General Embryology PDF

General embryology  Male & female gametes *Formation: Male gametes (sperms) & female gametes (ova) are reproductive cells, formed from primordial germ cells. Process is called spermatogenesis in male and oogenesis in female....

General embryology  Male & female gametes *Formation: Male gametes (sperms) & female gametes (ova) are reproductive cells, formed from primordial germ cells. Process is called spermatogenesis in male and oogenesis in female. *Site: In gonads (testis or ovary). *Time: a)In males, it starts at puberty & continues till old age. b)In females, it starts in intrauterine life then arrested to be continued from puberty to menopause through ovarian cycles. Ovulation occurs at 14th day of ovarian cycle. *Morphology: Sperm Ovum A human sperm is 55 microns long & consists of: Diameter of mature ovum is about 120 1-Head; 4 microns long, contains: *Condensed nucleus microns & consists of: which carries hereditary material of father (22 autosomes 1-Ootid (mature oocyte) which carries; & X or Y sex chromosomes), mostly covered by acrosomal *Nucleus which has hereditary material of cap which has enzymes facilitating ova covering penetration mother (22 autosomes & X sex chromosome). (fertilization). *Minimal cytoplasm *Cell membrane. *Large cytoplasm which is initial source of 2-Neck; narrow part between head & middle piece. zygote nutrition. *Cell membrane. 3-Middle piece; 6 microns long, formed of mitochondrial 2-Zona pellucida; glycoprotein coat around sheath which is energy source for sperm motility. ootid. Carries sperm receptors for sperm 4-Tail; 45 microns long, formed of axial filament with cell attraction prior to fertilization. membrane around most of it. It directs sperm movement 3-Corona radiata; outer cover formed of towards ovum then helps fertilization. follicular cells derived from ovary. First week of development 1-Fertilization *Def.: Union between male gamate (sperm) & female gamate (ovum) to form zygote. *Site: Ampulla of uterine tube. *Mechanism: 1-Sperms capacitation: Process of glycoprotein coat removal from acrosomal regions of sperms in female genital system, taking about 7 hours to be completed. 2-Phase I (corona radiata penetration): Only 300 – 500 sperms out from 200 – 300 million sperm / ejaculation will reach ovum & start corona radiata dispersion. 3-Phase II (zona pellucida penetration): One sperm only will pass through the zona pellucida by following steps; a)Sperms bind to zona at specific binding sites (sperm receptors). b)Sperms secrete acrosomal enzymes (acrosin & trypsin like substances) which dissolve passage through zona, only one sperm will pass through zona pellucida (acrosomal reaction) by tail movement. c)Fertilizing sperm head comes in contact with 2nd oocyte plasma membrane. 4-Phase III (Penetration of oocyte cell membrane): It occurs by following steps; a)Plasma membranes of sperm & ovum fuse together. b)Fused plasma membranes open to allow passage of sperm contents (nucleus, neck, middle piece & axial filament) to ovum cytoplasm, leaving sperm cell membrane on oocyte outer surface. 5-Events occurring after sperm entrance to oocyte cytoplasm: a)Cortical & zona reactions; after fertilizing sperm entrance, oocyte releases lysosomal enzymes from cortical granules which prevent polyspermy through: 1-Changing sperm binding sites of zona pellucida to prevent binding & passage of more sperms. 2-Making fertilized oocyte plasma membrane impenetrable to other sperms. b)2nd oocyte completes 2nd meiotic division to form mature ovum (ootid) (23 Ch.) & 2nd polar body (23 Ch.). c)Male nucleus becomes larger (male pronucleus) & come in contact with ootid nucleus (female pronucleus). d)Nuclear membranes of male & female pronuclei fuse forming zygote nucleus. *Results: 1-Zygote formation. 2-Sex determination; either male (XY) or female (XX). 3- Diploid number (46 Ch.) restoration. 4Start of cleavage & zygote migration from fertilization site to implantation site in uterine cavity.  Artificial fertilization In vitro fertilization (IVF) Intracytoplasmic sperm Gamete intra-fallopian injection (ICSI) transfer (GIFT) *Performed in female suffering from obstructed *Performed in case of low uterine tubes. sperms count or failure of Oocytes & sperms *Giving mother gonadotropins to stimulate FSH its penetration to oocyte walls. are introduced into secretion which induce multiple Graafian follicles fallopian (uterine) formation in ovary. 2ND oocytes withdrawal from *In-vitro injection of single tube ampulla, where Graafian follicles just before ovulation using sperm into oocyte cytoplasm fertilization takes laparoscope & their transfer to a special culture to cause fertilization. After place. Development medium, then sperms addition. morula formation, it is then proceeds in a implanted into uterine normal manner. *When fertilization occurs & embryo reaches 8- endometrium using catheter. cell stage, it is taken from culture medium & implanted in endometrium. 2-Cleavage & migration -Zygote divides mitotically inside zona pellucida, giving rise to smaller blastomeres (46 Ch.) in following manner: *Two cell stage in 1st day *Four cell stage in 2nd day. *16 cell stage (morula) followed by 32 & 64 cell stage in 3rd day. -During cleavage, morula migrates inside uterine tube to reach uterine cavity at 4th day by uterine tube muscular peristalsis & cilia motion of tube mucosal lining. 3- Blastocyst formation *Zona pellucida starts to degenerate at end of 5th day. *Fluid pass through degenerating zona to form multiple spaces between morula cells. Gradually those spaces fuse together forming single cavity (blastocele), this stage is named blastocyst which is composed of: 1-Outer cell mass (trophoblast); single layer of cells. 2-Inner cell mass (embryoblast); mass of cells on one side of trophoblast inner aspect. 3-Blastocele; blastocyst cavity. 4-Embryonic pole; blastocyst side corresponding to embryoblast. 5-Abembryonic pole; opposite side of blastocyst embryonic pole.  Second week of development 1-Implantation *Def.: Process by which blastocyst becomes embedded in endometrium. *Time: Starts at 7th day & completed at 11th day. *Site: In endometrium of upper part of post. wall uterus (near fundus), less frequent in upper part of ant. wall. N.B.: During implantation, endometrium is at secretory phase of endometrial (menstrual) cycle. It is characterized by increased endometrial thickness, increased number & size of endometrial cells, glands are spiral & rich with secretions, arteries are spiral & showing arterio-venous anastomosis. *Mechanism: a)Starts by blastocyst adhesion by its embryonic pole to implantation site of endometrium. b)Trophoblast proliferate at embryonic pole forming new cell layer with no cell walls (syncytiotrophoblast) which secretes proteolytic enzymes that erode endometrium & form implantation cavity. c)Blastocyst becomes embedded inside the cavity. d)At 9th day, penetration site becomes blocked by fibrin clot. e)2 days later (11th day), endometrial epithelium overgrows &covers fibrin clot. *Changes of blastocyst during implantation: 1-Trophoblast differentiates into outer syncytiotrophoblast and inner cytotrophoblast, starting at embryonic pole then extends all over blastocyst. 2-Formation of amniotic & yolk sac cavities. 3-Formation of double layered embryonic disc (epiblast & hypoblast). *Abnormal sites of implantation: a)Placenta previa: Implantation occurs at uterus lower segment. 3 types; 1-Placenta previa parietalis: Placenta margin is near internal os. 2-Placenta previa marginalis: Placenta margin covers internal os. 3-Placenta previa centralis: Placenta center covers internal os. N.B. -Internal os is inner opening of cervical canal of uterus. -Placenta previa is life threatening as it leads to antepartum (before birth) maternal hemorrhage & may lead to fetus death. So, cesarean section is highly recommended in placenta previa.  b)Ectopic pregnancy: Blastocyst is abnormally implanted outside uterus in following sites: -Tubal; in uterine tube which may occur in ampulla, isthmus or intramural parts. Tubal rupture is expected at 8th week of pregnancy leading to severe internal hemorrhage. -Ovarian; on ovary surface -Omental; in abdominal or pelvic peritoneum. Decidua * Def.: Endometrium of uterus after blastocyst implantation. It is called decidua as it sheds during labor (Latin word, meaning falling off or shedding). It is exaggerated endometrial secretory phase. *Features: Increased endometrial thickness, increased number & size of endometrial cells, glands become spiral & full of secretions, arteries are spiral & show arterio-venous anastomosis. *Parts: 1-Decidua basalis: Part between implanted embryo & myometrium. 2-Decidua capsularis: Part covering embryo, separating it from uterine cavity. 3-Decidua parietalis: Part lining rest of uterine cavity. *Fate: -Decidua basalis: Persists as placenta maternal part. -Decidua capsularis & parietalis: Come in contact & fuse obliterating uterine cavity to degenerate at last. 2-Daily events during 2nd gestational week 8th day 9th & 10th days 1)Blastocyst is partially implanted. 1)Blastocyst is completely implanted. 2)Trophoblast layer differentiates into inner cytotrophoblast & outer syncytio-trophoblast, 2)Penetration site is closed by fibrin clot. starting at blastocyst embryonic pole. 3)Cells of inner cell mass (facing blastocele) 3)Syncytiotrophoblast extends to surround become cuboidal forming hypoblast layer. cytotrophoblast of whole blastocyst. 4)Amniotic cavity appears within embryoblast. Cells adjacent to cytotrophoblast secrete amniotic 4)Lacunae appear in syncytiotrophoblast (Lacunar stage). fluid & known as amnioblast cells. Amniotic cavity separates amnioblast & epiblast of embryonic disc. 5)Flat cells (Heuser’s membrane) from hypoblast, 5)Epiblast & hypoblast form bilaminar embryonic disc. line blastocele transforming it into 1ry yolk sac.  11th & 12th days 13th day 1)Endometrial epithelium grows 1)Fusion of extraembryonic mesoderm spaces leads to formation of & covers fibrin colt. extra-embryonic coelom (chorionic cavity). Now blastocyst is called chorionic vesicle & its wall is called chorion. Chorionic cavity separates between somatic & splanchnic mesoderm. Somatic 2)Lacunae fill with maternal blood forming utero-placental circulation. mesoderm lines cytotrophoblast & covers amniotic cavity, while splanchnic mesoderm covers yolk sac. 2)Connecting stalk is extraembryonic mesoderm part which 3)Extra-embryonic mesoderm is connects embryonic disc caudal end with chorion. formed between cytotrophoblast nd 3)New cells generation from hypoblast, line 1ry yolk sac to form 2 yolk sac. (externally) & embryonic disc with amniotic & yolk sac cavities 4)Pinching off 2nd yolk sac large part with marked reduction of its size. (internally). Multiple spaces appear 5)Allantois formation which extends from yolk sac caudal wall. in extraembryonic mesoderm. 6)1ry chorionic villi start to appear from chorion. THIRD week of development 1-Chorion development -Chorion is chorionic vesicle wall, formed of somatic extraembryonic mesoderm, cytotrophoblast & syncytiotrophoblast (from internal to external). It secretes chorionic gonadotropin which maintains corpus luteum (progesterone source in ovary) for 4 months. -Chorionic villi *Def.: Projections from chorion (chorionic vesicle wall). *Time of formation: Start at 2nd gestational week end then continues during 3rd week. *Types: a)Primary villi: Cytotrophoblast cells proliferate & push syncytio- trophoblast forming primary villi, which are separated from each other by lacunae filled with maternal blood. b)Secondary villi: Formed when somatic extraembryonic mesoderm enters primary villi core, at middle of 3rd week. c)Tertiary villi: Formed when fetal blood vessels appear in secondary villi mesoderm at 3rd week end. Separated by intervillous spaces filled with maternal blood. Cytotrophoblastic shell is formed when cytotrophoblast cells penetrate syncytiotrophoblast at stem villi apices & extend to surrounds chorionic villi & intervillous spaces. *Parts of tertiary villous: Each villous is composed of; 1-Stem (anchoring) villous: Villous extending between chorion & decidua basalis. 2-Free (floating or absorbing) villi: Side branches from stem villous, floating in maternal blood inside intervillous spaces. Responsible for nutrient & gases exchange with maternal blood. -Parts of chorion: a)Chorion frondosum (chorionic plate): Part carrying well developed tertiary villi & facing decidua basalis. b)Chorion laeve: Rest of chorion carrying degenerating tertiary villi & covered with decidua capsularis. -Fate of chorion: Chorion frondosum (chorionic plate) persists sharing in placenta formation, while chorion laeve degenerates. 2-Gastrulation *Def.: Transformation of bilaminar embryonic disc into trilaminar disc, starting by development of primitive streak & primitive node in epiblast layer. *Primitive streak: Formed in midline of embryonic disc caudal part as a median narrow groove with bulging sides. Developed from proliferation & migration of epiblast cells towards the groove. After its appearance, it is possible to identify embryo’s craniocaudal axis, ventral & dorsal aspects as well as its Rt. & Lt. sides. *Primitive node: Rounded bulge in primitive streak cephalic end with middle depression (primitive pit). *Invagination: a)Epiblast cells migrate towards the primitive groove, passing through it towards hypoblast, forming;: -Endodermal layer replacing hypoblast. -Intra-embryonic mesoderm forming embryonic disc middle layer. -Notochord in embryonic disc median region. b)Remaining epiblast layer is called ectoderm & its junction with amnion is called amnio-ectodermal junction. Finally, embryonic disc becomes formed of 3 germ layers (ectoderm, mesoderm & endoderm). *Buccopharyngeal membrane: Rounded area of fusion between ectoderm & endoderm at embryonic disc cranial part. *Cloacal membrane: Rounded area of fusion between ectoderm & endoderm at embryonic disc caudal part. *Change of shape of embryonic disc: At beginning of 3rd week, disc is oval in shape then due to spread of intraembryonic mesoderm, cranial part becomes broader than caudal part giving disc pear shaped appearance. Notochord *Def.: Temporary axial skeleton of embryonic disc. *Development: 1)Prenotochordal process; formed by invagination of solid cord cells from primitive pit. It extends cranially in midline between ectoderm and endoderm till buccopharyngeal membrane. 2)Notochordal canal; primitive pit extends into process transforming it into canal. Its roof is in contact with ectoderm, while floor is fused with endoderm. 3)Neurenteric canal; tempoary communication between amniotic cavity & yolk sac due to degeneration of canal floor together with median endoderm fused with it. 4)Notochordal plate; persisting canal roof which fuses with remaining endoderm. 5)Definitive notochord; notochordal plate becomes folded upon itself forming solid cord (definitive notochord). Endoderm regenerates so amniotic cavity & yolk sac regain their separation from each other. *Importance: a)Temporary axial skeleton of embryonic disc. b)During folding, its firmness limits head fold. c)Vertebral column is formed around it. *Fate: Vertebral column & intervertebral discs are formed around notochord which persists as nucleus pulposus inside disc. Intra-embryonic mesoderm *Its cells originate from epiblast cells migrating to primitive streak & node, then they slip through primitive groove to invaginate between ectoderm & endoderm, forming embryonic disc middle layer & transforming it into trilaminar disc (gastrulation). *It is not present at following sites; buccopharyngeal membrane, cloacal membrane, notochord site & neural tube site. * At 17th day, it is divided into paraxial, intermediate & lateral plate-mesoderm.  Embryonic period-period of organogenesis (4TH TO 8TH week of development) It is time when each of 3 germ layers of embryo gives rise to number of derivatives 1-Ectoderm derivatives Central nervous system Neural crest Otic & Other lens ectoderm placode derivatives CNS formation (Neurulation) is induced by growth factors secreted from -2 ectodermal cells strips, on both sides of Ectodermal developing notochord, through following steps: neural plate. thickenings 1)Peripheral 1)Neural plate: Thickened median ectodermal region, formed by change -Development: *During neural folds fusion, at embryo nerves. of ectodermal cells shape from cuboidal to columnar. Lies at median the 2 neural crest bands fuse together forming cranial part. region between primitive node & buccopharyngeal membrane, dorsal to median single strip, dorsal to neural tube & 2)Sensory notochord. 2 cell strips (neural crest) are present on both sides of neural plate. is covered by surface ectoderm. *Otic epithelium *Then divides into 2 longitudinal cell placode of ear, nose, 2)Neural groove: Median depression in neural plate with 2 elevated columns on neural tube dorsolat. aspect. forms otic eye & skin neural folds on both sides. Neural crests are present on both sides of neural -Derivatives: 1)Ganglia (sensory, vesicle then epidermis. folds. internal ear. 3)Fusions: Between 3structures as follows; sympathetic & parasympathetic). 2)Cells (Schwann, glial, melanoblast & 3)Pituitary a)Neural folds fuse together, starting at neck & extending in cranial & iris pigmented epithelium). *Lens gland. caudal directions forming neural tube. Last parts to be fused are cranial placode 3)Adrenal medulla, arachnoid & pia mater. 4)Ant. part neuropore (closes at 25th day) & caudal neuropore (closes at 27th day). forms Neural tube forms brain inside skull & spinal cord in vertebral canal. 4)Some skull bones & teeth enamel. oral cavity eye lens. 5)Septum between ascending aorta & & lower part b)Neural crest strips fuse together dorsal to neural tube, then it pulmonary trunk. anal canal. splits into 2 columns dorsolateral to neural tube. c)Rest of ectoderm fuse together covering neural crest & neural tube, forming surface ectoderm. 2-Intraembryonic mesoderm development *Def.: Layer separating ectoderm & endoderm. *Origin: From epiblast cells that invaginate through groove of primitive streak & primitive pit. *Site: Between ectoderm & endoderm except in following sites; buccopharyngeal membrane, cloacal membrane & median region which is occupied by developing notochord & neural tube. *Differentiation: At 17th day, it is divided into 3 parts; 1-Paraxial mesoderm: Present on both sides of notochord & neural tube. 2-Intermediate mesoderm: Present between paraxial & lat. plate mesoderm. 3-Lateral plate mesoderm: Most lateral part. N.B.: Cells from primitive streak cranial part form paraxial mesoderm, cells from primitive streak middle part form intermediate mesoderm & cells from primitive streak caudal part form lateral plate mesoderm. Paraxial mesoderm Intermediate Lateral plate mesoderm mesoderm *Part on both sides of notochord & neural tube. *Part lat. to intermediate mesoderm. *Segmentation: It is divided transversely into segments (somites). It Part between par- *Lat. plate mesoderm on both sides are continuous together starts at occipital region & extends caudally. Smaller segments are axial & lat. plate cranial to buccopharyngeal membrane. It is continuous st present cephalic to 1 occipital somite (somitomeres). mesoderm. Partially with extra-embryonic mesoderm at disc margin. *Somites: Segmented masses of paraxial mesoderm. segmented & forms *Intra-embryonic coelom: *Segmentation time: 1st pair appears in 20th day, then 3 pairs are urogenital system. a)Horse shoe cavity formed in lat. plate mesoderm. Its formed per day till 30th day (somite period), then continues in caudal ends communicate with extra-embryonic coelom at slower rate till 35th or 40th day. disc margin. It is divided into; *Number: 42 – 44 somites pairs. 1-Pericardial cavity in coelom median cranial part. *Embryo age determination(Somite period): 2-Peritoneal canals in coelom lat. part. Age in days = Number of somites - 1 + 20 3-Pleural cavities between pericardium & peritoneal canals. 3 b)It splits lat. plate mesoderm into: *Regional classification: 4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral & 8 – 10 coccygeal somites. 1-Somatopleuric (somatic) mesoderm; mesoderm in *Somites differentiation: Each somite is divided obliquely into; contact with ectoderm. Forms connective tissue of body 1)Sclerotome: Ventromed. part of somite which migrates med. to anterolat., parietal pleura, pericardium & peritoneum. surround notochord forming vertebral bodies & intervertebral 2-Splanchnopleuric (splanchnic) mesoderm; discs & surrounds neural tube forming vertebral neural arch. mesoderm in contact with endoderm. Forms gut & respiratory 2)Dermomyotome: Dorsolat. part of somite which is subdivided into; tract smooth muscles & connective tissue, cardiac muscles a)Dermatome: Forms skin dermis while epidermis is formed of ectoderm. as well as visceral pleura, pericardium & peritoneum. b) Myotome: Divides into dorsal part which forms body back N.B.: 1-Cardiogenic area is splanchnic mesoderm related skeletal muscles & ventral part which forms skeletal muscles of to pericardium. anterolat. body aspect & limbs. 2-Septum transversum is mesoderm mass cranial to N.B.: Each spinal n. divides into dorsal & ventral rami to supply pericardium (before folding) &caudal to it (after folding). myotomes divided parts. 3-Endoderm derivatives a)Lining epithelium of : 1-Digestive system except its beginning & end. 2-Respiratory tract. 3-Most of urinary bladder & urethra. 4-Tympanic cavity & Eustachian tube. b)Glandular epithelium: Parenchyma of liver, pancreas, thyroid, thymus, tonsils (palatine & nasopharyngeal), parathyroid glands. Folding *Def.: Process by which embryonic disc becomes folded upon itself. *Time: Starts at 3rd week end & completed at 4th week end. *Types: 1)Cephalo-caudal folding; forming head & tail folds. 2)Lat. folding; folding of embryonic disc sides. *Causes: 1)Increase of embryonic disc longitudinal length due to neural tube & somites growth leads to cephalo-caudal folding. 2) Amniotic cavity expansion leads to folding in all directions. *Limitations of head & tail folds: Head fold is limited by relatively firm notochord cranial end, while tail fold is limited by relatively firm primitive streak. *Steps (results): 1-Amniotic cavity expansion leads to primitive umbilical ring formation by ventral shifting of amnio-ectodermal junction towards endoderm. The ring contains connecting stalk, allantois & vitelline duct. 2- Embryonic disc gradually bulges in amniotic cavity, embryo becomes completely surrounded by amniotic cavity bathing in amniotic fluid. 3-Embryonic disc changes into cylindrical shape which has a body cavity & ectoderm becomes on embryo outer surface. 4-Embryonic disc cranio-caudal elongation by neural tube & somites growth leads to cephalo-caudal folding with head & tail folds formation. 5-Part of yolk sac is incorporated inside folded embryo leading to gut formation which is lined with endoderm; foregut in head fold, midgut in middle & hindgut in tail fold. 6- Formation of definitive yolk sac which is yolk sac part remaining outside abdomen in umbilical cord. Midgut is connected to definitive yolk sac by vitelline duct. 7- Peritoneal canals of intraembryonic coelom surround gut with subsequent mesenteries formation. 8- Formation of forebrain bulge in head fold which is separated from pericardial bulge by stomodeum. Buccopharyngeal membrane separates stomodeum from foregut. 9- Reversal of position; a)Heart & pericardium become cranial to septum transversum (before folding, septum transversum was most cranial). b)Connecting stalk & allantois become ventral & cranial to cloacal membrane instead of being most caudal before folding. Fetal membranes Structures developed from zygote but do not share in part formation of embryo, they are: 1-Chorion & placenta 2-Amnion. 3-Umbilical cord 4-Yolk sac. 1-Chorion *Def.: Chorionic vesicle wall. *Formation: At 12th day, extra-embryonic mesoderm is formed on cyto- trophoblast inner aspect. Chorionic vesicle is formed when extra-embryonic mesoderm spaces fuse forming extra-embryonic coelom (chorionic cavity) with subsequent mesoderm division into: a)Somatic mesoderm which lines cyto- trophoblast & covers amniotic cavity b)Splanchnic mesoderm which covers yolk sac. *Layers: From external to internal; 1-Syncytiotrophoblast. 2-Cytotrophoblast 3-Extraembryonic somatic mesoderm. *Chorionic villi: See before. 2-Placenta *Def.: Organ through which materials exchange occurs between maternal & fetal blood. *External features (full term placenta): -Shape: Disc shape -Weight: 500 – 600 gm. -Diameter: 15 – 20 cm -Thickness: 3 cm. -Site: Mostly in upper segment of uterine cavity post. wall, near fundus. -Surfaces (2): a)Fetal surface; surface facing fetus. Smooth & covered with transparent amnion, umbilical cord is attached near its center. b)Maternal surface; surface lying in contact with uterine wall internal surface. Shows 15 – 20 elevations (cotyledons) which are separated from each other by grooves & covered by thin layer of decidua basalis. *Formation (2 main parts): 1-Maternal; decidual plate (decidua basalis). 2-Fetal; chorionic plate (chorion frondosum). *Structure: Placenta is composed of; 1)Chorionic plate (from external to internal): a)Amnion b)Somatic extraembryonic mesoderm. c)Cytotrophoblast d)Syncytiotrophoblast. 2)Decidual plate (from internal to external): a)Syncytiotrophoblast (lines intervillous space). b)Cytotrophoblastic shell c)Decidua basalis. 3)Chorionic villi: Tertiary villi of chorion frondosum, composed of following; a)Syncytiotrophoblast (outer layer) b)Cytotrophoblast. c)Somatic extraembryonic mesoderm d) Fetal blood vessels endothelium. Parts of chorionic villi: a)Stem (anchoring) villi; villous extending between chorionic & decidual plates. b)Floating (absorbing or free) villi; side branches from stem villi floating in maternal blood of intervillous spaces, allowing food material & gases exchange between fetal & maternal blood. 4)Intervillous spaces: Intercommunicating spaces separating stem villi & extending from chorionic plate to decidual plate. Maternal arterioles & venules open into spaces through decidual plate. 5)Placental (decidual) septa: -Extend from decidual plate to intervillous spaces cavity, appearing during 4th & 5th months. They are incomplete septa that do not extend to chorionic plate. -Each septum is composed of decidua basalis core, covered with cytotrophoblast & syncytiotrophoblast. Cotyledons on maternal surface are separated by grooves corresponding to placental septa inwards extension. *Placental circulation: Blood circulation inside placenta & is composed of: 1)Maternal part (maternal blood circulation); -Arterial blood flows to intervillous spaces through 80 – 100 decidual arterioles. Maternal blood flows back towards decidual plate to leave intervillous space through maternal venules. -Full term placenta contains about 150 ml maternal blood, changed 3 – 4 times/min. 2)Fetal part (inside fetal blood vessels);-Umbilical arteries leave fetal abdomen through umbilical cord, reaching placenta fetal surface where they branch & enter tertiary villi. - After exchange between fetal & maternal blood, fetal blood is carried through Lt. umbilical vein to fetal heart where it is distributed to fetus body. *Placental barrier (membrane): -Membrane separating fetal blood (inside tertiary villi) & maternal blood (in intervillous spaces). -Early placental barrier is composed of following layers: a) Fetal blood vessels endothelium b)Somatic extraembryonic mesoderm. c)ytotrophoblast d)Syncytiotrophoblast. -Late placental barrier (from 4th month) is composed of: a) Fetal blood vessels endothelium b)Syncytiotrophoblast. So, placental membrane becomes thinner in pregnancy 2nd half to allow rapid nutrition & gases exchange, to give adequate supply to larger fetus. -Functions of barrier: 1-Separates fetal & maternal blood. 2-Permits gaseous, nutritive & waste products exchange. 3-Prevents passage of bacteria & most of viruses (except Human Immuno- deficiency Virus (HIV), poliomyelitis, rubella, cytomegalovirus & measles). 4-Prevents passage of most toxic material & most of maternal hormones (except some synthetic hormones e.g. progestin & diethylstilbestrol). *Functions of placenta: 1-Exchange of metabolic products (transmission of nutritive substances from maternal to fetal blood & in opposite direction waste products are transmitted from fetal to maternal blood). 2-Exchange of gases; giving oxygen to fetus & receiving CO2 from fetal blood. 3-Transmission of maternal antibodies to fetus starting from 14th week, so fetus will gain immunity since this time. 4-It has endocrine function as it produces: a)Progesterone which maintains pregnancy endometrium. b)Estrogen which stimulate uterine growth & mammary gland development. c)Human chorionic gonadotropins (HCG) which maintains corpus luteum till 4th month & used to detect pregnancy. D)Somatomammotropin gives fetus priority on maternal blood glucose & promotes breast development. 5-Placenta has a protective role as it prevents passage of bacteria and most of viruses from mother to fetus. 6-Placenta has excretory function as it gets rid of fetal urea & creatinine. *Abnormalities of Placenta: 1-In position (placenta previa); due to embryo implantation in uterus lower segment. Types of placenta previa; a)Placenta previa parietalis: Placenta margin is near internal os. b)Placenta previa marginalis: Placenta margin covers internal os. c)Placenta previa centralis: Placenta central part covers internal os. 2-In shape: bilobed or trilobed. 3-In number: a)Twin placenta; 2 identical placentae with 2 umbilical cords. b)Accessory placenta; main placenta is accompanied with small placenta. 4-In umbilical cord attachment: a)Velamentous placenta; umbilical cord is attached to placenta through membranes. b)Battle door placenta; cord is attached to placenta margin. 5-In diameter: Placenta membranacea (thinner & wider placenta). 6-In infiltration: Deep infiltration of placenta (placenta accreta) to myometrium (increta) or to covering peritoneum (percreta). 3-Amnion *Def.: Amniotic cavity wall of. After folding amniotic cavity surrounds fetus. *Formation of amniotic cavity: -It appears at 8th day within embryoblast cells. Separates amnioblasts (adjacent to cytotrophoblast) & epiblast (adjacent to hypoblast). -Amnioblast cells start amniotic fluid production. In 3rd week, Junction between ectoderm & amnion is called amnio-ectodermal junction. *Expansion of amniotic cavity: Leads to; -Amnioectodermal junction is shifted ventrally after folding & surrounds primitive umbilical ring. With more expansion, amnion surrounds umbilical cord & covers placenta fetal surface. - At 3rd month, amnion comes in contact with chorion forming amniochorionic membrane with chorionic cavity obliteration. By 3rd month end, amnio- chorionic membrane covered with decidua capsularis comes in contact with decidua parietalis, obliterating uterine cavity. *Amniotic fluid:a)Clear watery fluid mainly composed of water, electrolytes, proteins, carbohydrates, lipids , phospholipids & urea. b)Partially produced by amnioblasts but primarily derived from maternal blood by osmosis through amnion. After renal development, fetal urine is added daily to amniotic fluid starting from 5th month. *Volume of amniotic fluid: Reaches 1.0 – 1.5 liter starting from 37th week till birth. *Amniotic fluid & stem cells: Recent studies show that amniotic fluid contains considerable quantity of stem cells. These cells are pluripotent & able to differentiate into various tissues, including brain, liver & bone. *Functions of amniotic fluid: a)At early pregnancy: 1-Acts as shock absorbent protecting fetus against external trauma. 2-Acts as heat insulator keeping constant fetal temperature. 3-Prevents embryo adhesion to uterus wall. 4-Prevents adhesion of fetal parts together e.g. limb to body. B)At late pregnancy: 1-Gives space for fetal movements which is essential for fetal muscle development. 2-Gives space for urine accumulation. 3-At 5th month beginning, fetus starts to swallow amniotic fluid & this helps him to learn suckling. C)During delivery: 1-Protects fetus against uterine contractions. 2- Amniotic sac forebag helps gradual cervical canal dilatation. 3-Forebag rupture is sign of labor start. 4-Sterile amniotic fluid washes vagina just before fetus passage. *Amniotic fluid abnormalities: a)Polyhydramnios; increase of amniotic fluid volume to be more than 2 liters at full term. Causes: a)Unknown cause in 35 % of cases b)Maternal diabetes c)Congenital malformation as esophageal atresia which interferes with normal fetal swallowing. d)Congenital malformation of central nervous system as anencephaly. b)Oligohydramnios; decrease of amniotic fluid volume to be less than 400 ml at full term. Causes: May result from renal agenesis or urinary tract obstruction. c)Amniotic sac premature rupture; rupture of sac before uterine contractions start. Most common cause of preterm labor. No cause could be identified for this condition.  4-Umbilical cord *Def.: Cord connecting fetus & placenta. *Morphology: a)Attachments; extends between fetal surface of placenta & ventral aspect of fetal abdominal wall. b)Length; 50 – 60 cm. c)Structure; contains 2 umbilical arteries & 1 umbilical vein, embedded in Wharton’s jelly & covered with amnion. *Functions: 1-Contains umbilical vessels which transmit fetal blood between fetus & placenta. 2-Allows fetus free mobility. *Development: a) Primitive umbilical ring formation; amniotic cavity expansion leads to embryonic disc folding (during 4th week) with ventral shifting of amnioectodermal junction & subsequent primitive umbilical ring formation which contains: -Connecting stalk with allantois & umbilical vessels. -Vitelline duct & vitelline vessels. b) Primitive umbilical cord formation ; amniotic cavity expansion leads to collection of primitive umbilical ring contents inside amnion sheath, forming primitive cord which contains: -Connecting stalk, allantois remnant & umbilical vessels. -Definitive yolk sac, vitelline duct & vitelline vessels. -At 6th week, intestinal loop herniates in umbilical cord (physiological hernia). c) Definitive umbilical cord formation ; intestinal loop returns to abdominal cavity by 3rd month. Obliteration of vitelline duct, allantois & extra- embryonic parts of vitelline vessels. Degeneration of Rt. umbilical vein with persistence of Lt. vein. Wharton’s jelly formation from connecting stalk mesoderm. *Abnormalities: 1-Short cord; leads to fetus movements limitations & placenta premature separation. 2-Long cord; may encircle fetus neck. 3-Congenital umbilical hernia (omphalocele); cord contains intestine coils which failed to return to abdominal cavity. 4-One umbilical artery degeneration with persistence of other artery. 5-Umbilical cord abnormal attachment; may be attached to placenta margin (battledore) or through membranes (velamentous). 6-True knots; leads to umbilical vessels obstruction with subsequent fetus death. False knots are sites where umbilical vessels become tortuous without interrupting blood flow.  5-Yolk sac *Def.: Sac replacing blastocele of blastocyst. *Development: 3 stages; 1)Primary (primitive) yolk sac; at 9th day, Heuser’s membrane is developed from hypoblast cells & migrates to line blastocele. 2)Secondary yolk sac; formed at 13th day due to following changes: -New cells generations from hypoblast line Heuser’s membrane. -Reduction of yolk sac size due to pinching off a part known as exocoelomic cyst. - Allantois formation, which is diverticulum extending from yolk sac caudal part inside connecting stalk. 3)Defenitive yolk sac; during 3rd week, hypoblast layer is replaced by endodermal layer. After folding (during 4th week), yolk sac shares in gut formation & remaining part in primitive umbilical cord is called definitive yolk sac, which is connected to mid-gut by vitello-intestinal (vitelline) duct. *Fate: Definitive yolk sac & vitelline duct gradually reduce in size & finally degenerate. *Functions: a) Gut formation; endodermal lining of yolk sac shares in formation of mucosa of foregut, midgut & hindgut after embryonic disc folding. b)Formation of urinary bladder part; from allantois proximal part. c) Primordial germ cells formation; At 2nd week, epiblast cells migrate to caudal part of yolk sac wall forming primordial germ cells. d)Vitelline vessels; develop in mesoderm around vitelline duct. Intra- embryonic parts of vitelline vessels will remain forming gut arteries & veins, while extraembryonic parts disappear. e)Blood cells; develop in yolk sac mesoderm in early pregnancy. Fetal period Period from beginning of 9th week till birth. It is characterized by maturation of tissues & organs as well as body rapid growth. Fetus length is usually indicated as crown-rump length (CRL) (sitting height) or as crown-heel length (CHL), measurement from skull vertex to heel (standing height). These measurements are correlated with fetus age in weeks.  Age (weeks) C-R length (cm) Weight (grams) 9 - 12 5–8 10 - 45 13 - 16 9 - 14 60 - 200 17 -20 15 - 19 250 - 450 21 - 24 20 - 23 500 – 820 25 – 28 24 – 27 900 – 1300 29 – 32 28 – 30 1400 – 2100 33 – 36 31 – 34 2200– 2900 37 – full term 35 – 36 3000– 3400 *Relative size of head to body: -At 3rd month beginning, head is 1/2 CR length. -At 5th month beginning, head is 1/3 CH length. -At birth, head is 1/4 CH length. *Changes in external features: -Face becomes human looking during 3rd month. -Limbs become longer at 3rd month. -External genitalia are differentiated at 3rd month end. -Lanugo hair covers fetus starting from 4th month. -Fetus Skin is covered by fatty substance (vernix caseosa) at 5th month. -Skin is wrinkled till 6th month end due to absence of subcutaneous fat. -Testes descend to scrotum just before birth. *Fetal movements: Clearly recognized since 5th month. *Birth Time: Pregnancy duration is about 280 days (40 weeks) starting from 1st day of last menstruation or more accurately 266 days (38 weeks) after fertilization. Twins *Def.: Giving birth to more than one baby. *Types: Dizygotic Monozygotic (identical) (fraternal) twins Formation of 2 zygotes by Cause simultaneous ovulation of Splitting of fertilized ovum at variable stages of development. 2 oocytes & fertilization by 2 sperms.  Commonest type, represents Incidence 0.7 – 1.1% of total births. 0.3 – 0.4 % of total births -Offspring are not identical -Offspring are identical in shape and sex. Features in shape & may be of -Fetal membranes are variable according to splitting stage.  same or different sex. a)Morula splitting: Morula divides into 2 morulae which develop into 2 separate balstocysts. Each embryo has its own -Each embryo implants amnion, chorion & placenta. separately. b)Inner cell mass splitting of early blastocyst: Single blastocyst which has 2 inner cell masses. Each embryo has its -Each embryo develops its own amnion. Both embryos have a common chorion & placenta. own amnion, chorion & c)Embryonic disc splitting of late blastocyst: placenta. Single blastocyst which has 2 embryonic discs. Both embryos have a common amnion, chorion & placenta. *Anomalies: 1)Siamese (fused) twins: Occurs due to incomplete split of embryonic disc. Twins may be fused at head (craniopagus), at thorax (thoracopagus) or pelvis (pygopagus). Success of surgical separation depends on fusion site & organs in common between twins. 2)Twin defects: Twins may suffer from increased incidence of prematurity, low birth weight or high mortality rate. Birth defects Structural abnormalities and / or functional disorders present at birth. Caused by environmental or genetic factors acting independently or together. *Risky gestational period: Most sensitive time is embryonic period (3rd to 8th week). During fetal period (9th week to full term), risk for gross structural defects are decreased, but organ systems may still be affected. *Factors responsible for birth defects: See table;  Environmental factors (teratogens) Chromosomal abnormalities Effect varies according to; developmental stage at exposure time, dose & exposure duration. 1-Infectious agents: -Viruses; as German measles, cytomegalovirus, herpes 1-Numerical: Offspring has abnormal chromosomal number, could be simplex, varicella & HIV -Bacteria; as Syphilis -Parasites; as toxoplasma. autosomal or in sex chromosomes. 2-Radiations: Ionizing radiation (x-ray & gamma rays) has teratogenic I-Autosomal: a)Trisomy 21 (Down syndrome or mongolism): There effects because; they kill rapidly proliferating cells & lead to genetic is an extra chromosome 21 so chromosomal number is 45 + XX or XY. It occurs due to alteration of germ cells with subsequent fetal malformations. non-disjunction of chromosomes 21 during 1st meiotic oocyte division. Child 3-Drugs & chemicals: Most of drugs have teratogenic effects especially possibility with Down syndrome increases with mother age increase. in 1st 3 months. Alcohol & nicotine have also teratogenic effect. 4-Maternal causes: a) Congenital malformations incidence is 3 – 4 times Mongol child has specific facial features with mental retardation. b)Trisomy 13, 15, 17 or 18: Less common, infant suffers from many higher in diabetic mother offspring. b)Iodine deficiency in maternal diet leads to baby cretinism. congenital anomalies & usually dies by age of 2 months after birth. II-Sex-chromosomes: a)Klienfelter syndrome (44 + XXY): Occurs c)Obese mother give birth to babies with neurological defects. due to non-disjunction of X-chromosomes during oocyte division. Male d)Pregnant mothers above 40 years old have higher possibility to give child suffers from gyneacomastia & infertility. birth to child suffering from Down syndrome. b)Turner syndrome (44+X0): Occurs due to non-disjunction of sex e)Mothers with cyanotic heart disease & those living in high altitude may chromosomes during division of either male or female gametes. A female child suffers from webbed neck & infertility due to ovaries agenesis. give birth to small size infants with no gross congenital anomalies. 2-Structural chromosomal abnormalities: Result from breaking of f)Hyperthermia (increased body temperature) either caused secondary to a chromosome due to exposure to viruses, radiations or drugs. bacterial infections or externally as exposure to hot sun or sauna may a)Cri-du-Chat syndrome: There is partial deletion of short arm of affect neurulation leading to anencephaly or spina bifida. chromosome 5. Child suffers from cat like cry, microcephaly, mental 5-Paternal causes:a) Exposure to chemicals & radiation can cause male retardation & congenital heart disease. germ cells mutations. b)Angelman syndrome: There is partial deletion of chromosome 15 b) Advanced age may lead to male gametes chromosomal defects with long arm. Child suffers from mental retardation, inability to speak, poor subsequent offspring anomalies e.g. Down syndrome. motor development & prolonged laughter period. *Prevention of birth defects: Many birth defects can be prevented. For example, supplementation of salt or water supplied with iodine, eliminates mental retardation and bone deformities resulting from cretinism. Folate supplementation lowers neural tube defects incidence, such as spina bifida & anencephaly, also reduces hyperthermia-induced abnormalities risk. Avoidance of alcohol & other drugs during all pregnancy stages reduces birth defects incidence. *Prenatal diagnosis of fetal malformations: To assess fetal growth & development in utero, routine ultrasonography examination, maternal serum screening (alpha feto-protein level), amniocentesis (for genetic analysis of sloughed fetal cells) & chorionic villus sampling (placenta sample for genetic analysis) should be performed when there is suspicious fetal malformation. Fetal therapy Fetal transfusion Fetal medical treatment Fetal surgery Stem cells therapy Gene Therapy In cases of fetal Treatment of infections, Because of advances in ultrasound Stem cells have two important characteristics It is an experimental anemia produced fetal cardiac arrhythmias & surgical procedures, operating on which distinguish them from other types of technique which uses by maternal & other medical problems fetuses has become possible. It could cells. First, they are unspecialized cells which genes to treat or antibodies or is usually provided to be done either by open fetal surgery renew themselves for long periods through prevent disease. In other causes, mother & reaches fetus or by minimally invasive fetoscopic cell division. Second is that under certain future, it may allow fetus blood through maternal blood surgery (fetendo) which uses small physiologic or experimental conditions, they managing disorder transfusion can after placenta crossing. can be induced to become cells with special by; replacing mutated incisions & guided by fetoscopy & be performed. However in some cases, sonography. However, because of functions such as beating cells of heart gene, inactivating a Ultrasound is agents may be administered risks to mother, infant & subsequent muscle or insulin- producing cells of pancreas. mutated gene or used to guide to fetus directly by pregnancies, procedures are only Scientists primarily work with two kinds of introducing new gene. needle insertion intra-muscular injection performed in centers with well-trained stem cells from animals & humans; embryonic into umbilical into gluteal region or teams & only when there are no stem cells & adult stem cells. Because fetus cord v. & blood via umbilical vein. reasonable alternatives. It is indicated does not develop any immunocompetence is transfused in cases of repairing congenital before 14 weeks gestation, it may be possible to directly into fetus. diaphragmatic hernia, congenital transplant tissues or cells before this time heart defects or even neural tube defects. without rejection. Research in this field is focusing on hematopoietic stem cells for immune- deficiency & hematologic disorders treatment.