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www.rbmonline.com/Article/2141 on web 7 March 2006

Article
Paternal and maternal factors in
preimplantation embryogenesis: interaction
with the biochemical environment
After beginning his career with INRA, Dr Ménézo became head of the assisted reproductive
technology department at Laboratoire Marcel Mérieux in 1990. He owns several patents,
best known is probably for the INRA B2 Ménézo Medium. His awards include the 2001 Gold
Medal of the Department of Obstetrics and Gynecology of the Institiut Dexeus, Barcelona.
He has over 250 international scientific publications and book chapters to his name and has
been active on many courses over the years. He reviews for many international journals and
is on the editorial board of Genesis, Referenes En Gynecology Ey Ostetrique and Zygote.
Dr Ménézo has served on many organizing committees and is a member of several learned
societies. He is currently a member of the France–USSR commission for the study of
Fertility. He is married with three children.

Dr Yves JR Ménézo
Yves JR Ménézo
Institut Rhonalpin, Centre de FIV de la clinique du Val d’Ouest
Chemin de la Vernique, 69130 Ecully, France
Correspondence: e-mail : yves.menezo@club-internet.fr

Abstract
Paternal effect on embryonic development occurs as early as fertilization. Incorrect formation of the spermatozoon due to
centrosome defects and abnormal concentrations of any components involved in the activation process lead to failure immediately
or in the subsequent cell cycles. Sperm chromosomal abnormalities result in early embryo developmental arrests. Generally
poor spermatozoa lead to poor blastocyst formation. Sperm DNA fragmentation may impair even late post-implantation
development. The DNA repair capacity of the oocytes is of major importance. Early preimplantation development, i.e. until
maternal to zygotic transition, is maternally driven. Maternal mRNAs and proteins are of major importance, as there is an
unavoidable turnover of these reserves. Polyadenylation of these mRNAs is precisely controlled, in order to avoid too early or
too late transcription and translation of the housekeeping genes. An important set of maternal regulations, such as DNA stability,
transcriptional regulation and protection against oxidative stress, are impaired by age. The embryo biochemical endogenous
pool is very important and may depend upon the environment, i.e. the culture medium. Paternal, maternal and environmental
factors are unavoidable parameters; they become evident when age impairs oocyte quality.

Keywords: apoptosis, glucose, imprinting, methionine, oocyte, sperm

in fertility is not simply related to sperm penetration failure.

Introduction
During the early time of IVF, male fertility was defined as the
possibility of spermatozoa to fertilize the oocyte, and to obtain
early cleavage stage embryos. In human IVF, the obtainment
of 2- to 4-cell embryos was considered as a test for sperm
fertilizing ability. It was assumed that all the embryos obtained
had the same developmental potential, whatever the quality of
spermatozoa and oocytes. Subsequently, several authors (Ron-
El et al., 1991) observed that poor morphological quality and
poor developmental ability were associated with severe sperm
morphology defects and oligoasthenospermia. In humans,
the same negative relationship was observed between sperm
quality and the ability to achieve the blastocyst stage (Janny
616 and Ménézo, 1994). It is now acknowledged that difference
Oocyte quality is also of major importance: it fully controls
the first divisions until genomic activation. This aspect leads
directly to the quality of the female gamete. In young oocytes,
sperm decays can be repaired and pregnancy can continue to
term. In older patients, unrepaired sperm DNA leads to earlier
or later abortion (Hamatani et al., 2004). Maternal age is one
of the most important negative factors in human reproduction:
it impairs chromosome segregation. Aneuploidy and
polyploidy are critically related to age: this leads to unbalanced
chromosome complement. Trisomies 13 and 21 are the most
frequent in the embryos of older mothers. Age-related impaired
quality of cytoplasmic maturation interferes, as it involves
DNA and chromosome stability (Hamatani et al., 2004). The
endogenous pool of metabolites will allow proper synthesis
of the proteins required for housekeeping and intermediate

metabolic activity; this involves correct concentrations of the
metabolite transporters. Genomic activation at the proper time
is mandatory. Turnover of the mRNAs is a natural process
which starts even before fertilization. Maternal mRNAs are
stored during maturation and the fine regulation through
polyadenylation occurs during the very final stages. This has
two major effects: (i) allowing translation with an accurate
timing, and (ii) preventing a too rapid degradation of the
important mRNA. It has been demonstrated that most of the
enzymes involved in prevention of free radical decays are
submitted to elongation of polyA tails in human oocytes, but
not in mouse oocytes.
The ‘free floating’ embryo has also to manage in vitro with the
culture medium. It has to be equilibrated and must fulfil the
requirements. This study will show some aspects of positive
and negative embryo culture medium interactions.
Paternal effect
Early defects at fertilization and
immediately after
The centrosome
The first epigenetic contribution of the spermatozoon is the
centrosome, the microtubule-organizing centre of the cell.
Correct assembly and function of microtubules is fundamental
for the separation of chromosomes at meiosis and migration of
the male and female pronuclei. The maternal inheritance observed
in mice caused confusion until the work of Schatten (1994) and
Simerly et al. (1995). Considering the semi-conservative form
of this organelle and its critical role in mitosis, it seems obvious
that a functionally imperfect centrosome borne by a subnormal
spermatozoon induces problems in early embryogenesis, i.e.
formation of cytoplasmic fragments and abnormal distribution of
the chromosomes (Palermo et al., 1994; Simerly et al., 1995).
Up to 25% of the non-dividing eggs are in fact fertilized but
submitted to cell division defects (Renard et al., 1994). Centrin
and gamma-tubulin could be involved in this pathology of the
centrosome.
Oocyte activation factors
It is generally agreed that intracellular Ca2+ is the universal signal
for triggering oocytes into metabolic activity. A heat-sensitive
(Dozortsev et al., 1995) and soluble protein, a phospholipase
zeta and not oscillin (Swann et al., 2004), induces activation
through calcium oscillations. Defects in soluble activating
factors could account for delays in zygote formation (Ron El et
al., 1991), but poor chromatin packaging contributes to failure
of sperm decondensation, independently of any activation
problems (Sakkas et al., 1996).
One-third of human IVF embryos fail, in vitro, around the
time of genomic activation (Janny and Ménézo, 1994). It is
quite surprising to expect a paternally derived influence before
genomic activation: this means before the appearance of the
first products resulting from the first massive transcriptions
involving the paternal genome. A rather small transcriptional
activity, involving only the sexual chromosome, is observed as
Article - Preimplantation embryo development - YJR Ménézo
early as PN formation (Ao et al., 1994). There is obviously a
race against clock between, on the one hand, the turnover of
the maternal messenger mRNA and, on the other hand, the
first massive synthesis of embryonic transcripts. Suboptimal
spermatozoa surely lead to developmental delays, as the
fertilization process is already delayed (Janny et al., 1994):
it can be assumed that the maternal mRNA reaches a critical
threshold, impairing proper genomic activation.
Developmental arrests between genomic
activation and implantation
After genomic activation, the transition between morula
and blastocyst is very sensitive. A complex remodelling in
the embryo occurs with the first differentiations. In work on
human IVF blastocysts (Janny et al., 1994), an embryo loss was
observed at this point: the loss was significantly increased in the
poor quality sperm group (31 versus 22% for control group).
The altered spermatozoon obviously has a negative role on
preimplantation development, even after genomic activation,
One of the most exciting models concerning a severe paternal
effect is linked to genetic aspects. In the DDK strain, the first
paternal products of transcription and translation can have very
deleterious interactions with the maternal cytoplasm, leading
to complete necrosis and cytolysis just prior to blastocyst
formation (Renard et al., 1994).
Intracytoplasmic sperm injection
Intracytoplasmic sperm injection (ICSI) is one of the most
interesting breakthroughs in the treatment of male infertility.
In human IVF with poor quality spermatozoa, the cumulative
effect of the delay in fertilization (Ron El et al., 1991) and
the delays associated with the epigenetic problems may cause
prolonged cell cycles and late divisions (2-cell embryos on day
2, 4-cell on day 3). This leads to developmental arrests around
genomic activation, in relation to the depletion of (some of) the
maternal mRNA. ICSI saves time, at least for the fertilization
process, since spermatozoa are introduced into the cytoplasm.
Recent observations (Morozumi and Yanagimachi, 2005)
have highlighted the possible negative effect of acrosome
injection. ICSI spermatozoa do not show typical interactions
with the oocytes (Hewitson et al., 2000; Takeuchi et al., 2004).
Acrosomal enzymes (trypsin-like and hyaluronidase) normally
eliminated before sperm entry may have deleterious effects on
cytoplasm. The second aspect is the delayed swelling of the
chromatin close to the acrosome. The non-random positioning
of the chromosome in the sperm head (Hazzouri et al., 2000)
probably leads to the increased anomalies observed for the
gonosomes. The data (Janny and Ménézo 1994) show that
blastocyst formation is similar for ICSI and IVF for the overall
population. However, more ICSI couples produce embryos
unable to reach the blastocyst stage. It seems to be an ‘all or
nothing’ rule: when patients have blastocysts, they are obtained
with good yield, but more couples fail to obtain at least one
blastocyst. The ICSI process carries other problems: oligo-
asthenoteratozoospermia may be linked to genetic disorders.
Whether or not the negative influence of suboptimal spermatozoa
is linked to the integrity and quality of the paternal DNA is no
longer a matter for conjecture. An increase in chromosomal
abnormalities is consistently described as a function of sperm
count (Bourouillou et al., 1985) and for non-obstructive 617
 Article - Preimplantation embryo development - YJR Ménézo
azoospermia versus obstructive azoospermia.
Maternal factors
Early preimplantation development, i.e. until maternal to
zygotic transition (MZT), is under maternal control. Maternal
mRNA and protein content of the oocytes, stored during oocyte
growth and maturation, is of major importance, as there is an
unavoidable turnover of these reserves, even before ovulation.
Decreasing oocyte competence with age is one of the major
causes of (human) infertility.
Maternal age impairs chromosome segregation. Aneuploidy
and polyploidy are increased with age: this leads to unbalanced
chromosome complement. The most well known trisomies
observed in embryos of older women are 13 and 21. The
DNA repair capacity of the oocytes has also to be considered.
In oocytes from young women, sperm decays can be
repaired and pregnancy can proceed to term. Lack of repair
of chemically modified (oxidized) bases in DNA may have
severe consequences: un-repaired DNA leads to compounded
damage and errant transcripts, sources of cell death and/or
mutagenesis leading to cancer (Boiteux and Radicella, 2000).
Whatever the quality of spermatozoa, there is an unavoidable
level of DNA fragmentation: even for the best spermatozoa, a
5% fragmentation level is observed (Guerin et al., 2005). DNA
decays must be repaired before and during the PN stage. The
extremities of the chromosomes are protected by the telomeres:
they prevent, at least in part, the chromosomes from being
submitted to improper DNA repair. If telomeres are reduced in
length, a DNA repair response is activated, with activation of
p53 (tumour suppressor). p53 has a critical role: a decrease in
its activity will allow fusion between chromosomes, formation
of chromosome bridges and DNA breaks leading chromosome
abnormality and to cancer. Recent observations have clearly
associated sperm DNA fragmentation and shortening of the
telomeres (Rodriguez et al., 2005).
However, age-related impaired quality of cytoplasm
maturation is also dramatically important. Three parameters
are influenced by maternal age: quality of the endogenous
metabolite pool (especially amino acids), alteration of gene
expression patterns, and regulation of mRNA polyadenylation.
Five percent of the 11,000 genes whose transcripts are detected
in oocytes show statistically significant expression decrease
(Hamatani et al., 2004). It is not a global decline, but some
important genes involved in metabolic control, such as those
contributing to oxidative stress prevention and mitochondrial
function, are negatively affected. This is also true for DNA
methylation, genome stability and chromatin structure
(Hamatani et al., 2004). With other epigenetic processes,
polyadenylation of mRNA is precisely controlled, in order to
avoid too early or too late translation of the genes involved
in intermediate metabolism and housekeeping. Three major
elements are involved in the proper polyadenylation of mRNA
and adequate translation with correct timing. CPE (cytoplasmic
polyadenylation element binding protein) and ePAB (polyA
binding protein; Seli et al. 2005) will allow or not (i.e. storage)
translation of the mRNAs, the polyadenylation of which has
been controlled by polyadenylate polymerase (PAP). The
endogenous pool of metabolites will allow proper synthesis of
the proteins required for the embryonic metabolic machinery;
618
it also requires the correct level of the metabolite transporters.
This will allow genomic activation to be achieved at the
proper time. Turnover of the mRNA is a natural process which
starts even before fertilization. Maternal mRNAs are stored
during maturation and fine regulation through polyadenylation
occurs during the very final stages. It was found that growth
hormone plays a direct role in this regulation in the naked
oocytes, and not through the cumulus cells (El Mouatassim
et al., 1999). Polyadenylation has two major effects: (i)
allowing translation with accurate timing, and (ii) preventing
a too-rapid degradation of the important mRNA. It has been
demonstrated that most of the enzymes involved in prevention
of free radical decay are submitted to elongation of polyA tails
in human oocytes but not in mouse oocytes (El Mouatassim
et al., 1999). This is also the case for the chaperone protein
basigin (Herubel et al., 2002).
In fact, it is sometimes very difficult to distinguish between
maternal and metabolic factors, as they are so tightly joined.
For example, insufficient storage of monocarboxylate
transporters regulating intracellular pH and/or maintaining the
NAD+/NADH ratio will affect internal homeostasis and pH,
thus affect developmental programming (Dale et al., 1998):
early preimplantation embryos are not able to cope with acidic
conditions.
Imprinting, apoptosis and impact of environmental conditions
are at the border between maternal and metabolic factors,
especially during the first division cycles. Experimental
manipulations of zygotes in the mouse have clearly proved
the necessary complementarities between the maternal and the
paternal genome to ensure normal embryonic development.
This is due to imprinting: a kind of ‘dialogue’ occurring as early
as the pronuclear stage. Chimeras can be obtained, however,
between uniparental and normal embryos. Genomic imprinting
seems to be more or less directly related to variations in the
methylation pattern of some genes. One of the most important
systems is IGF2/IGF2-R (De Groot et al., 1993). The ligand
is brought by the paternal genome and the receptor by the
maternal one. The maternal and the paternal X chromosome
are submitted to differential inactivation, related to different
methylation patterns of Xist, in the preimplantation period. Xist
is the initiator of methylation carried by the X chromosome.
The H19 gene, a tumour proliferation suppressor, is expressed
in placenta but not in the mole. Disorganized imprinting
may have harmful effects on early preimplantation and late
postimplantation development (Goshen et al., 1994).
In-vitro culture conditions and environmental
factors
These are very different from the in-vivo conditions (light,
variations in pH and temperature, static medium). Attention
has been recently focused on pathologies related to imprinting,
i.e. Angelmann and Beckwith–Wiedmann syndromes in IVF
babies (Edwards and Ludwig, 2003; Niemitz and Feinberg,
2004; Johnson 2005). It is obvious that in-vitro culture
conditions are always worse than the co-culture environment
and the in-vivo situation. Numerous observations in laboratory
animals and in ruminants have now demonstrated that serum
addition is almost certainly deleterious for the imprinting
process.

Methionine and sulphur amino acid (Figure 1)
Silent paternal alleles of H19, Igf2, Grb10 and Grb7 are
aberrantly expressed and hypomethylated in simplex media
but not media with amino acids in mouse embryos (Khosla et
al., 2001). Microarray technology has also demonstrated that
expression of 114 genes is affected in culture without amino
acids, versus 29 being mis-expressed in culture with amino acids
(Rinaudo and Schultz, 2004). Silencing of imprinted genes,
including methylation of Cdkn1c, constitutes an epigenetic
signature of cellular stress and tumorigenesis. Methionine is
classified as an ‘essential amino acid’ and thus omitted in most of
the first phase sequential media: this is a totally wrong concept,
not corresponding to the in-vivo situation, where all the amino
acids are present (i.e. in the oviduct and uterus). In fact, the
balance between methionine and the other amino acids is of
major importance. Methionine has such a high affinity for the
transporters that at too high concentrations, it may prevent the
uptake of other amino acids, thus unbalancing the endogenous
pool. Methionine is incorporated by mouse, bovine and human
embryos (Ménézo et al., 1989). It initiates all the protein synthesis
through Met-tRNA. Methionine is the fuel of methylation through
the synthesis of S-adenosyl methionine (SAM). SAM synthesis
occurs before genomic activation in the mouse and the human
embryo (Ménézo et al., 1989). SAM and other methylation
agents (group B vitamins) are the critical epigenetic regulators
which can affect DNA methylation and imprinting (Wolff et al.,
1998; Xin et al., 2003; Niemitz and Feinberg, 2004), as well as
histone H3 methylation (Xin et al., 2003; Dodge et al., 2004).
Anomalies in histone methyl transferase activity will also affect
gene silencing and then lead to cytogenetic problems and altered
DNA methylation, including Prader–Willi syndrome. Moreover,
it has to be emphasized that this CpG methylation in this PWS-
Figure 1. Methionine metabolic pathways in the embryo.
Article - Preimplantation embryo development - YJR Ménézo
1C site occurs after fertilization in humans, unlike mice, where
PWS-1C methylation occurs during oogenesis (El-Maari et al.,
2001).This aspect emphasizes again the fact that the mouse
embryo is not always a good model for humans.
Lack of sulphur amino acids leads to the SAAD
Sulphur amino acid deprivation syndrome (SAAD) induces
programmed cell death independently of caspase activation
(Lu et al., 2003). Methionine can be transformed, after uptake,
in cysteine via the trans-sulfuration pathway. Cysteine is then
a ‘partner’ in the synthesis of glutathione and hypotaurine, two
free radical scavengers of major importance in vivo (Guerin et
al., 2001). Apoptosis induced by methionine restriction induces
formation of nucleosomal DNA fragments and is mitochondria
dependant (the main source of free radical is mitochondria
metabolism). In fact, a ‘young’ oocyte may have a sufficient
endogenous pool of metabolites (i.e. methionine) to allow it to
match with a poorly balanced culture medium, but again there
are problems when ageing alters this pool. Is confirmation
required for this altered methylation process with age and
superovulation process? The paper of Chang et al. (2005)
would provide it: the Beckwith–Wiedemann syndrome seems,
in assisted reproduction, to be age and methyl-donor dependant.
It is obvious that ‘superovulation’ disturbs the endogenous pool
of the oocytes (including the amino acids, i.e. methionine) and
the resulting methylation process is impaired if the amino acid
content of the medium is not adapted.
Homocysteine in the surrounding of the embryo is deleterious, as
it induces efflux of methionine from the embryo (Ménézo et al.,
1989) and then impacts directly or indirectly on the methylation
process.
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 Article - Preimplantation embryo development - YJR Ménézo
Of major importance also is the generation of reactive oxygen
species (ROS; Agarwal, 2005). ROS are generated by various
endogenous metabolic pathways, but mainly by oxidative
phosphorylation, NADPH oxidase and xanthine oxidase, but
enhanced during in-vitro culture. The main targets for ROS-
induced decay are DNA and lipids. Lipid peroxidation leads to
major delays in cell division. Oxidation of DNA strands induces
developmental arrests and even carcinogenesis, as mentioned
earlier, but at a lower level, H2O2 formed is a mediator of
apoptosis in the embryo. Two major compounds are keys in the
culture conditions: methionine and glucose.
An excessive glucose concentration induces apoptosis: it
increases the concentration of proapoptotic factor Bax. Caspase
3 and CAD are involved in embryo toxicity of high glucose
(Pampfer, 2000; Pampfer et al., 2001). Excess glucose inhibits
the purine salvage pathway, thus increasing ROS formation.
Hyperglycaemia affects sex ratio through apoptosis towards
females in mice and cattle: this is related to the production of X-
linked XIAP (X linked inhibitor of apoptosis protein; Jimenez et
al., 2003). Typically, here, there is a strong interrelation between
endogenous factors, i.e. mRNAs and exogenous factors such as
environment and/or culture medium composition.
Conclusion
Harmonious preimplantation development avoids late
miscarriages and even more anomalies in offspring. Ideally,
it is the result of fertilization of a good oocyte by a good
spermatozoon. This ideal situation rarely occurs, as only a
quarter of sexual cycles seem to be fertile, but the embryo is
equipped with some processes allowing it to ‘repair’ or ‘correct’
some errors under a critical threshold. The more advanced the
age of the couple, the more problematic is the probability of
a suitable development allowing conceiving normal offspring.
It must also be taken into account that in-vitro environmental
conditions may have a negative impact on embryo quality,
especially in patients over 35 years, when paternal and maternal
negative influences become obvious.
References
Agarwal A 2005 Oxidative stress and its implications in female
infertility – a clinician perspective Reproductive BioMedicine
Online 11, 641–650.
Ao A, Erickson RP, Winston RM et al. 1994 Transcription of paternal
Y-linked genes in the human zygote as early as the pronucleate
stage. Zygote 2, 281–287.
Boiteux S, Radicella JP 2000 The human OGG1 gene: structure,
functions, and its implication in the process of carcinogenesis.
Archives in Biochemistry and Biophysics 377, 1–8.
Bourouillou G, Dastugue N, Colombies P 1985 Chromosome studies
in 952 infertile male with a sperm count below 10 millions/ml.
Human Genetics 71, 366–367.
Chang AS, Moley KH, Wangler M et al. 2005 Association of
Beckwith–Wiedemann syndrome and assisted reproductive
technology: a case series of 19 patients. Fertility and Sterility 83,
349–354.
Dale B, Ménézo Y, Cohen J et al. 1988 Intracellular pH regulation in
the human oocyte. Human Reproduction 13, 964–970.
De Groot N, Hochberg A 1993 Gene imprinting during placental
and embryonic development. Molecular Reproduction and
Development 36, 390–406.
Dodge JE, Kang YK, Beppu H et al. 2004 Histone H3-K9
620
methyltransferase ASET is essential for early development.
Molecular and Cellular Biology 24, 2478–2486.
Dozortsev D, Rybouchkin A, De Sutter P et al. 1995 Human oocyte
activation following intracytoplasmic injection: the role of the
sperm cell. Human Reproduction 10, 403–407.
Edwards RG, Ludwig M 2003 Are major defects in children conceived
in vitro due to innate problems in patients or to induced genetic
damage? Reproductive BioMedicine Online 7, 131–138.
El-Maarri O, Buiting K, Peery EG et al. 2001 Maternal methylation
imprints on human chromosome 15 are established during or after
fertilization. Nature Genetics, 27, 341–344.
El Mouatassim S, Guerin P, Ménézo YJR 1999 Expression of genes
encoding anti-oxidant enzymzs in human and mouse oocytes
during final stages of oocyte maturation. Molecular Human
Reproduction 5, 720–725.
Goshen R, Ben Rafael Z, Gonik B et al. 1994 The role of genomic
imprinting in implantation. Fertiity and Sterility. 62, 903–910.
Guerin P, Matillon C, Bleau G et al. 2005 Impact of sperm DNA
fragmentation on ART outcome. Gynecologie, Obstetrique et
Fertilité 33, 665–668.
Guerin P, El Mouatassim S, Ménézo YJR 2001 Oxidative stress and
protection against reactive oxygen species in the pre-implantation
embryo and its surroundings. Human Reproduction Update 7,
175–89.
Hamatani T, Falco G, Carter MG et al. 2004 Age-associated alteration
of gene expression patterns in mouse oocytes. Human Molecular
Genetics 13, 2263–2278.
Hazzouri M, Rousseaux S, Mongelard F et al. 2000 Genome
organization in the human sperm nucleus studied by FISH and
confocal microscopy. Molecular Reproduction and Development
55, 307–315.
Herubel F, El Mouatassim S, Guerin P et al. 2002 Genetic expression
of monocarboxylate transporters during human and murine oocyte
maturation and early embryonic development. Zygote 10, 175–180.
Hewitson L, Simerly C, Schatten G 2000 Cytoskeletal aspects of
assisted fertilization. Seminars in Reproductive Medicine 18,
151–159.
Janny L, Ménézo Y 1994 Evidence for a strong paternal effect on
human preimplantation embryo development and blastocyst
formation. Molecular Reproduction and Development 38, 36–42.
Jimenez A, Madrid-bury N, Fernandez R et al. 2003 Hyperglycemia-
induced apoptosis affects sex ratio of bovine and murine
preimplantation embryos. Molecular Reproduction and
Development 65, 180–187.
Johnson MH 2005 The problematic in-vitro embryo in the age of
epigenetics. Reproductive BioMedicine Online 10, 88–96.
Khosla S, Dean W, Reik W 2001 Culture of pre-implantation embryos
and its long-term effects on gene expression and phenotype.
Human Reproduction Update, 7, 419–427.
Lu S, Hoestje SM, Choo E et al. 2003 Induction of caspase dependant
and independant apoptosis in response to methionine restriction.
International Journal of Oncology 22, 415–420.
Ménézo Y, Khatchadourian Ch, Gharrib et al. 1989 Regulation of S-
adenosyl methionine Synthesis in the mouse embryo. Life Sciences
44, 1601–1609.
Morozumi K, Yanagimachi R 2005 Incorporation of the acrosome
into the oocytes during intracytoplasmic sperm injection could be
potentially hazardous to embryo development. Proceedings of the
National Academy of Sciences New York 102, 14209–14214.
Niemitz EL, Feinberg AP 2004 Epigenetics and assisted reproductive
technology: a call for investigation. American Journal of Human
Genetics 74, 599–609.
Palermo G, Munnè S, Cohen J 1994 The human zygote inherits its
mitotic potential from the male gamete. Human Reproduction 9,
1220–1225.
Pampfer S 2000 Peri-implantation embryopathy induced by maternal
diabetes. Journal of Reproduction and Fertility 55 (suppl. 1),
129–139.
Pampfer S, Vanderheyden I, Van Der Smissen P 2001 Expression and
role of Bcl-2 in rat blastocysts exposed to high D-glucose. Diabetes
50,143–149.

Renard JP, Baldacci P, Richoux-Duranthon V et al. 1994 A maternal
factor affecting mouse blastocyst formation. Development 120,
797–802.
Rinaudo P, Schultz RM 2004 Effects of embryo culture on global
pattern of gene expression in preimplantation mouse embryos
Reproduction 128, 301–311.
Rodriguez S, Goyanes V, Segrelles E et al. 2005 Critically short
telomeres are associated with sperm DNA fragmentation. Fertility
and Sterility 84, 843–845.
Ron-El R., Nachum H, Herman A et al. 1991 Delayed fertilization
and poor embryonic development associated with impaired semen
quality. Fertility and Sterility 55, 338–344.
Sakkas D, Urner F, Bianchi PG et al. 1996 Sperm chromatin
anomalies can influence decondensation after intracytoplasmic
sperm injection. Human Reproduction 11, 837–843.
Schatten G 1994 The centrosome and its mode of inheritance:
the reduction of the centrosome during gametogenesis and its
restoration during fertilization. Developmental Biology 165,
299–335.
Seli E, Lalioti MD, Flaherty SM et al. 2005 An embryonic poly(A)
binding protein (ePAB) is expressed in mouse oocytes and early
preimplantation embryo. Proceedings of the National Academy of
Sciences New York 102, 367–372.
Article - Preimplantation embryo development - YJR Ménézo
Simerly C, Wu G-J, Zoran S et al. The paternal inheritance of the
centrosome, the cells microtubule-organizing center, in humans,
and the implications for infertility. Nature Medicine 1, 47–52.
Swann K, Larman MG, Sauders CM et al. 2004 The cytosolic sperm
factor that triggers Ca2+ oscillations and egg activation in mammals
is a novel phospholipase C: PLCzeta. Reproduction 12, 431–439.
Takeuchi T, Colombero LT, Neri QV et al. 2004.Does ICSI
require acrosomal disruption? An ultrastructural study. Human
Reproduction 19, 114–117.
Wolff GL, Kodell RL, Moore SR et al. 1998 Maternal epigenetics and
methyl supplements affect agouti gene expression in Avy/mice.
FASEB Journal 12, 949–957.
Xin Z, Tachibana M, Guggiari et al. 2003 Role of histone
methyltransferase G9a in CpG methylation of the Prader–Willi
syndrome imprinting centre. Journal of Biological Chemistry 278,
14996–15000.
Received 14 November 2005; refereed 13 December 2005; accepted 2
February 2006.
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