|Embryology - 28 Feb 2017 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Objectives
- 4 Movies
- 5 Fertilization Preparation
- 6 Oogenesis
- 7 Menstrual Cycle
- 8 Ovulation (HPG Axis)
- 9 Zona Pellucida
- 10 Corona Radiata
- 11 Gamete formation- Spermatogenesis
- 12 Ejaculate
- 13 Fertility Window
- 14 Fertilization Site
- 15 Spermatozoa - Oocyte Interaction
- 16 Formation of the Zygote
- 17 Sex Determination
- 18 Fertilization Protein Changes
- 19 Abnormalities
- 20 References
- 21 Additional Images
- 22 External Links
- 23 Glossary Links
Fertilization is the fusion of haploid gametes, egg and sperm, to form the diploid zygote. Note though there can be subtle differences in the fertilization process which occurs naturally within the body or through reproductive technologies outside the body, the overall product in both cases is a diplod zygote. In fertilization research, after humans the mouse is the most studied species followed by domestic and farm animals. The process of fertilization involves components of, and signaling between, both sperm (spermatozoa) and egg (oocyte).
In addition to in vivo fertilization there are many new in vitro technologies related to human infertility (Assisted Reproductive Technology) and animal production somatic cell nuclear transfer (SCNT) to generate a zygote.
Note different spelling - USA spelling "Fertilization", Australian spelling "Fertilisation".
- Fertilization Links: Fertilization | Oocyte | Spermatozoa | Cell Division - Meiosis | Zona pellucida | Zygote | Lecture - Fertilization | Cell Division - Mitosis | Lecture - Week 1 and 2 | Hydatidiform Mole | Assisted Reproductive Technology | Lecture - Genital Development| Menstrual Cycle | Morula | Blastocyst
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Bas Brinkhof, Helena T A van Tol, Marian J A Groot Koerkamp, Richard W Wubbolts, Henk P Haagsman, Bernard A J Roelen Characterization of bovine embryos cultured under conditions appropriate for sustaining human naïve pluripotency. PLoS ONE: 2017, 12(2);e0172920 PubMed 28241084
Alex Harkness Digest: Prudent self-denial: the advantage of incompatibility in Leavenworthia alabamica. Evolution: 2017; PubMed 28240770
Budi Wiweko, Pramety Utami Predictive value of sperm deoxyribonucleic acid (DNA) fragmentation index in male infertility. Basic Clin Androl: 2017, 27;1 PubMed 28239474
Carlos Zumoffen, Matías D Gómez-Elías, Adriana M Caille, Luis Bahamondes, Patricia S Cuasnicú, Débora J Cohen, María José Munuce Study of the effect of ulipristal acetate on human sperm ability to interact with tubal tissue and cumulus-oocyte-complexes. Contraception: 2017; PubMed 28238840
Qian Zhang, Guangyu Li, Lei Zhang, Xiaohe Sun, Dandan Zhang, Juanjuan Lu, Jinlong Ma, Junhao Yan, Zi-Jiang Chen Maternal common variant rs2305957 spanning PLK4 is associated with blastocyst formation and early recurrent miscarriage. Fertil. Steril.: 2017; PubMed 28238495
- Understand the mechanisms of gamete formation.
- Understand the mechanisms of cell division.
- Describe the differences between mitosis and meiosis.
- Understand the mechanisms of fertilization, both in vivo and in vitro.
- Describe the cleavage of the zygote.
- Have a preliminary understanding of the role and process in male sex determination and X inactivation.
- Understand the abnormalities that occur during this period of 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 24-72h 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, ZP4 (mouse only ZP1-3)
- mechanical protection of egg
- 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
- 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)
- Links: Spermatozoa Development
- Human Ejaculate
- 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.
- Ovulation-inducing factor identified in several species.
Marcelo H Ratto, Yvonne A Leduc, Ximena P Valderrama, Karin E van Straaten, Louis T J Delbaere, Roger A Pierson, Gregg P Adams The nerve of ovulation-inducing factor in semen. Proc. Natl. Acad. Sci. U.S.A.: 2012, 109(37);15042-7 PubMed 22908303
- 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
Clinical guidelines have typically identified the "fertile window" between days 10 and 17 within the typical 28 day menstrual cycle.
- fertile window occurred during a broad range of days in the menstrual cycle.
- between days 6 and 21 women had at minimum a 10% probability of being in their fertile window.
- women cannot predict a sporadic late ovulation; 4 - 6% of women whose cycles had not yet resumed were potentially fertile in the fifth week of their cycle.
- only about 30% of women is the fertile window entirely within the days of the menstrual cycle identified by clinical guidelines (between days 10 and 17)
- most women reach their fertile window earlier and others much later.
- women should be advised that the timing of their fertile window can be highly unpredictable, even if their cycles are usually regular.
- 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 ZP2 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
- Contact between spermatozoa and oocyte egg coat (zona pellucida [ZP]) glycoproteins triggers increases in intracellular calcium ion (iCa2+) concentration in spermatozoa
- CATSPER channels on the distal portion of sperm (the principal piece) are required for the ZP-induced iCa2+ increases
- iCa2+ increase starts from the spermatozoa tail and propagates toward the head
- Store depletion-activated Ca2+ entry is thought to mediate the sustained phase
Fertilization - Oocyte
- Membrane Depolarization - in non-mammalian species, caused by sperm membrane fusion, acts as a 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 ZP2 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)
Spermatozoa - Oocyte Interaction
Spermatozoa and oocyte fusion in the membrane adhesion area requires the presence of 3 membrane proteins (spermatozoa Izumo1; oocyte receptor Juno and Cd9).
The sperm-specific protein Izumo is named for a Japanese shrine dedicated to marriage and is essential for sperm-egg plasma membrane binding and fusion. It interacts with the spermatozoa folate receptor 4 (Folr4).
- Links: OMIM 609278
folate receptor 4 (Folr4)
Folate receptors are also known as the folic acid (FA) binding protein and bind of 5-methyltetrahydrofolate (5-MeTHF).
Oocyte cell surface protein acts as a receptor for pregnancy-specific glycoprotein 17 (Psg17).
- Links: OMIM 143030
|(Astacin-Like Metalloendopeptidase, ASTL) An oocyte enzyme (zinc-dependent metalloprotease) involved in altering zona pellucida structure, by cleaving zona pellucida glycoprotein (ZP2), following fertilisation. This change in zona pellucida structure is one of the blockers to polyspermy.|
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
- Spermatozoa contributes - centriole which organizes mitotic spindle
- Oocyte contributes - mitochondria (maternally inherited)
- Mitochondria of the spermatozoa are specifically destroyed in early development by proteolysis (mouse 4 to 8 cell transition).
- Metaphase II oocytes in rats have an average mitochondrial DNA (mtDNA) copy number of 147,600 (+/-3000) that only increases at the 8-cell stage.
- 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.
Fertilization Protein Changes
A recent study in mice has shown that after fertilization the maternal proteins present in the original oocyte are quickly degraded by the zygote stage. MII oocytes have 185,643 different peptides while zygotes contain only 85,369 peptides.
Protein Expression Classified by Molecular Functions
The abnormalities listed below relate to genetic abnormalities occurring during fertilisation. There are of course many additional genetic abnormalities inherited and introduced by the recombined maternal and paternal genomes, other than trisomy 21 these will not be covered here.
Complete Hydatidiform Mole
- Chromosomal genetic material from the oocyte (ovum, egg) is lost, by an unknown process.
- Fertilization then occurs with one or two spermatozoa and an androgenic (from the male only) conceptus (fertilized oocyte) is formed.
- The embryo (fetus, baby) does not develop at all but the placenta does grow.
Partial Hydatidiform Mole
Three sets of chromosomes instead of the usual two and this is called triploidy.
- chromosomal (genetic) material from the oocyte (ovum, egg) is retained and the egg is fertilized by one or two spermatozoa.
- with partial mole there are maternal chromosomes and there is a fetus.
- the three sets of chromosomes means the fetus is always grossly abnormal and will not survive.
(Greek, parthenos = virgin, genesis = birth) The development of an unfertilized oocyte (no spermatozoa). Other than mammals, many different species (plants, insects, reptiles) can develop from unfertilized eggs. An embryo so formed without sperm contribution. Blocking of parthenogenesis in mammals appears to be related to genomic imprinting. Abnormal parthenogenic processes can occur in mammals, and more recently a parthenogenic mouse has been made in the laboratory.
Trisomy 21 (Down's or Down syndrome) is caused by nondisjunction of chromosome 21 in a parent who is chromosomally normal and is one of the most common chromosomal aneuploidy abnormalities in liveborn children. The frequency of trisomy 21 in the population is approximately 1 in 650 to 1,000 live births, in Australia between 1991-97 there were 2,358 Trisomy 21 infants. There are other less frequently occurring trisomies (18, 13 and X).
- Links: Trisomy 21
- Diego Rafael Uñates, Héctor Alejandro Guidobaldi, Laura Virginia Gatica, Marisa Angélica Cubilla, María Eugenia Teves, Ayelén Moreno, Laura Cecilia Giojalas Versatile action of picomolar gradients of progesterone on different sperm subpopulations. PLoS ONE: 2014, 9(3);e91181 PubMed 24614230
- Yasuhiro Yamauchi, Jeffrey A Shaman, W Steven Ward Non-genetic contributions of the sperm nucleus to embryonic development. Asian J. Androl.: 2011, 13(1);31-5 PubMed 20953203
- Antoine Jégou, Ahmed Ziyyat, Virginie Barraud-Lange, Eric Perez, Jean Philippe Wolf, Frédéric Pincet, Christine Gourier CD9 tetraspanin generates fusion competent sites on the egg membrane for mammalian fertilization. Proc. Natl. Acad. Sci. U.S.A.: 2011, 108(27);10946-51 PubMed 21690351
- Gagandeep Gahlay, Lyn Gauthier, Boris Baibakov, Olga Epifano, Jurrien Dean Gamete recognition in mice depends on the cleavage status of an egg's zona pellucida protein. Science: 2010, 329(5988);216-9 PubMed 20616279
- Paul M Wassarman Zona pellucida glycoproteins. J. Biol. Chem.: 2008, 283(36);24285-9 PubMed 18539589 | J Biol Chem.
- Hong-Xia Zhou, Yu-Zhen Ma, Ying-Lei Liu, Ying Chen, Cheng-Jie Zhou, Sha-Na Wu, Jiang-Peng Shen, Cheng-Guang Liang Assessment of mouse germinal vesicle stage oocyte quality by evaluating the cumulus layer, zona pellucida, and perivitelline space. PLoS ONE: 2014, 9(8);e105812 PubMed 25144310 | PLoS One.
- A J Wilcox, D Dunson, D D Baird The timing of the "fertile window" in the menstrual cycle: day specific estimates from a prospective study. BMJ: 2000, 321(7271);1259-62 PubMed 11082086 | PMC27529 | BMJ
- Jingsheng Xia, Dejian Ren Egg coat proteins activate calcium entry into mouse sperm via CATSPER channels. Biol. Reprod.: 2009, 80(6);1092-8 PubMed 19211808
- Myriam Chalbi, Virginie Barraud-Lange, Benjamin Ravaux, Kevin Howan, Nicolas Rodriguez, Pierre Soule, Arnaud Ndzoudi, Claude Boucheix, Eric Rubinstein, Jean Philippe Wolf, Ahmed Ziyyat, Eric Perez, Frédéric Pincet, Christine Gourier Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9 accumulation in the intercellular contact area prior to fusion during mammalian fertilization. Development: 2014, 141(19);3732-9 PubMed 25209248
- Anna D Burkart, Bo Xiong, Boris Baibakov, Maria Jiménez-Movilla, Jurrien Dean Ovastacin, a cortical granule protease, cleaves ZP2 in the zona pellucida to prevent polyspermy. J. Cell Biol.: 2012, 197(1);37-44 PubMed 22472438
- J M Cummins Fertilization and elimination of the paternal mitochondrial genome. Hum. Reprod.: 2000, 15 Suppl 2;92-101 PubMed 11041517
- Yuichi Kameyama, France Filion, Jae Gyu Yoo, Lawrence C Smith Characterization of mitochondrial replication and transcription control during rat early development in vivo and in vitro. Reproduction: 2007, 133(2);423-32 PubMed 17307910
- Shufang Wang, Zhaohui Kou, Zhiyi Jing, Yu Zhang, Xinzheng Guo, Mengqiu Dong, Ian Wilmut, Shaorong Gao Proteome of mouse oocytes at different developmental stages. Proc. Natl. Acad. Sci. U.S.A.: 2010, 107(41);17639-44 PubMed 20876089 | PNAS
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- fertilization - All (51803) Review (5928) Free Full Text (11715)
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- PBS - First Human Eggs Fertilized in a Laboratory 1944.
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Cite this page: Hill, M.A. 2017 Embryology Fertilization. Retrieved February 28, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Fertilization
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