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Tuesday April 6, 2010 How to Convert an egg in sperm? Bibliographic analysis of the epigenetic GAMETES
Blgo. Luis Arbaiza
biologist with a major in genetics Universidad Nacional Mayor de San Marcos.
1 .- INTRODUCTION
A sperm and an egg are genetically identical, which would, theoretically, use of assisted reproduction techniques (especially ICSI, intracytoplasmic injection) for attaining the fertility and biological paternity gametes of the same type (two eggs or two sperm)
But despite their genetic equality, egg and sperm are different epi-genetically.
This epigenetic difference of gametes is called imprinting. Having a maternal and a paternal imprinting.
The union of two gametes, one with other maternal and paternal imprinting allows normal development of the embryo.
The union of gametes with the same imprinting leads to different epigenetic defects and embryonic development unviable. Convert
paternal imprinting in maternal sperm in vitro may permit conversion, epigenetically speaking, a sperm egg, which is perfectly possible biological paternity from the genetic material.
But it is this difference that causes epigenetic? Even
can not completely answer this question.
The motivation of this research is to discover literature.
2 .- WHAT IS THE IMPRINTING?
A gene can be turned on or off. There are a number of
genes that are turned on and off the sperm into eggs. These genes are involved in imprinting.
Thus, eggs and sperm have the same genes but they are active in them. And this makes them functionally different.
The on or off which gives rise to male or female imprinting is a specific and consistent pattern that occurs in gametogenesis.
many and which genes are involved in the imprinting is something that is known only partially. JUSTIFICATION
1 .- The genetic imprint is required for normal development of embryos
This is done in the germ line
The error must carry errors that prevent the successful development of embryos.
Especially in those procedures like ICSI epignéticos processes that accelerate the male gamete.
has been shown greater percentage of epigenetic disease patient
ICSI children have been encontradon defects in the methylation of H19 and MEST IN OLIGOZOSPERMICOS (CJ Marques 2008) This may explain the appearance of the Silver-Russell syndrome in children born with H19 hypomethylation ART. (CJ Marques 2008) also
low unmethylation of the CTCF-binding site Could lead to inactivation of the paternal IGF2 gene, and Be Linked to Decreased embryo quality and birth weight, Often associated with ART. (CJ Marques 2008)
2 .- Imrpinting is a limit to cloning because there is no time for proper reprogramming new drugs
3 .- 4 .- engineering epigenetics
3 .- delimitation of the problem
We have brought several questions even without a complete response: 3.1
Which genes are they?
3.2 When you change?
3.3 Who the changes? 3.4
how the changes?
3.5 What is the uncaused cause of imprinting? Is it genetic or epigenetic?
3.6 What is the relationship with the Sry gene which is obviously the only difference between male genome and feminine and oh to be the starting point of this differentiation? MATERIALS AND METHODS
literature was analyzed in subjects related to try to answer the research questions
For what is agreed to virtual libraries
And software data management. RESULTS
BIBLIOGRAPHIC ANALYSIS QUESTIONS
3.1 WHAT ARE THE GENES? GENES INVOLVED IN IMPRINTING
genome imprinting There are about 156 possible new genes, and imprinting status-gene can be predicted by its sequence (Luedi, PP et al. (2007). The classic mechanism of genetic imprinting of a gene is methylation but not the only and does not necessarily mean inactivation.
Here is a list of some genes known as imprinting involved in the human. Chromosome location
GEN
State sperm into the egg activator State
1 NOEY2
function active (tumor suppressor)
active IGF2 Independent control of others, the change carries many more
7p12 genes (GRB10) in growth factor receptor protein 10
7 q21 PEG10 active inactivated may be a new gene imprinting
7q31.3 MEST isoforms 1 and 2, 8 KCNK9
(active in the brain causes cancer, bipolar and epilepcia)
DLGAP2 8p23 (possible Bladder tumor suppressor)
DLGAP2
associated protein-2 (Dlgap2). WAS
Excluded as the gene responsible for EPMR.
11
inactive H19 noncoding RNA active role in cancer
a member of the AP2 transcription factor family transcription factor E2F1
uan
may control differently from the other
His other genes change more
drag
11 p57, CDKN1C Kip2 active
MEG3
14 q, 15 q11-q13
active SNRPN (small nuclear ribonucleoprotein, polypeptide N) 15 q11-q13
IPW functions not
polypeptide RNA. Predominantly in brain
15 Causes UBE3A Angelman syndrome. on the mother's chromosome Possible 19q13.4
master key active XIST
inactive X
Idica that methylation is removed in spermatogenesis Xist (is in mice)
NESP55
ATP10A
PHLDA2
NDN
MAGEL2
inactive SNRPN
PEG3
KCNQ1OT1
KCNQ1 TP73
CDKN1C
IGF2R
WT1
SLC22A18
3.2 What HAPPENS WHEN IMPRINTING?
During the development of primordial germ cells the pattern of imprinting is erased. Likely to enter the gonad.
in spermatogenesis is completed in the haploid phase (meiosis) in man meiosis occurs before the father as soon as when spermatogonia proliferate, according to some authors is intrinsic and cell-Autonomous.
oogenesis in the imprinting occurs in ocytes and around the time of the first meiotic division, the methylation in women occurs in postnatal development when ooccitos are diplotene prophase I, the maternal imprinting continuously established in the maturation of oocytes .
But methylation may be at different times for different genes (Paolini 2004)
has been found not to be due to the influence of somatic cells of the genital ridge or gonad environment in primary cells. (Paolini 2004) SPERMATOGENESIS
Time
STAGE TIME OF IMPRINTING PHOTO ESATDO
0 Zygote is exaggerated DIFERENCAI
imprinting paternal methylation demethylated shortly after fertilization, and the mother suffers
novo methylation of 4 hours
pronucleus in mouse father is demethylated within 4 hours after fertilization
4 hours
A global demethylation occurs in the morula at 4 h of fertilization. 5 days
reestablished in the blastocyst inner cell methylation in mass but not in the trophectoderm. In the blastocyst reestablesce methylation in the inner cell mass but not in the trophectoderm. (Kierszenbaum AL. 2002)
Primordial germ cells 3-4 weeks as PGCs have migrated paternal and maternal imprinting The Primordial germ cells inherit a biallelic imprinting father and mother, and delete your imprinting to start a de novo during gametogenesis. (Kierszenbaum AL. 2002)
primordial germ cells expressing these genes: Blimp1, Oct3 / 4, Fragilis, Stella, c-Kit, MVH, DAZL and Gcna1 (Deshira Saiti 2000)
H19 and Igf2 are expressed in endoderm and mesoderm (Andrea L. Webber January 1998)
6 weeks Embrionic
germ cells have no imprinting or is deregulated, and gonad are primordial cells
40 are intended to be induced gonad Exra-embryonic tissues that are hypothesized to repress cell
Blimp1 somatization program (or Prdm1), a repressor that foundation helps tarscripcion (Yasuhide Ohinata 2005)
at birth and in some months parental imprinting is completed puberty Start esperamatogenesis
. The paternalisacion is an ongoing process in-Dividing mitotically and meiotically spermatogonial stem cell-derived progeny Dividing spermatocyte (Kierszenbaum AL. 2002)
Dnmt3L and Dnmt3b interact with Dnmt2a and Dnmt3b and is required for proper spermatogenesis. (Kierszenbaum AL. 2002)
The imprinting is already mature in the stem cell line in germinal (CJ Marques 2008)
Spermatogonia are immature germ cells do mitosis
Some differ to primary spermatocytes.
After the first meiosis spermatocytes become secondary
2
These are meiosis 2 and form 2 spermatids
Spermatogonia (diploid) are in speramtozoides already methylated H19
THE AMENDING 3.4 Who?
to imprint genes are usually methylated in its promoter (methylation is the addition of a methyl group on a Carbon nucleotide)
promoters are rich in CpG islands
5-methylcytosine occurs at reacting DNA methyltransferases (DNMT 1, 3a or 3b), which catalyzes the transfer of a methyl group (CH3) from S-adenosylmethionine (SAM) carbon 5 of cytosine methylated
These islands are susceptible to bind to proteins (eg MECP2 "methyl CpG-binding protein 2)
Dnmt3a and Dnmt3b are de novo methylation Dnmt1
when divided by a new DNA methylation in the daughter strand
The demethylation occurs in the absence of Dnmt1 with rounds of DNA replication Continued (passive demethylation), as Actively as well (without DNA replication). The nature of demethyl is unknown.
Dnmt3L assists de novo methylation
Between 60 and 90% of methylated CpG (rare those imprintin few)
Methylation make DNMT1, DNMT3A, DNMT3B Dnmt3a and Dnmt3b appear to be the giving patterns of methylation in the early embryo
DNMT1 is what keeps this pattern of mother cell to daughter (two copies)
methylation is not always
silencing is methylation changes chromatin structure
A pattern of methylation is the result of: 1 .-
de novo methylation maintenance
2 .- 3 .- demethylation
(Paolini 2004)
generally expressed genes in the imprinting raise parental fetal development while it limits the maternal.
(Paolini 2004)
MASH2 regulates the development of spongiotrophoblast
Igf2 has been found in ASCL2
labyrinthine trophoblast is expressed in spongiotrophoblast and labyrinthine
3.5 What is the uncaused cause imprinting?
KCNQ1OT1 The expression of the gene on chromosome 11p15.5, is essential for the imprinting of certain regions. The mechanism may be a gene is active in a ovarian or spermatic say this cascade occurs in other imprinting genes.
studying their transcricion factors could be achieved by knowing what the root causes of IGF2 imprinting
19q13.4
H19 IGF2 H19
19q13.4
The ergenic germline-derived differentially methylated region (IG-DMR) ES CANDIDATOPARA REGION CONTROL OF CHROMOSOME 12
is a cluster that contains: Paternally
Expressed protein-coding genes Dlk1 and DIO3 and several non-coding RNAs, including maternal expression of Gtl2 and C / D snoRNAs.
A retrotransposon-like gene (Rtl1) is Expressed from the paternal chromosome and has an antisense transcript from the maternal Expressed chromosome containing two microRNAs with full Complementarity to Rtl1
Deletion of IG-DMR of the maternal chromosome causes loss of imprinting in all cluster genes
The deletion leaves intact the parental imprinting
Some women do not have a piece of chromosome, 19q13.4 and its imprinting pattern in their eggs is paternal
EXPERIMENT 2 MOTHERS
The zygote genome did so with mature and an immature (Tomohiro Kono 2004) The oocyte was not developed a mouse mutant with a deletion of 13-kilobase
The maternal methylation occurs on oocyte maturation is
The undeveloped (ng)
and development (fg)
But in the ng was not altered Igf2 H19 and H19
To block ng was used in a mouse with a deletion in the gene
The embryos were born to 17.5 days
was confirmed that these embryos do not spend the day 17.5
The 2 were born with retarded growth an underdeveloped liver Igf2 and H19
As Dlk1 and Gtl2 are printed on spermatogenesis. Modification
IMPRINTING synthetic estrogen, diethylstilbestrol (DES) dog developmentally imprint genes by Changing the pattern of DNA methylation. (John A. McLachlan, 2001)
The exreecion of imprinted genes and fetal development is influenced by the addition of fetal calf serum culture medium (Paolini 2004)
not known how this environment affects imprinting Maybe
removes methyl groups, leading to incomplete or clear the pattern of imprinting. (Paolini 2004)
E IMPRINTING
ICSI ICSI Children weigh less (Paolini 2004)
EXPERIMENT
First female sperm stem cells turned into sperm that impregnated
(Nayernia K 2006)
marrow cells were transformed into cells There was an expression of male germ stem cells markers (Nayernia K. 2007)
born mouse had defects and will use special chemicals and vitamins
PRODUCER OF SPERM WOMAN
A molas locus 19q13.4. Examined the methylation in the daughters and the mola
They used the two bisulfite-based Methods (¿??)
The mutation is inherited from the grandfather or maternal grandfather so we conclude that the error was not deleted due to the imprinting marks if not quite the re-establishment of native brands in oogenesis or in post-cigotic maintenance (El-O Maarri 2003)
DISCUSSION
There are apparently two mechanisms that depend locomotive the imprinting of these mechanisms must be related to the presence or absence of SRY but that relationship is still nebulous.
is known that some methylating enzyme is responsible for imprinting genes, these genes also are rich in CpG islands but because in a gamete are methylated and not in another, still the same question arises how this enzyme known to methylate genes and which are not? And as you know when methylated if a sperm or an egg. Some of these enzymes also signal a different or activates these enzymes
The mechanism may be a gene is active in a ovarian or spermatic say this cascade occurs in other imprinting genes. Another question
that emerges from this analysis is Are there polymorphisms in the imprinting genes?)
abortions should study what ICSI and art to see how they are epigenetically by altering these techniques the normal maturation of imprinting in the gametes. There is already evidence of increased disease epigenetic ARTs cup
Deletion of IG-DMR of the maternal chromosome causes loss of imprinting on all cluster genes that marks it as a locomotive gene imprinting.
The deletion leaves intact the parental imprinting
Some women do not have a piece of chromosome: 19q13.4
This healthy gene feminizaría eggs.
sperm could feminize H19 and Igf2, apparently, are printed by a mechanism independent of this.
Achieving the correct expression of IGF2 and ha19 a large number of other genes is well placed (maternal bone becomes father)
The experiment of mice with two mothers can deduce the following: "You can
concluded that an immature oocyte and sperm except for 2 genes (IGF2 and H19)
-one was nullified (h19) to get the sperm
-hence a sperm and an egg is immature except for 2 genes
- If you add the egg maturation factors and vanishes IGF2 could turn sperm into eggs.
weigh less ivf Apparently, that talks about winning the maternal genes that bone paternal genes are incomplete
WOMEN PRODUCERS MDE SPERM
If there is a mutation that makes the maternal genome paternal
1 .- A simple element determines parenthood
genome that gene 2.-feminizaría healthy sperm. 3 .- partenisación
genome requires no activation or suppression of this gene or factor.
The normal state is paternal
may first have to delete and then print
We hypothesize that the factor of follicular development as well as IGF2 gene silencing can change the parental imprinting of the sperm mother
CONCLUSION Two mechanisms start the cascade of events leading to the pattern of paternal or maternal imprinting.
A gene in 19q13.4 is responsible for feminizaría a significant number of genes to print
And another alter H19 and Igf2
Thanks
BIBLIOGRAPHY
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