produces more caudal and ventral positioning of the cardiogenic region and formation of the foregut As the neural cells proliferate and grow forward, the cardiogenic area is folded over and the endoderm -lined foregut is formed EarlyEarly 44 thth week,week, dayday 2222
Neural folds The septum transversum is located just below the developing heart , which at this stage, begins to beat
Neural folds BodyBody cavitiescavities (early(early weekweek 4,4, dayday 23)23)
The body cavity, which forms between the splanchnic and somatic mesoderm, becomes divided by the septum transversum into the pleuropericardial cavity and the peritoneal cavity
ventral view BodyBody cavitiescavities (mid(mid --weekweek 4,4, dayday 26)26)
The septum transverum is the primordium of the diaphragm which is located just rostral to the developing liver. Bilateral passageways (pericardioperitoneal canals) connect the pleuropericardial and peritoneal portions of the body cavity at this developmental stage BodyBody cavitiescavities (week(week 7)7)
heart lung
diaphragm gut liver
Separation of the space containing the lungs and heart (pleuropericardial cavity) and that with the liver and gut (peri toneal cavity) is completed as the diaphragm forms with contributions f rom the septum transverum, the pleuroperitoneal folds and the body wall MidMid --44thth week,week, dayday 2424
BloodBlood entersenters thethe caudalcaudal aspectaspect ofof thethe heartheart tubetube andand leavesleaves inin thethe regionregion ofof thethe formingforming visceralvisceral archarch EmbryonicEmbryonic bloodblood circulationcirculation
Pericardium Cranial ectoderm Heart tube
Yolk sac Dorsal aorta
Amnion
Umbilical vein
Umbilical artery
Allantois Chorionic plate Placental villi Vitelline circulation BloodBlood flowflow –– dayday 2525 vitelline vein ↓ sinus venosus ↓ primitive atria ↓ primitive ventricles ↓ bulbous cordis ↓ visceral arch vessels ↓ dorsal aorta ↓ vitelline vein BloodBlood flowflow intointo thethe sinussinus venosusvenosus isis fromfrom 33 pairspairs ofof vesselsvessels (day(day 25)25)
Cardinal veins (drain the embryo) Vitelline veins (from yolk sac) Umbilical vein (from placenta) Oxygenated blood mixes with deoxygenated blood
in the liver (I) in the inferior vena cava (II) in the right atrium (III ) in the left atrium (IV) at the entrance of the ductus arteriosus into the descending aorta (V) Some blood bypasses the liver via the At birth the ductus arteriosus closes so ductus venosus. Passage through the that blood in the pulmonary trunk is no lungs is diminished because blood in the longer shunted into the aorta pulmonary trunk is shunted into the aorta FetalFetal vsvs postnatalpostnatal circulationcirculation
Umbilical vein v.cava inf.
Umbilical arteries
TimetableTimetable ofof developmentdevelopment ofof thethe bodybody systemssystems EmbryonicEmbryonic membranesmembranes
AmnionAmnion ChorionChorion YolkYolk (vitelline)(vitelline) sacsac AllantoisAllantois EpiblastEpiblast && hypoblasthypoblast formform 22 embryonicembryonic membranesmembranes
AmnionAmnion –– formedformed byby epiblast;epiblast; filledfilled withwith amnioticamniotic fluidfluid providesprovides aa protectiveprotective environmentenvironment forfor thethe embryoembryo helpshelps maintainmaintain aa constantconstant homeostatichomeostatic temperaturetemperature amnioticamniotic fluidfluid comescomes fromfrom maternalmaternal blood,blood, andand laterlater,, fetalfetal urineurine YolkYolk sacsac –– hypoblasthypoblast cellscells thatthat formform aa sacsac onon thethe ventralventral surfacesurface ofof thethe embryoembryo FormsForms partpart ofof thethe digestivedigestive tubetube ProducesProduces earliestearliest bloodblood cellscells andand vesselsvessels FormationFormation ofof amnioticamniotic cavitycavity
Within the sphere of epiblast cells , some cells (next to the hypoblast) become more columnar epiblast Epiblast sphere become s flattened hypoblast Fluid accumulates → amniotic cavity forms FormationFormation ofof primaryprimary yolkyolk sacsac
day 9 Hypoblast cells migrate and cover the cytotrophoblast 2 hypoblast layers are formed: parietal – in contact with the cytotrophoblast; =exocoelomic (Heuser ’s) membrane visceral – in contact with epiblast visceral hypoblast parietal hypoblast primary yolk sac PinchingPinching offoff thethe primaryprimary yolkyolk sacsac producesproduces secondarysecondary yolkyolk sacsac
~ Day 13 the hypoblast produces additional cells that gradually form a new cavity within the primary yolk sac → secondary (definitive) yolk sac Secondary yolk sac is much smaller than primary yolk sac The pinched portions of primary yolk sac → exocoelomic cysts GraduallyGradually amnionamnion expandsexpands whilewhile yolkyolk sacsac disappearsdisappears
amnion
yolk sac
amnion
yolk sac Amniotic fluid
Clear, watery fluid, derived primarily from maternal blood Volume: 30 ml (8 weeks) → 450 ml (20 wk) → 800- 1000 ml (at birth) Functions absorbs stress on the embryo/fetus prevents adherence of the embryo to the amnion allows for fetal movements Polyhydramnios/oligohydramnios → increased/decreased volume → birth defects Chorion frondosum
Chorion laeve Yolk sac stalk Yolk sac DerivationDerivation ofof chorionchorion
embryo, amnion, yolk sac PrimaryPrimary villivilli –– dayday 1313
day 9
day 13 Cells of the cytotrophoblast proliferate locally and penetrate into the syncytiotrophoblast, forming cellular columns surrounded by syncytium These columns are primary villi Development of trophoblast in 3 rd week
day 13
Mesodermal cells penetrate the core of primary villi and grow toward the decidua → secondary villi
day 13 day 15 Development of trophoblast in 3 rd week
By the end of 3 rd week, mesodermal cells in the core of the villus begin to differentiate into blood cells and vessels, forming the villous capillary system → tertiary (definitive, placental) villi Development of trophoblast – end of 3 rd week
Cytotrophoblastic cells surround the trophoblast entirely (form outer shell) and are in direct contact with the endometrium The outer shell gradually surrounds the trophoblast entirely and attaches the chorionic sac firmly to the maternal endometrial tissue Embryo is suspended in the chorionic cavity by means of the connecting stalk StemStem vsvs terminalterminal tertiarytertiary villivilli
stem villus
terminal villus
Stem (anchoring ) villi - extend from the chorionic plate to the endometrium Terminal (f ree) villi - branch from the sides of stem villi → through them exchange of nutrients will occur Development of trophoblast – end of 3 rd week
Maternal vessels ↓ Intervillous space ↓ Trophoblast ↓ Villous capillary ↓ Chorionic plate vessels (=extraembryonic ↓ somatopleuric mesoderm) Intraembryonic vessels
Maternal vessels penetrate the cytotrophoblastic shell to enter intervillous spaces, which surround the villi. Capillaries in the villi are in contact with vessels in the chor ionic plate and in the connecting stalk, which in turn are connected to intraembryonic vessels PlacentaPlacenta isis fullyfully formedformed andand functionalfunctional byby thethe endend ofof thethe 33 rd monthmonth
4th week 4th month
wall of the capillaries is in direct contact with the syncytium Chorion compartments
Villi on the embryonic pole continue to grow and expand, giving rise to the chorion frondosum (bushy) Villi on the abembryonic pole degenerate and by the 3rd month → chorion laeve (smooth) DuringDuring pregnancypregnancy endometriumendometrium isis calledcalled deciduadecidua Placenta is composed of cells derived from two genetically distinct individuals
Placenta = fetal part ( chorion ) + maternal part ( decidua basalis ) Relation of fetal membranes to wall of the uterus The amnion and chorion have fused (amniochorionic membrane ), and the uterine cavity is obliterated
8th week 12 th week Cotyledon cotyledon
In the second half of pregnancy, decidual (maternal) septa form, which project into intervillous spaces but do not reach the chorionic plate Thus, the placenta is divided into a number of compartments → cotyledons At full term, the placenta is discoid
Measures Umbilical cord diameter 15 - 25 cm ~3 cm thick weighs ~ 500 to 600 g
Umbilical cord
Amnion Totally: 15-25 PlacentaPlacenta -- histologyhistology
DB = decidua basalis AV = anchoring (stem) villi IS = intervillous spaces TV = terminal (free) villi PlacentaPlacenta –– histologyhistology (high(high mag.)mag.)
Ме = mesenchyme ВV = blood vessels IS = intervillous spaces TV = terminal (free) villi ST = syncytiotrophoblast FunctionsFunctions ofof placentaplacenta
Exchange of Gases Exchange of Nutrients and Electrolytes Transmission of Maternal Antibodies Hormone Production AAllantoisllantois When the cloacal membrane appears (day 16), the posterior wall of the yolk sac allantois stalk forms a small diverticulum that extends into the epiblast connecting stalk → allantois A little out -pocketing of the hypoblast caudal end of yolk sac trapped in the connecting caudal trapped in the connecting cranial stalk This blind pouch is called the allantois (Gr., sausage -shaped ) Importance structural base for the umbilical cord becomes part of the urinary bladder CConnectingonnecting stalkstalk →→ umbillicalumbillical cordcord
Continued development and expansion of the extraembryonic coelom restricts the attachment of the embryonic disk to a connecting stalk, which is a permanent connection between the future caudal end of the embryonic disc and the chorion The connecting stalk forms a pathway along which vascular Connecting stalk anastomoses of embryonic disk establish communication with those of the chorion → future umbilical cord StructuresStructures passingpassing viavia thethe umbilicalumbilical ringring –– 55th weekweek
Connecting stalk allantois umbilical vessels (2 arteries + 1 vein) Yolk stalk (vitelline duct ), accompanied by the vitelline vessels Canal connecting the intraembryonic and extraembryonic cavities AfterAfter embryoembryo foldingfolding && amnionamnion enlargementenlargement
10 th week – primitive umbilical cord amnion
yolk sac
Distally yolk sac stalk umbilical vessels (2 arteries + 1 vein) Proximally – intestinal loop (physiological umbilicall hernia) as the GI tract growth is too fast → withdrawn after 3 rd month Finally remain the umbilical vessels and loose connective tissue (jelly of Wharton) Umbilical vein vs artery
Umbilical vein Umbilical artery Jelly of Wharton TwinsTwins
DizygoticDizygotic ((fraternalfraternal )) 70% of twins; 7-11 per 1000 births ovulation of 2 oocytes and fertilization by 2 different spermatozoa → may or may not be of different sex; no more resemblance than any other brothers or sisters MonoMono zygoticzygotic (identical)(identical) 30% of twins; 3 -4 per 1000 births 1 oocyte & 1 spermatozoon → splitting of the zygote at various stages of development (2 -cell stage or blastocyst stage or bilaminar disk stage) TripletsTriplets areare rarerare (about(about 1/76001/7600 pregnancies),pregnancies), birthbirth ofof quadruplets,quadruplets, quintuplets,quintuplets, andand soso forthforth isis rarerrarer DizygoticDizygotic twinstwins splitting at splitting at 2-cell stage bilaminar disk stage MonoMono zygoticzygotic twinstwins splitting at blastocyst stage Partial splitting of the primitive node and streak → conjoined (Siamese) twins TeratologyTeratology
Birth defect, congenital malformation, and congenital anomaly are synonymous terms used to describe structural, behavioral, functional, and metabolic disorders present at birth Teratogens (Gr. teratos, monster + gen, producing) Major structural anomalies occur in 2 to 3% of liveborn infants, and an additional 2 to 3% are recognized in children by age 5 years – totally 4-6% Terms and concepts relating to malformations CausesCauses ofof ccongenitalongenital mmalformationsalformations Critical periods in human development and site of action of teratogens The most sensitive period for inducing birth defects is the third to eighth weeks of development, the period of embryogenesis Thalidomide
Taken as a sedative in early pregnancy, thalidomide proved to be a teratogen with severe effects on embryonic limb development DownDown ’’ss syndromesyndrome –– thethe most common autosomal anomaly
epicanthal fold over the medial commissure of the eye Invasive sampling tests
Chorion villus sampling Amniocentesis Fetal blood sampling st 1 trimester → The most common From umbilical cord possibility of an early technique Age: 4 -4,5 months termination of Age: 2 -2,5 months For chromosomal pregnancy For chromosomal Indications – similar analysis after other to chorion villus methods have shown sampling anomaly