Medical Embryology –General EmbryologyFertilization to Implantation
Langman’s Medical Embryology, 9th Ed
Chapter concepts
- The definition of the Embyrology
2.The major phases of fertilization and the site where fertilization typically occurs
3. Endometrial changes that enable implantation and the hormones that modulatethis change
4. Normal sites of implantation and the most common abnormal sites
5. Morphologic changes in the zygote that occur enroute to the uterus
6. The development roles of the inner cell mass and the outer cells mass
7. Bilaminar germ discs
Ⅰ.Definition of Embryology:
--A science which study the processes and regulations of development of human fetus.(from 1 zygote to (5-7)x1012 cells)
--Total procedure is 38 weeks, including preembryonic period: before 2 weeks
embryonic period:3-8 weeks
fetal period: after 8 weeks
Note: In general the length of pregnancy is considered to be 280 days or 40 weeks after the onset of the last menstruation, or more accurately, 266 days or 38 weeks after fertilization.
Ⅱ.Fertilization:
-Definition: the process by which the male and female gametes (sperm and ovum)
fuse unit to give rise to zygote.
-Site: in the ampullary region of the oviduct
-Condition: 1) maturation of oocyte
2) maturation of spermatozoon
3)within the female genital tract the spermatozoan shed their glycoprotein coat and seminal proteins overlying its head to unveil its acrosomal region. This process is called capacitation and takes approximately 7hrs
4)quality and quantity of spermatozoa:
•2-6 ml, 100,000,000/ml,
• <1.5 ml; or <10,000,000; abnormal sperm >30%;
or capacity for mobile< 70%
5) meeting of sperm and ovum within 24 hs
-processes of fertilization:
- Phase I - Penetration of the Corona Radiata
- Although only one will fertilize the oocyte, a collective enzymatic effort isrequired to break down the barriers that surround the oocyte.
- Phase II - Penetration of Zona Pellucida
- ZP molecule (sperm head) bind to species-specific sperm receptors ZP receptor (zona pellucide) and induce acrosome reaction. The Zona Pellucida at this stage is spongy allowing attachment of thespermatozoon and local release of acrosomal enzymes.
- Phase III - Entrance - Formation of the zygote
Following penetration of the zona pellucida the plasma membrane of thehead of a spermatozoon touches the oocyte plasma membrane and theyfuse. This propels the head, middle piece and tail into the oocyte.
- Oocytes response
1) Compaction of the zona pellucida making it impermeable (cortical reaction)
2) Completion of meiosis, second cell division, second polar body andfemale pronucleus formed.
3) Metabolic activation - probably in response to a factor carried by thespermatozoon
- Nucleus of the spermatozoon swells and becomes the male pronucleus
-The newly formed zygote undergoes DNA duplication and the first mitoticcell division occurs
- Results of Fertilization
1) Two haploid gametes have fused to create a diploid zygote
2) Genetic sex determination has occurred. Female XX, Male XY thus oocyteonly has X chromosomes to contribute, male has either an X or an Y
3) Cleavage initiated
Ⅲ. Cleavage
- Mitotic divisions of the zygote
- Increase cell numbers with a gradual decrease in cell size.
- These new daughter cells are called blastomeres
- Formation of the morula (12-16 cells)
- 3 days after fertilization the zygote has undergone 3-4 cell divisions andforms a mulberry appearing mass known as the morula
- The morula has an inner cell mass destined to become the embryo and anouter cell mass which will form the trophoblasts and ultimately theplacenta (required to support embryonic development)
- Formation of the Blastocyst
- The cells of the morula secrete fluid, which collects centrally producing acavity or cyst and is thus called a blastocyst, the cavity is called blastocoele.
- The central cavity moves the inner cell mass or embryoblast to one sidecreating polarity (embryoblast pole).
-The zona pellucida now degenerates, which disappears at the end of the fourth day.
Abnormalities in the First Week
-It is estimated that 50-60% of all fertilizations are abnormal resulting inspontaneous abortion within first two weeks (see Points to Remember in theGametogenesis handout).
Ⅳ. Implantation
- Trophoblasts overlying the embryoblast pole attach to the endometrium andbegin to invade. The endometrium further stimulates enzymes secreted by thetrophoblasts encouraging trophoblastic invasion.
The 8th Day
- Implantation
-The blastocyst sinks deeper into the endometrium with the assistance ofthe trophoblastic enzymes and the receptive endometrial stroma whichenhances the activity of these enzymes.
Sites of implantation
-The developing embryo usually implants along the anterior or posterior wall (the “X”) of the uterus near the fundus (top), however, other sites of implanation occasionally occur:
-The tubal: most common site of ectopic pregnancy, life threatening as embryo develops oviduct ruptures and oviductal artery damaged-massive bleeding
-Internal os of the cervix will cause placenta previa with potentially life threatening bleeding during the 2nd trimester and at delivery.
-Abdominal ,Ovary—rare
After implanation:
-The overlying portion of the endometrium is stretched out, forming a layer known as thedeciduas capsularis
-The portion of the endometrium lining the walls of the uterus elsewhere than at the site of attachment of chorionic vesicle is called the dedidua parietalis.
-The area underlying the chorionic vesicle is termed the deciduas basalis.
Implantation conditions:
1)endometrium is in secretory phase
2)morula reach the cavity of uterus on time
3)zona pellucide disappears in time
- Outer cell mass - Trophoblastic Differentiation
- The trophoblasts overlying the embryonic pole differentiate intocytotrophoblasts an inner layer of mitotically active mononuclear cellswhich shed cells to the outer protoplasmic mass of cells without cellboundaries known assyncytiumor syncytiotrophoblaststhat lack of mitoticactivity.
- Inner Cell Mass/Embryoblast
- Between the trophoblastsand the embryoblast fluidaccumulates forming theamniotic cavity. Cellsbetween the amnioticcavity and thetrophoblasts are calledamnioblasts.
- The inner cell massbecomes organized into two layers to collectively form the bilaminargerm disc.
- The 'top' layer, adjacent to the amniotic cavity forms columnarepithelium and is known as the epiblast layer.
- The underlying cells differentiate into a cuboidal layer known as thehypoblast and are adjacent to the blastocyst cavity now known asthe exocoelomic cavity or primitive yolk sac.
- Flattened cells lining the blastocyst cavity are known as the Exocoelomicmembrane.
The Ninth through the Twelfth Day
- Implantation
- By day 9 only a fibrin plug demarcatesthe site of implantation.
- By day 12 the implantation site iscovered by endometrium, and a slightbulge betrays the underlying gestation.
- Trophoblastic Maturation
- By day nine vacuoles form within thesyncytiotrophoblasts and fuse to formlacunar networks. (which are moreelaborate at the embryonic pole)
- Syncytial cells erode maternal vesselsand blood flows into the lacunar networkinitiating a uteroplacental circulation.
-Extraembryonic Mesoderm Formation
-A new population of cells form a loose network between the exocoelomic membrane and the cytotrophoblasts and called the extraembryonic mesoderm.
-Large cavities develop within the extraembryonic mesoderm. These cavities eventually coalesce to form the extraembryonic coelom.
-The extraembryonic coelom separates the mesoderm into extraembryonic somatic mesoderm (adjacent to the cytotrophoblasts and the amnion) and extraembryonic splanchnic mesoderm (adjacent to the exoxoelomic cavity (primitive yolk sac)
Ⅴ.End of the second week
-Trophobalstic maturation:
-cytotrophoblasts proliferate focally formed solid cell column surrounded by syncytotrophoblasts.These are called primary villi.
-Formation of the Secondary Yolk Sac
- cells of the hypoblasts proliferate and migrate along the inside of the exocoelomic membrane.
- Expansion of the extraembyronic coelom, also known as the chorionic cavity reshapes the exocollomic cavity or primitive yolk sac into a secondary yolk sac and pinches off small remnants of the primitive yolk sac or exocoelomic cysts.
- The extra-embryonic somatic mesoderm and adjacent cytotrophoblasts are collectively called the chorionic plate.
- Ultimately, the chorionic cavity nearly isolates the developing embryo and adherent cavities from the trophoblats except at the connecting stalk near the caudal region of the germinal disc adjacent the amniotic cavity.
-The Germ Disc
-By the end of the second week the germ disc consists of the two juxtaposed cells discs; the epiblasts forming the floor of the amniotic cavity and the hypoblast forming the roof of the secondary yolk sac.
Note: By the 13th day of development, the surface defect in the endometrium has usually healed.Occasionally, however, a bleeding may occur at the implanation site as a result of increased blood flow into the lacunar spaces. Since this bleeding occurs near the 28th day of the menstrual cycle,it may be confused with a normal menstrual bleeding and so cause an inaccuracy in determining the expected delivery date.