Talk:Lecture - Week 1 and 2 Development
Prior to the fertilization process commencing both the gametes oocyte (egg) and spermatozoa (sperm) require completion of a number of biological processes.
- Oocyte Meiosis - completes Meiosis 1 and commences Meiosis 2 (arrests at Metaphase II).
- Spermatozoa Capacitation - following release (ejaculation) and mixing with other glandular secretions, activates motility and acrosome preparation.
- Migration - both Oocyte and Spermatozoa.
- oocyte ovulation and release with associated cells, from ovary into fimbria then into uterine tube (oviduct, uterine horn, fallopian tube) and epithelial cilia mediated movement.
- spermatozoa ejaculation, deposited in vagina, movement of tail to "swim" in uterine secretions through cervix, uterine body and into uterine tube, have approximately 24-48h to fertilize oocyte.
- Process of oogonia mature into oocytes (ova, ovum, egg)
- all oogonia form primary oocytes before birth, therefore a maturation of preexisting cells in the female gonad, ovary
- humans usually only 1 ovum released every menstrual cycle (IVF- superovulation)
- oocyte and its surrounding cells = follicle
- primary -> secondary -> ovulation releases
Ovary- Histology - whole transverse section (cortex, medulla)
- Primary Oocyte - arrested at early Meiosis 1
- diploid: 22 chromosome pairs + 1 pair X chromosomes (46, XX)
- autosomes and sex chromosome
- Oogenesis- pre-antral then antral follicle (Graafian follicle is mature antral follicle released)
- Secondary oocyte
- 1 Day before ovulation completes (stim by LH) Meiosis 1
- haploid: 22 chromosomes + 1 X chromosome (23, X)
- nondisjunction- abnormal chromosome segregation
- begins Meiosis 2 and arrests at metaphase
- note no interphase replication of DNA, only fertilization will complete Meiosis 2
Ovulation (HPG Axis)
- Hypothalmus releases gonadotropin releasing hormone (GRH, luteinizing hormone–releasing hormone, LHRH) -> Pituitary releases follicle stimulating hormone (FSH) and lutenizing hormone (LH) -> ovary follicle development and ovulation.
- release of the secondary oocyte and formation of corpus luteum
- secondary oocyte encased in zona pellucida and corona radiata
- Ovulation associated with follicle rupture and ampulla movement.
- glycoprotein shell ZP1, ZP2, ZP3
- mechanical protection of egg and involved in the fertilization process
- sperm binding, adhesion of sperm to egg
- acrosome reaction - releases enzymes to locally breakdown
- block of polyspermy
- altered to prevent more than 1 sperm penetrating
- may also have a role in development of the blastocyst
- Links: Zona pellucida
- granulosa cells and extracellular matrix
- protective and nutritional role for cells during transport
- cells are also lost during transport along oviduct
Gamete formation- Spermatogenesis
- process of spermatagonia mature into spermatazoa (sperm)
- continuously throughout life occurs in the seminiferous tubules in the male gonad- testis (plural testes)
- at puberty spermatagonia activate and proliferate (mitosis)
- primary spermatocyte -> secondary spermatocyte-> spermatid->sperm
- Seminiferous Tubule is site of maturation involving meiosis and spermiogenesis
- Spermatogenesis- Meiosis
- meiosis is reductive cell division
- 1 spermatagonia (diploid) 46, XY (also written 44+XY) = 4 sperm (haploid); 23, X 23, X 23, Y 23, Y
- morphological (shape) change from round spermatids to elongated sperm
- loose cytoplasm
- Transform golgi apparatus into acrosome (in head)
- Organize microtubules for motility (in tail, flagellum)
- Segregate mitochondria for energy (in tail)
- By volume <10 % sperm and accessory glands contribute majority of volume (60 % seminal vesicle, 10 % bulbourethral, 30 % prostate)
- 3.5 ml, 200-600 million sperm
- Capacitation is the removal of glycoprotein coat and seminal proteins and alteration of sperm mitochondria
- Infertility can be due to Oligospermia, Azoospermia, Immotile Cilia Syndrome
- Oligospermia (Low Sperm Count) - less than 20 million sperm after 72 hour abstinence from sex
- Azoospermia (Absent Sperm) - blockage of duct network
- Immotile Cilia Syndrome - lack of sperm motility
- Fertilization usually occurs in first 1/3 of oviduct
- Fertilization can also occur outside oviduct, associated with In Vitro Fertilization (IVF, GIFT, ZIFT...) and ectopic pregnancy
- The majority of fertilized eggs do not go on to form an embryo
Fertilization - Spermatozoa
- Sperm Binding - zona pellucida protein ZP3 acts as receptor for sperm
- Acrosome Reaction - exyocytosis of acrosome contents (Calcium mediated) MBoC - Figure 20-31. The acrosome reaction that occurs when a mammalian sperm fertilizes an egg
- enzymes to digest the zona pellucida
- exposes sperm surface proteins to bind ZP2
- Membrane Fusion - between sperm and egg, allows sperm nuclei passage into egg cytoplasm
- Membrane Depolarization - caused by sperm membrane fusion, primary block to polyspermy
- Cortical Reaction - IP3 pathway elevates intracellular Calcium, exocytosis of cortical granules MBoC - Figure 20-32. How the cortical reaction in a mouse egg is thought to prevent additional sperm from entering the egg
- enzyme alters ZP3 so it will no longer bind sperm plasma membrane
- Meiosis 2 - completion of 2nd meiotic division
- forms second polar body (a third polar body may be formed by meiotic division of the first polar body)
Formation of the Zygote
- Pronuclei - Male and Female haploid nuclei approach each other and nuclear membranes break down
- chromosomal pairing, DNA replicates, first mitotic division
- Sperm contributes - centriole which organizes mitotic spindle
- Oocyte contributes - mitochondria (maternally inherited)
- based upon whether an X or Y carrying sperm has fertilized the egg, should be 1.0 sex ratio.
- actually 1.05, 105 males for every 100 females, some studies show more males 2+ days after ovulation.
- cell totipotent (equivalent to a stem cell, can form any tissue of the body)
Men - Y Chromosome
- Y Chromosome carries Sry gene, protein product activates pathway for male gonad (covered in genital development)
Women - X Chromosome
- Gene dosage, one X chromosome in each female embryo cell has to be inactivated
- process is apparently random and therefore 50% of cells have father's X, 50% have mother's X
- Note that because men only have 1 X chromosome, if abnormal, this leads to X-linked diseases more common in male that female where bothe X's need to be abnormal.
Week 1 and 2
|File:Week1_001 icon.jpg</wikiflv>|| This animation shows the first week of human development following fertilization.
- about day 5 have 2 identifiable cell types and a fluid-filled cavity (blastoceol)
- trophoblast layer - peripheral flattened cells, forms the placenta and placental membranes
- inner cell mass - embryoblast, mass of rounder cells located on one wall of the blastocoel, forms entire embryo
Blastula Cell Communication
Two forms of cellular junctions Figure 21-69. The blastula
- gap junctions, allow electrically couple cells of epithelium surrounding a fluid-filled cavity
- tight junctions, close to outer surface create a seal, isolates interior of embryo from external medium
Blastocyst Hatching - zona pellucida lost, ZP has sperm entry site, and entire ZP broken down by uterine secretions and possibly blastula secretions. Uterine Glands - secretions required for blastocyst motility and nutrition
Week 2 - Implantation
The second week of human development is concerned with the process of implantation and the differentiation of the blastocyst into early embryonic and placental forming structures.
- implantation commences about day 6 to 7
- Adplantation - begins with initial adhesion to the uterine epithelium
- blastocyst then slows in motility, "rolls" on surface, aligns with the inner cell mass closest to the epithelium and stops
- Implantation - migration of the blastocyst into the uterine epithelium, process complete by about day 9
- coagulation plug - left where the blastocyst has entered the uterine wall day 12
Normal Implantation Sites - in uterine wall superior, posterior, lateral
In humans, receptivity occurs 6 days after the post-ovulatory progesterone surge and lasts about 2 to 4 days. A similar "receptivity window" occurs following fertilization in other species: rat day 5 and mouse day 4.5. Many studies have looked into identifying markers for this receptivity period both to optimise and to block this process.
Abnormal implantation sites or Ectopic Pregnancy occurs if implantation is in uterine tube or outside the uterus.
- sites - external surface of uterus, ovary, bowel, gastrointestinal tract, mesentry, peritoneal wall
- If not spontaneous then, embryo has to be removed surgically
Tubal pregnancy - 94% of ectopic pregnancies
- if uterine epithelium is damaged (scarring, pelvic inflammatory disease)
- if zona pellucida is lost too early, allows premature tubal implantation
- embryo may develop through early stages, can erode through the uterine horn and reattach within the peritoneal cavity
- Endometrium - 3 layers in secretory phase of menstrual cycle: compact, spongy, basal
- Myometrium - muscular layer outside endometrium, contracts in parturition
- Perimetrium - tunica serosa of the uterus continuous with the peritoneal wall
- Compact - implantation occurs in this layer, dense stromal cells, uterine gland necks, capillaries of spiral arteries
- Spongy - swollen stromal cells, uterine gland bodies, spiral arteries
- Basal - not lost during menstruation or childbirth, own blood supply
- occurs initially at site of implantation and includes both cellular and matrix changes
- reaction spreads throughout entire uterus, not at cervix
- deposition of fibrinoid and glycogen and epithelial plaque formation (at anchoring villi)
- presence of decidual cells are indicative of pregnancy
Cervix - at mouth of uterus, secretes mucus (CMP), forms a plug/barrier, mechanical and antibacterial Vascular - increased number of blood vessels
The endometrium becomes the decidua and forms 3 distinct anatomical regions (at approx 3 weeks)
- Decidua Basalis at implantation site
- Decidua Capsularis enclosing the conceptus
- Decidua Parietalis the remainder of uterus
- Decidua Capsularis and Parietalis fuse eventually fuse and uterine cavity is lost by 12 weeks
Endometriosis endometrial tissue located in other regions of the uterus or other tissues. This misplaced tissue develops into growths or lesions which respond to the menstrual cycle hormonal changes in the same way that the tissue of the uterine lining does; each month the tissue builds up, breaks down, and sheds. Endometriosis
- about day 8 to 9
The outer trophoblast and inner embryoblast layers now both differentiate to form two distinct cellular layers. The trophoblast layer forms the syncitotrophoblast and cytotrophoblast layers. The embryoblast (inner cell mass) forms the epiblast and hypoblast layers. This early stage of embryo development is referred to as the bilaminar embryo.
- secrete proteolytic enzymes, enzymes break down extracellular matrix around cells
- Allow passage of blastocyst into endometrial wall, totally surround the blastocyst
- generate spaces that fill with maternal blood- lacunae
- secrete Human Chorionic Gonadotropin (hCG), hormone, maintains decidua and Corpus Luteum, basis of pregnancy diagnostic test, present in urine is diagnostic of pregnancy
- Later in development placenta will secrete hCG
MH - more information in lecture 4 and laboratory.
Human Chorionic Gonadotropin
- levels peak at 8 to 10 weeks of pregnancy, then decline and are lower for rest of pregnancy
- 0-1 week: 0-50 mIU/ml
- 1-2 weeks: 40-300 mIU/ml
- 3-4 weeks: 500-6,000 mIU/ml
- 1-2 months: 5,000-200,000 mIU/ml
- 2-3 months: 10,000-100,000 mIU/ml
- 2nd trimester: 3,000-50,000 mIU/ml
- 3rd trimester: 1,000-50,000 mIU/ml
Non-pregnant females: <5.0 mIU/ml Postmenopausal females: <9.5 mIU/ml
Twinning can be due to two separate fertilization events (dizygotic twins) or as an abnormality of a single fertilization (monozygotic twins) event during the early weeks of development.
- In dizygotic twinning the genetic material is different and implantation and placentation is also different.
- In monozygotic twinning the genetic material is initially identical and degree of twinning will depend upon the timing (early to late) from separate fetal membranes and placenta to conjoined twins.
- morula stage (diamniotic dichorionic), early blastocyst (diamniotic monochorionic), late blastocyst to bilaminar (monoamniotic monochorionic), bilaminar to trilaminar embryo (conjoined)
- Monozygotic twins are a unique research resource for comparing environmental effects on development and health.
- Congenital abnormality statistics for twins is generally increased in various conditions.
Monoygotic twins (identical) produced from a single fertilization event (one fertilised egg and a single spermatazoa, form a single zygote), these twins therefore share the same genetic makeup. Occurs in approximately 3-5 per 1000 pregnancies, more commonly with aged mothers. The later the twinning event, the less common are initially separate placental membranes and finally resulting in conjoined twins.
Table based upon recent Twinning Review.
Week 1 Human Development Overview
The following figure is from a recent study using video and genetic analysis of in vitro human development during week 1 following fertilization.
- EGA - embryonic genome activation
- ESSP - embryonic stage–specific pattern, four unique embryonic stage–specific patterns (1-4)
|Ovulation||Fertilization||Pronuclear Fusion||Week 1|
| Blastocyst Development
Early development day 3 to 6
| Blastocyst Contractions
(day 5 to 6)
| Blastocyst Hatching
(day 5 to 6)
- ↑ Judith G Hall Twinning. Lancet: 2003, 362(9385);735-43 PMID:12957099
- ↑ Connie C Wong, Kevin E Loewke, Nancy L Bossert, Barry Behr, Christopher J De Jonge, Thomas M Baer, Renee A Reijo Pera Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage. Nat. Biotechnol.: 2010, 28(10);1115-21 PMID:20890283 | Nat Biotechnol.
- The Developing Human: Clinically Oriented Embryology (8th Edition) by Keith L. Moore and T.V.N Persaud - Chapter 2
- Larsen’s Human Embryology by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 2
- Developmental Biology by Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000 Figure 11.22. The cleavage of a single mouse embryo in vitro | Figure 11.25. Mouse blastocyst hatching from the zona pellucida | Figure 11.20. Development of a human embryo from fertilization to implantation | Figure 11.24. Implantation of the mammalian blastocyst into the uterus
- Molecular Biology of the Cell 4th ed. Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002 - Fertilization | Figure 21-84. Scanning electron micrographs of the early mouse embryo | Figure 21-69. The blastula
- Molecular Cell Biology by Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999 Chapter 13. Regulation of the Eukaryotic Cell Cycle
- The Cell - A Molecular Approach by Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000 Figure 14.37. Meiosis of vertebrate oocytes
- HSTAT - In Vitro Fertilization As A Medical Treatment For Male or Female Infertility
- Human Molecular Genetics 2 Strachan, Tom and Read, Andrew P. New York and London: Garland Science; c1999 Figure 8.19. Changes in DNA methylation during mammalian development
Dr Mark Hill
| ANAT2341 Embryology S2 2011
Course Content 2011
2011 Timetable: | Embryology Introduction | Fertilization | Cell Division/Fertilization | Week 1 and 2 Development | Week 3 Development | Week 1 to 3 | Mesoderm Development | Ectoderm, Early Neural, Neural Crest | Trilaminar Embryo to Early Embryo | Early Vascular Development | Placenta | Vascular and Placenta | Endoderm, Early Gastrointestinal | Respiratory Development | Endoderm and Respiratory | Head Development | Neural Crest Development | Head and Neural Crest | Musculoskeletal Development | Limb Development | Musculoskeletal | Renal Development | Genital | Kidney and Genital | Sensory | Stem Cells | Stem Cells | Endocrine Development | Endocrine | Heart | Integumentary Development | Heart and Integumentary | Fetal | Birth and Revision | Fetal
- A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols
Cite this page:
Hill, M.A. (2013) Lecture - Week 1 and 2 Development. Retrieved June 20, 2013, from http://php.med.unsw.edu.au/embryology/index.php?title=Lecture_-_Week_1_and_2_Development
- Dr Mark Hill 2013, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G