Introduction
Molecular analysis of oocyte, sperm, zygote, and blastocyst has recently focussed on examining the specific genes that are being either activated or inactivated
as part of the developmental program. Tools such as microarray analysis have begun to make an impact in this area of research, where at any specific
developmental stage, the whole genome expression profile can be monitored. Note, some material in this section of notes will overlap with the second week (blastocyst) of development.
The first week of human development begins with
fertilization of the egg by sperm forming
the zygote, followed by early cell division forming
the blastocyst. This page discusses molecular
events that drive this process of development
during the first week.
A recent study (Minoru et al.,
2000) using large scale cDNA analysis has
identified, in the mouse, 798 new genes that are
expressed prior to implantation. While this does
not specifically identify what these genes
functions are, it does provide a key to begin
analysis of specific gene expression required in
the preimplantation mammalian/human blastocyst.
Zygote with 2 pronuclei
Dr S. J. DiMarzo
Page Links: Introduction | Some Recent Findings | Development Overview |
WWW Links | References | Glossary
Some Recent Findings
Li SS, Liu YH, Tseng CN, Singh S.
Analysis of gene expression in single human oocytes and preimplantation embryos.
Biochem Biophys Res Commun. 2006 Feb 3;340(1):48-53.
Salpekar A, Huntriss J, Bolton V, Monk M.
The use of amplified cDNA to investigate the expression of seven imprinted genes in human oocytes and preimplantation embryos.
Mol Hum Reprod. 2001 Sep;7(9):839-44.
Heikinheimo O, Lanzendorf SE, Baka SG, Gibbons WE.
Cell cycle genes c-mos and cyclin-B1 are expressed in a specific pattern in human oocytes and preimplantation embryos.
Hum Reprod. 1995 Mar;10(3):699-707
Gene Expression
Studies in early gene expression began with the isolation of messenger RNA from oocytes mainly, as sperm was thought to be translationally inactive (recent work suggests otherwise).
From early 2000 onward microarray analysis has been making inroads to our overall understanding of gene expression, identifying those initial genes required for
early blastocyst development and implantation (week 2).
Minoru et al., (2000) using large scale cDNA analysis has identified in the mouse 798 new genes that are expressed prior to implantation. While this does not specifically identify what these
genes functions are, it does provide a
key to begin analysis of specific gene
expression required in the
preimplantation mammalian/human
blastocyst. Minoru S, et al.
Large-scale cDNA analysis reveals phased gene
expression patterns during preimplantation mouse
development. Development 127, 1737-1749
(2000)
Development Overview
- Human Embryology (2nd ed.) Larson Ch1
p1-32
- The Developing Human: Clinically Oriented
Embryology (6th ed.) Moore and Persaud
- Before we Are Born (5th ed.) Moore and
Persaud Ch Ch 2 p14-33
- Essentials of Human Embryology Larson Ch1
p1-16
- Human Embryology Fitzgerald and Fitzgerald
Ch2 p8-14
- Additional References- Selected
- Search PubMed-
Medline
Fertilization and Early Development Overview
(Text)
- Gamete formation
- egg formation-oogenesis
- sperm formation- spermatogenesis
- Fertilization
- sperm and egg migration
- sperm- activation, binding, acrosome
reaction
- egg- 2nd meiotic division, cortical
reaction
- Formation of the Zygote
- male and female pronuclei
- first mitotic division
- sex determination
- Formation of the Blastocyst
- Female Reproductive
- Early cell division
- Gamete formation- Oogenesis
- process of oogonia mature into oocytes
(ova, ovum, egg)
- all oogonia form primary oocytes before
birth
- maturation of preexisting cells in the
female gonad- ovary
- humans usually only 1 ovum released (IVF-
superovulation)
- oocyte and its surrounding cells =
follicle
- primary -> secondary -> ovulation
releases
- Ovary- whole t/s
- Menstrual Cycle
- Oogenesis- preantral follicle
- Primary Oocyte
- arrested at early Meiosis 1
- diploid: 22 chromosome pairs + 1 pair
X chromosomes (46, XX)
- autosomes and sex chromosome
- Oogenesis- antral follicle
- 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
- 2nd Meiotic Division
- Ovulation
- Hypothalmus (GRH) -> Pituitary FSH and
LH -> ovary
- GRH- gonadotropin releasing hormone
- FSH- follicle stimulating hormone
- LH- lutenizing hormone
- release of the secondary oocyte and
formation of corpus luteum
- secondary oocyte encased in zona
pellucida and corona radiata
- Ovulation- ampulla movement
- Ovulation- follicle
- Zona Pellucida
- glycoprotein shell ZP1, ZP2, ZP3
- 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
- Corona Radiata
- granulosa cells and extracellular
matrix
- protective cells for egg during
transport
- cells are also lost duringtransport along
oviduct
- nutrition
- Testis- anatomy
- 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
- Maturation involves meiosis and
spermeogenesis
- Seminiferous Tubule
- Spermatogenesis- Meiosis
- meiosis is reductive cell division
- 1 spermatagonia (diploid) = 4 sperm
(haploid)
- 46, XY (also written 44+XY)
- Spermiogenesis
- Spermatogenesis- spermeogenesis
- cell shape change round spermatids ->
elongated sperm
- loose cytoplasm
- Transform golgi apparatus into acrosome
(in head)
- Organize microtubules for motility (in
tail, flagellum)
- Segregate mitochondria for energy (in
tail)
- Spermiogenesis
- Ejaculate
- 3.5 ml, 200-600 million sperm
- Oligospermia (Low Sperm Count)
- less than 20 million sperm after 72 hour
abstinence from sex
- Ejaculate
- By volume <10 % sperm
- Accessory Glands
- 60 % seminal vesicle
- 10 % bulbourethral
- 30 % prostate
- Fertilization-sperm and egg migration
- Sperm migration
- deposited in vagina
- have approximately 24-48h to
fertilize
- migrate through cervix into uterus
- from uterus into oviduct (=uterine horn,
fallopian tube)
- Egg migration
- following ovulation from ovary into
fimbria
- then into oviduct
- Fertilization Site
- Fertilization usually occurs in first 1/3
of oviduct
- Fertilization can occur outside
oviduct
- associated with ectopic pregnancy
- In virto Fertilization- IVF, GIFT,
ZIFT....
- the majority of fertilized eggs do not go
on to form an embryo
- Fertilization- Sperm
- capacitation
- removal of glycoprotein coat and seminal
proteins
- alteration of sperm mitochondria
- binding
- ZP3 acts as receptor for sperm
- acrosome reaction
- exyocytosis of acrosome contents (Ca
mediated)
- 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
- Fertilization Figure
- Fertilization- Egg
- sperm membrane fusion
- causes depolarization of egg
membrane
- primary block to polyspermy
- Cortical reaction
- IP3 pathway elevates intracellular
Calcium
- exocytosis of cortical granules
- enzyme alters ZP3 so it will no longer
bind sperm plasma membrane
- 2nd meiotic division
- completion of 2nd meiotic division
- forms second polar body
- Egg Cortical Reaction 1
- Egg Cortical Reaction 2
- Egg Cortical Reaction 3
- Formation of the Zygote
- male and female pronuclei
- 2 nuclei approach each other
- nuclear membranes break down
- DNA replicates
- first mitotic division
- sperm contributes centriole which
organizes mitotic spindle
- Sex Determination
- based upon whether an X or Y carrying
sperm has fertilized the egg
- should be 1.0 sex ratio
- is actually 1.05, 105 males for every 100
females.
- some studies show more males 2+ days
after ovulation
- cell totipotential
- Men- Y Chromosome
- carries sry gene
- gene activates pathway for male
gonad
-
- Women- X Chromosome
- one X chromosome in each cell has to be
inactivated.
- process is apparently random
- therefore 50% of cells have father's X,
50% have mother's X
- Cleavage of the Zygote
- cleavage of zygote forms 2
blastomeres
- cleavage with no cytoplasm synthesis
- therefore individual cell volume
decreases
- initially synchronously, then
asynchronously
- slow- centre cells, larger
- fast- peripheral cells, flattened against
zona pellucida
- Early cell division
- Formation of the Morula
- there are now 16-20 cells
- at the end of the oviduct
- ball of cells
- Formation of the Blastocyst
- Day 5
- zona pellucida lost
- broken down by uterine secretions
- compaction
- central cells now compacte
- located on a region of the wall
- Blastocyst
- blastoceol formation
- cavity formed by compaction
- fluid filled blastoceol
- Blastocyst
- Embryoblast
- Inner cell mass
- forms entire embryo
- Trophoblast
- forms the placenta
- placental membranes
References
Links: Reviews | Articles | Online Textbooks | Search Textbooks |
Search PubMed | Glossary
Search PubMed
Search Feb 2006 "oocyte gene expression" xx reference articles of which xx were reviews.
Search PubMed: term = oocyte+gene+expression
| term = blastocyst+gene+expression
PubMed
Reviews
Articles
- Khamsi
F, et al. Effects of granulosa cells,
cumulus cells, and oocyte density on in vitro
fertilization in women. Endocrine. 1999
Apr;10(2):161-6.
- Dale
B, et al. Pregnancies after activated oocyte
transfer: a new option for infertility
treatment. Hum Reprod. 1999
Jul;14(7):1771-2.
- Weigert
M, et al. The effect of smoking on oocyte
quality and hormonal parameters of patients
undergoing in vitro fertilization-embryo
transfer. J Assist Reprod Genet. 1999
Jul;16(6):287-93.
- Morita
Y, et al. Targeted expression of Bcl-2 in
mouse oocytes inhibits ovarian follicle atresia
and prevents spontaneous and
chemotherapy-induced oocyte apoptosis in vitro.
Mol Endocrinol. 1999 Jun;13(6):841-50.
- Minoru S, et al.
Large-scale cDNA analysis reveals phased gene
expression patterns during preimplantation mouse
development. Development 127, 1737-1749
(2000)
Oocyte
- Aviles
M, et al. Modifications of carbohydrate
residues and ZP2 and ZP3 glycoproteins in the
mouse zona pellucida after fertilization.
Biol Reprod. 1997 Nov;57(5):1155-63.
- Zhu
X, et al. Comparison of ZP3 protein
sequences among vertebrate species: to obtain
a consensus sequence for immunocontraception.
Front Biosci. 1999 Mar 1;4:D212-5.
Review.
- Sinowatz
F, et al. Protein-carbohydrate
interactions during fertilization. Acta Anat
(Basel). 1998;161(1-4):196-205. Review.
- Buhi
WC, et al. Oviductal regulation of
fertilization and early embryonic
development. J Reprod Fertil Suppl.
1997;52:285-300. Review.
- Driancourt
MA, et al. Control of oocyte growth and
maturation by follicular cells and molecules
present in follicular fluid. A review. Reprod
Nutr Dev. 1998 Jul-Aug;38(4):345-62.
Review.
Sperm
- Wolgemuth
DJ, et al. Genetic control of mitosis,
meiosis and cellular differentiation during
mammalian spermatogenesis. Reprod Fertil Dev.
1995;7(4):669-83. Review.
- Toshimori
K. Maturation of mammalian spermatozoa:
modifications of the acrosome and plasma
membrane leading to fertilization. Cell
Tissue Res. 1998 Aug;293(2):177-87.
Review.
- Nolan
JP, et al. Regulation of membrane
stability and the acrosome reaction in
mammalian sperm. FASEB J. 1997
Jul;11(8):670-82. Review.
- Fraser
LR. Role of fertilization promoting
peptide (FPP) in modulating mammalian sperm
function. Front Biosci. 1998 Dec
1;3:D1187-91. Review.
Sex Ratios
- James
WH. Sex ratio, coital rate, hormones and
time of fertilization within the cycle. Ann
Hum Biol. 1997 Sep-Oct;24(5):403-9.
Review.
Fertilization
- "fertilization/review"
- "fertilization/polyspermy"
- "acrosome
reaction/2years"
- "acrosome/2years"
- "fertilization/meiosis"
- "fertilization/polyspermy"
- ZP1,
ZP2,
ZP3
- Gupta-
Human zona pellucida glycoproteins:
characterization using antibodies against
recombinant non-human primate ZP1, ZP2 and
ZP3.
Some Recent Reviews
- Fertilization
- Brewis
IA, et al. Molecular mechanisms of gamete
recognition and fusion at fertilization. Hum
Reprod. 1997 Nov;12(11 Suppl):156-65.
Review.
- Aitken
RJ. The cell biology of fertilization.
Adv Exp Med Biol. 1997;424:291-9.
Review.
- Wassarman
PM. Fertilization in Animals. Dev Genet.
1999;25(2):83-86.
- Fernandez
N, et al. A critical review of the role
of the major histocompatibility complex in
fertilization, preimplantation development
and feto-maternal interactions. Hum Reprod
Update. 1999 May-Jun;5(3):234-48.
- Kupker
W, et al. Principles of mammalian
fertilization. Hum Reprod. 1998 Apr;13 Suppl
1:20-32. Review.
- Parrington
J, et al. A novel protein for Ca2+
signaling at fertilization. Curr Top Dev
Biol. 1998;39:215-43. Review.
- Wassarman PM. Mammalian fertilization:
molecular aspects of gamete adhesion,
exocytosis, and fusion. Cell. 1999 Jan
22;96(2):175-83. Review. No abstract
available.
- Wilson
NF, et al. Microvilli and cell-cell
fusion during fertilization. Trends Cell
Biol. 1998 Mar;8(3):93-6. Review.
- Buhi
WC, et al. Oviductal regulation of
fertilization and early embryonic
development. J Reprod Fertil Suppl.
1997;52:285-300. Review.
- Parrington
J, et al. A novel protein for Ca2+
signaling at fertilization. Curr Top Dev
Biol. 1998;39:215-43. Review.
- In Vitro Fertilization
- Saith
RR, et al. Relationships between the
developmental potential of human in-vitro
fertilization embryos and features describing
the embryo, oocyte and follicle. Hum Reprod
Update. 1998 Mar-Apr;4(2):121-34.
Review.
- Steptoe
PC, et al. Observations on 767 clinical
pregnancies and 500 births after human
in-vitro fertilization. Hum Reprod. 1986
Feb;1(2):89-94.
- Cameron
IT, et al. Oocyte donation: a review. Br
J Obstet Gynaecol. 1989 Aug;96(8):893-9.
Review.
- Meiosis
- Smith
KN, et al. Recombination at work for
meiosis. Curr Opin Genet Dev. 1998
Apr;8(2):200-11. Review.
- Hunt
PA, et al. Genetic control of mammalian
female meiosis. Curr Top Dev Biol.
1998;37:359-81. Review.
- Moore
DP, et al. Chromosome segregation during
meiosis: building an unambivalent bivalent.
Curr Top Dev Biol. 1998;37:263-99.
Review.
- Gebauer
F, et al. Synthesis and function of Mos:
the control switch of vertebrate oocyte
meiosis. Bioessays. 1997 Jan;19(1):23-8.
Review.
- Kleckner
N. Meiosis: how could it work? Proc Natl
Acad Sci U S A. 1996 Aug 6;93(16):8167-74.
Review.
Glossary of Terms
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