1 Depletion On Meiotic Maturation, Cumulus Expansion, and Early Cleavage, But Did Not Rescue

http://www.biolreprod.org/content/91/1/7.abstract?
sid=6b2218a6-de2a-41dc-9495-838530f782b0
ABSTRACT
Autophagy is a dynamically regulated intracellular degradation system that is important for cellular
processes such as amino acid production during starvation and intracellular quality control.
Previously, we reported that autophagy is suppressed in oocytes but is rapidly up-regulated after
fertilization. During this period, autophagy is thought to be important for the generation of amino
acids from the bulk degradation of maternal proteins that have accumulated during oogenesis.
However, the mechanism of autophagy induction after fertilization is presently unknown.
http://www.biolreprod.org/content/90/4/83.abstract?sid=1076d5cd-c450-4395-90db-9ca5af56d494
Zinc is an essential nutrient for optimal fertility, but the effects of preconception zinc deficiency on
postimplantation development are not known. Female mice were fed a control or a zinc-deficient
diet (ZDD) for 45 days before ovulation (preconception). Embryonic and/or placental development
were evaluated on Days 3.5, 6.5, 10.5, 12.5, and 16.5 of pregnancy. The findings show a decrease in
embryo length (31%, Day 10.5; 13%, Day 12.5; 10%, Day 16.5) and weight (23%, Day 16.5) in
embryos from mothers fed a ZDD preconception.Collectively, the findings provide evidence for the
importance of preconception zinc in promoting optimal fertility and oocyte developmental potential.
The preimplantation period is a time of reprogramming that may be vulnerable to disruption. This
question has wide clinical relevance since the number of children conceived by in vitro fertilization
(IVF) is rising. These studies demonstrate that adult metabolism is affected by the type of
conditions encountered during the preimplantation stage. Further, the postnatal growth trajectory
and glucose homeostasis following ex vivo manipulation may be sexual dimorphic. Future work on
the long-term effects of IVF offspring should focus on glucose metabolism and the cardiovascular
system.
Oocyte-expressed genes regulate key aspects of ovarian follicular development and early
embryogenesis.
Depletion of JY-1 protein during IVM effectively reduced cumulus expansion, percentage of
oocytes progressing to metaphase II, proportion of embryos that cleaved early, total cleavage rates
and development to 8- to 16-cell stage, and totally blocked development to the blastocyst stage
relative to controls. Supplementation with JY-1 protein during oocyte culture rescued effects of JY1 depletion on meiotic maturation, cumulus expansion, and early cleavage, but did not rescue
development to 8- to 16-cell and blastocyst stages.
Assisted reproductive technologies (ART) have enabled millions of couples with compromised
fertility to conceive children. Nevertheless, there is a growing concern regarding the safety of these
procedures due to an increased incidence of imprinting disorders, premature birth, and low birth
weight in ART-conceived offspring. An integral aspect of ART is the oxygen concentration used
during in vitro development of mammalian embryos, which is typically either atmospheric (20%)
or reduced (5%). Both oxygen tension levels have been widely used, but 5% oxygen improves
preimplantation development in several mammalian species, including that of humans. To
determine whether a high oxygen tension increases the frequency of epigenetic abnormalities in
mouse embryos subjected to ART, we measured DNA methylation and expression of several
imprinted genes in both embryonic and placental tissues from concepti generated by in vitro
fertilization (IVF) and exposed to 5% or 20% oxygen during culture. Although culturing embryos
in both of the oxygen concentrations resulted in a significant increase of epigenetic defects in
placental tissues compared to naturally conceived controls, we did not detect significant differences
between embryos cultured in 5% and those cultured in 20% oxygen. T
The global chromatin configuration is dramatically remodeled during fertilization and early
preimplantation development. Although the chromocenters, which are pericentromeric
heterochromatin clusters, are observed in the nuclei of oocytes, they disappear after fertilization and
then reappear at the four-cell stage.
http://www.biolreprod.org/content/89/5/124.abstract?sid=084996e6-b926-4f06-8582-d6c0d9db5cf2
Accumulating evidence indicates that cellular and molecular abnormalities occur during oocyte
aging, including fragmentation, increases in intracellular reactive oxygen species (ROS), and
abnormal Ca2+ oscillations. We conclude that the increased intracellular ROS damaged the ER
clusters and ER Ca2+ homeostasis, resulting in a disorder in ooplasmic free Ca2+, which caused the
fragmentations seen in porcine MII oocytes during aging.
During embryo culture, ammonium is generated by amino acid metabolism and from the
spontaneous deamination of amino acids at 37C. Whilst 20% oxygen represents a source of stress
to the developing embryo, it is not known how oxygen affects the physiology of the embryo in the
presence of other sources of stress.
Data reveal that both oxygen and ammonium affect amino acid utilization by the developing
embryo, however, 20% oxygen appears to have the greater impact. Mouse blastocysts can alleviate
ammonium stress by its transamination to both glutamine and alanine, but only under physiological
conditions.
Mice and cattle use distinct pathways for the first cell segregation into inner cell mass (ICM) and
trophectoderm (TE) lineages at the blastocyst stage.
As a result, we identified seven ICM-dominant genes and five TE-dominant genes not found in
earlier studies. Our findings provide novel insights into the mechanism of cell-fate specification in
the pre-implantation bovine embryo.
http://www.biolreprod.org/content/87/2/34.abstract?sid=203f97ed-c5a7-4850-bf32-29f7bba5e7ab
It has been reported that suboptimal in vitro culture (IVC) of mouse embryos can affect the
postnatal expression of epigenetically sensitive alleles, resulting in altered postnatal growth, organ
dimensions, health, and behavior in the offspring. Although these detrimental impacts on the
offspring are well described, the relative contribution of the IVC-produced fathers is unclear. In this
work, we have analyzed if suboptimal IVC (achieved by altering the culture medium by the addition
of FCS) can affect male fertility and if organ size and glucose clearance, two of the adverse effects
produced by suboptimal IVC conditions, were transmitted to the next two generations. IVCproduced males had lower sperm concentrations (5.8 106 spermatozoa in IVC vs. 14.5 106
spermatozoa in control), and these sperm exhibited decreased overall motility (49.6% vs. 72.8% in
control) and progressive motility (22.6% vs. 32.2% in control). Suboptimal IVC reduced the
expression of Kap1, Sox2, Hdac1, Dnmt1, and Dnmt3a, suggesting a molecular epigenetic role for
gene expression modifiers in the origin and transmission of these abnormal phenotypes.
Oxygen is a powerful regulator of preimplantation embryo development, affecting gene expression,
the proteome, and energy metabolism. Even a transient exposure to atmospheric oxygen can have a
negative impact on embryo development, which is greatest prior to compaction, and subsequent
postcompaction culture at low oxygen cannot alleviate this damage. In spite of this evidence, the
majority of human in vitro fertilization is still performed at atmospheric oxygen. One of the
physiological parameters shown to be affected by the relative oxygen concentration, carbohydrate
metabolism, is linked to the ability of the mammalian embryo to develop in culture and remain
viable after transfer. The aim of this study was, therefore, to determine the effect of oxygen
concentration on the ability of mouse embryos to utilize both amino acids and carbohydrates both
before and after compaction. Metabolomic and fluorometric analysis of embryo culture media
revealed that when embryos were exposed to atmospheric oxygen during the cleavage stages, they
exhibited significantly greater amino acid utilization and pyruvate uptake than when cultured under
5% oxygen. In contrast, postcompaction embryos cultured in atmospheric oxygen showed
significantly lower mean amino acid utilization and glucose uptake. These metabolic changes
correlated with developmental compromise because embryos grown in atmospheric oxygen at all
stages showed significantly lower blastocyst formation and proliferation. These findings confirm
the need to consider both embryo development and metabolism in establishing optimal human
embryo growth conditions and prognostic markers of viability, and further highlight the impact of
oxygen on such vital parameters.
http://www.biolreprod.org/content/86/1/1.11.abstract?sid=203f97ed-c5a7-4850-bf32-29f7bba5e7ab
The implantation process begins with attachment of the trophectoderm (TE) of the blastocyst
to the maternal endometrial epithelium. Herein we have investigated the transcriptome of
mural TE cells from 13 human blastocysts and compared these with those of human
embryonic stem cell (hESC)-derived-TE (hESCtroph). The transcriptomes of hESCtroph at
Days 8, 10, and 12 had the greatest consistency with TE. Among genes coding for secreted
proteins of the TE of human blastocysts and of hESCtroph are several molecules known to be
involved in the implantation process, as well as novel ones, such as CXCL12, HBEGF, inhibin
A, DKK3, WNT5A, and follistatin. The similarities between the two lineages underscore some
of the known mechanisms and offer discovery of new mechanisms and players in the process
of the very early stages of human implantation. We propose that the hESCtroph is a viable
functional model of human trophoblasts to study trophoblast-endometrial interactions.
Furthermore, the data derived herein offer the promise of novel diagnostics and therapeutics
aimed at practical challenges in human infertility and pregnancy disorders associated with
abnormal embryonic implantation.
The permeability of cells is important for cryopreservation. Previously, we showed in mice
that the permeability to water and cryoprotectants of oocytes and embryos at early cleavage
stages (early embryos) is low because these molecules move across the plasma membrane
predominantly by simple diffusion through the lipid bilayer, whereas permeability of morulae
and blastocysts is high because of a water channel, aquaporin 3 (AQP3)

Preimplantation mouse embryos of many strains become arrested at the 2-cell stage if the
osmolarity of culture medium that normally supports development to blastocysts is raised to
approximately that of their normal physiological environment in the oviduct. Arrest can be
prevented if molecules that serve as organic osmolytes are present in the medium, because
organic osmolytes, principally glycine, are accumulated by embryos to provide intracellular
osmotic support and regulate cell volume.
Sox2 is a key gene that controls transcriptional networks required for pluripotency. The role of Sox2
in the developmental transition of a highly differentiated oocyte to totipotent blastomeres of the
early preimplantation embryo, however, is not known. We report that Sox2, which is localized in the
nucleus, is first zygotically expressed during the 2-cell stage and that its expression dramatically
increases between the morula and blastocyst stages. Injecting a cRNA encoding Sox2 into 1-cell
embryos resulted in overexpression of SOX2 by approximately 70% and developmental arrest at the
2-cell stage, whereas injecting cRNAs encoding Pou5f1, Myc (also known as c-Myc), or Klf4 has
little effect on the ability of 2-cell embryos to cleave to the 4-cell stage. Furthermore,
overexpressing a dominant-negative SOX2 perturbs reprogramming of gene expression in 2-cell
embryos, though to a much lesser extent than that observed following overexpression of SOX2, and
leads to developmental failure after the 2-cell stage but before the 8-cell stage. Results of these
experiments implicate Sox2 as a critical transcriptional regulator in the oocyte-to-embryo transition
that entails formation of totipotent blastomeres and indicate that the amount of Sox2 is critical for
successful execution of this transition.
http://www.biolreprod.org/content/84/4/790.full
Our results provide an important resource for deciphering the molecular pathways driving proper
germ cell development and sex determination and will improve our understanding of the etiology of
human germ cell tumors that arise from dysregulation of germ cell differentiation
http://www.biolreprod.org/content/84/4/790/suppl/DC1!!!!!
http://www.biolreprod.org/content/83/5/859.abstract?sid=f3d9b312-33f0-4260-8d29-7a9543a48562
The regulatory influence of adiponectin on glucose metabolism of blastocysts may be of specific
interest in pathophysiological situations, such as obesity during pregnancy. Since the discovery of
adipokines, the adipose tissue is no longer considered to be an inactive fat storage. It secretes a
variety of bioactive molecules, which regulate body metabolism and energy homeostasis. One of
these molecules is the adipokine adiponectin. In different tissues, adiponectin triggers metabolic
effects through the adenosine monophosphate-activated protein kinase (PRKA), which is a master
regulator in glucose and lipid metabolism.
These results suggest that elevated concentrations of progesterone do not affect the ability of the
early embryo to reach the blastocyst stage in vivo but do result in subtle changes to the
transcriptome of the embryo that may be associated with advanced elongation posthatching.
This study describes a temporal profile of gene expression from normal human fetal testes and
ovaries. Gonads from 34 fetuses between 9 wk and 20 wk of gestation were obtained from the
Department of Pathology and the Birth Defects Research Laboratory at the University of
Washington. Relative transcript levels were determined using the Affymetrix Human Genome
U133A Plus 2.0 arrays. Sex determination occurs in the human gonad at 6 wk of gestation with
development of the testis driven by expression of SRY. In this study, SRY transcript was present and
elevated at 9 wk of gestation in the testis but was absent in the ovary. The transcript levels of other
testis-specific factors SOX9 and AMH and the steroidogenic genes CYP17A1, CYP11A1, STAR, and
HSD17B3 were all significantly higher in the testis. In contrast, transcripts known to be involved in
meiosis, including STRA8, SPO11, SYCP3, TEX11, TEX14, and STAG3, showed highest expression
in the fetal ovary beginning at Week 12. These gene expression profiles will be a resource for
understanding and defining normal gonad development and provide the opportunity to dissect
abnormal development.
http://www.biolreprod.org/content/80/3/493.abstract?sid=1e27822e-001e-4f49-b2cd-74f279c20950
Acting together, alteration in Ca2+ oscillations and decrease in BCL2 expression in in vitro-aged
oocytes may lead to poor embryo development.
These results suggest that impaired metabolism of glucose in the blastocyst via the MAS alters the
ability of the embryos to implant and form a pregnancy and leads to reduced fetal weight, likely via
altered placental development and function.
Mouse embryos display a strain-dependent propensity for blastomere cytofragmentation at
the two-cell stage. The maternal pronucleus exerts a predominant, transcription-dependent
effect on this phenotype, with lesser effects of the ooplasm and the paternal pronucleus. A
parental origin effect has been observed as an inequality in the cytofragmentation rate of
embryos produced through genetic crosses of reciprocal F1 hybrid females. These results are
relevant to our understanding of the mechanisms of epigenetic effects on development and the
possible fertility effects of genetic and epigenetic interactions in reproductive medicine.
http://www.biolreprod.org/content/79/4/618.abstract?sid=1e27822e-001e-4f49-b2cd74f279c20950
Restricting the growth of the embryo can cause adverse whole-of-life changes in an
organism's homeostasis. Such adverse long-term consequences may occur even when growth
restriction occurs only during the preimplantation period. The molecular basis for these longterm effects has not been defined, although an epigenetic mechanism is suspected. Some loci
seem to be more sensitive to epigenetic perturbation than others .
These results show for the first time that the preimplantation embryo's growth environment
can affect the postnatal expression of a defined epigenetically sensitive allele.
http://www.biolreprod.org/content/78/2/299.abstract?sid=0f1fcc50-13cb-4d0b-8da6534c0b27ccce
Poor maternal nutrition during pregnancy can alter postnatal phenotype and increase
susceptibility to adult cardiovascular and metabolic diseases. However, underlying
mechanisms are largely unknown. Here, we show that maternal low protein diet (LPD), fed
exclusively during mouse preimplantation development, leads to offspring with increased
weight from birth, sustained hypertension, and abnormal anxiety-related behavior, especially
in females. These adverse outcomes were interrelated with increased perinatal weight being
predictive of later adult overweight and hypertension. Embryo transfer experiments revealed
that the increase in perinatal weight was induced within blastocysts responding to
preimplantation LPD, independent of subsequent maternal environment during later
pregnancy. We further identified the embryo-derived visceral yolk sac endoderm (VYSE) as
one mediator of this response. VYSE contributes to fetal growth through endocytosis of
maternal proteins, mainly via the multiligand megalin (LRP2) receptor and supply of
liberated amino acids. Thus, LPD maintained throughout gestation stimulated VYSE nutrient
transport capacity and megalin expression in late pregnancy, with enhanced megalin
expression evident even when LPD was limited to the preimplantation period. Our results
demonstrate that in a nutrient-restricted environment, the preimplantation embryo activates
physiological mechanisms of developmental plasticity to stablize conceptus growth and
enhance postnatal fitness. However, activation of such responses may also lead to adult excess
growth and cardiovascular and behavioral diseases.
http://www.biolreprod.org/content/74/5/881.abstract?sid=692d5bb1-1e15-4f8e-afbbbe35e4111611
Glucose concentration during cumulus-oocyte complex (COC) maturation influences several
functions, including progression of oocyte meiosis, oocyte developmental competence, and cumulus
mucification. Glucosamine (GlcN) is an alternative hexose substrate, specifically metabolized
through the hexosamine biosynthesis pathway, which provides the intermediates for extracellular
matrix formation during cumulus cell mucification.
Our data are the first to link hexosamine biosynthesis, involved in cumulus cell mucification, to
oocyte developmental competence during in vitro maturation.
http://www.biolreprod.org/content/74/5/865.abstract?sid=692d5bb1-1e15-4f8e-afbb-be35e4111611
This study investigated the effects on fertilized embryo development of somatic cytoplasm after its
injection into intact mouse oocytes
Here, we report for the first time that somatic cytoplasm causes abnormal placentas in fertilized
embryos. This study suggests that somatic cell cytoplasmic material is one cause of the low rate of
full-term development in cloned mammals.
http://www.biolreprod.org/content/74/3/538.abstract?sid=cc50bded-627c-45eb-993e-1f081896fbd5
It is generally accepted that preeclampsia results from reduction in perfusion to the uteroplacental
unit leading to maternal hypertension and fetal growth restriction. Placental insufficiency creates an
environment of fetal undernutriton, predisposing the fetus to the development of adult disease.
Further, exposure to placental insufficiency during late gestation leads to developmental alterations
characterized by vascular hyperresponsiveness, perpetuated to a second generation of offspring in
the absence of persistent environmental stimuli, contributing to hypertension.
http://www.biolreprod.org/content/74/2/288.abstract?sid=cc50bded-627c-45eb-993e-1f081896fbd5
The presence of ammonium in culture medium has a detrimental effect on embryo physiology and
biochemistry; however, the stage at which the embryo is most sensitive to this effect is unknown.
This raises the possibility that the later stage embryo is more able to protect itself from in vitroderived stress and that the majority of in vitro-induced damage to mouse embryos is inflicted at the
early stages of development.
http://www.biolreprod.org/content/73/6/1094.abstract?sid=cc50bded-627c-45eb-993e1f081896fbd5
Transforming growth factor alpha (TGFA) is produced by epithelial cells in the oviducts and uteri
and has the potential to act as an anti-apoptotic factor on preimplantation embryos expressing its
receptor. Previously, we demonstrated that survivin (also known as BIRC5), an anti-apoptotic gene
expressed in mouse preimplantation embryos, protects embryos from apoptosis.
These data suggest that survivin contributes to the anti-apoptotic activities of TGFA in blastocysts.
We also found that the upregulation of survivin expression was mediated by activation of the
phosphatidylinositol 3-kinase (PI3K) signaling pathway. Thus, TGFA inhibits apoptosis in mouse
blastocysts through upregulation of survivin expression via the PI3K pathway.
http://www.biolreprod.org/content/72/6/1359.abstract?sid=6485611a-898b-45ce-bdee192ef907740e
DNA repair is essential for maintaining genomic integrity, and may be required in the early embryo
to correct damage inherited via the gametes, damage that arises during DNA replication, or damage
that arises in response to exposure to genotoxic agents. The capacity of preimplantation stage
mammalian embryos to repair damaged DNA has not been well characterized.
This effect of in vitro culture on nonhuman primate embryos may be relevant to assessing the
potential advantages and disadvantages of prolonged in vitro culture of human embryos.
http://www.biolreprod.org/content/69/4/1109.abstract?sid=93b844ce-9f32-418e-87d57d8eb52d4846
The presence of ammonium in the culture medium has significant detrimental effects on the
regulation of embryo physiology and genetics. Ammonium levels build up linearly over time in the
culture medium when media containing amino acids are incubated at 37C. Ammonium in the
culture media significantly reduces blastocyst cell number, decreases inner cell mass development,
increases apoptosis, perturbs metabolism, impairs the ability of embryos to regulate intracellular
pH, and alters the expression of the imprinted gene H19 .
http://www.biolreprod.org/content/68/6/2073.abstract?sid=d1da91b8-a37e-468b-b5e3276bade6dbaa
Results show that expression of developmentally important genes is related to the two cell lineages
in the early embryo and emphasize the critical role of a well controlled spatial gene expression
pattern for regular preimplantation development.
For minimal and moderate levels of fragmentation, the reduction in cell numbers was confined
largely to the trophectoderm and a steady number of inner cell mass cells was maintained. However,
with extensive fragmentation of more than 25%, cell numbers in both lineages were reduced in the
few embryos that formed blastocysts. Apoptotic nuclei were present in both the trophectoderm and
inner cell mass, with the lowest incidence in blastocysts that had developed from embryos with
minor (510%) fragmentation. Paradoxically, higher levels of apoptosis were seen in embryos of
excellent morphology, suggesting a possible role in regulation of cell number.
Coculture of 10 two-cell bovine embryos with bovine oviductal epithelial cells increased the
development of the embryos into blastocysts.
GAMETES
http://www.biolreprod.org/content/90/6/125.abstract?sid=7f461e87-1289-4986-b4a0-d5a14f504d1e
In conventional in vitro fertilization (IVF), complete failure of fertilization occurs in 5% to 15% of
treatments. Although the causes may be unclear, sperm defects appear to be the major contributor.
However, a convincing test is not yet available that can predict the risk of fertilization failure. In
this study, we found that germinal angiotensin-converting enzyme (gACE) (also called testicular
ACE) was undetectable in sperm from patients who had total fertilization failure (TFF) and lower
fertilization rates (LFRs) by IVF based on Western blot and indirect immunofluorescence analyses.
We conclude that sperm lacking gACE may be recognized before commencing IVF and that the
patients may be directed instead to consider intracytoplasmic sperm injection.
http://www.biolreprod.org/content/90/4/73.abstract?sid=3354223c-bd56-487b-948c-1e447614bb71
Previous reports have demonstrated that embryonic stem cells were capable of differentiating into
primordial germ cells through the formation of embryoid bodies that subsequently generated
oocyte-like cells (OLCs). Such a process could facilitate studies of primordial follicle oocyte
development in vitro and regenerative medicine.
Although the in vitro maturation and fertilization potentials are as yet unproven, short-term (<25
days) and high-efficiency (>2%) derivation of OLCs from hAFSCs might provide a new approach
to the study of human germ cell development in vitro.
http://www.biolreprod.org/content/88/6/164.abstract?sid=7f461e87-1289-4986-b4a0-d5a14f504d1e
Metabolic conditions characterized by elevated free fatty acid concentrations in blood and follicular
fluid are often associated with impaired female fertility.
We propose that the involvement of high levels of mobilized oleic acid in follicular fluid in
combination with the induced lipid storage in cumulus cells serves to prevent harmful saturated
fatty acid exposure to the oocyte.
http://www.biolreprod.org/content/88/3/67.abstract?sid=f30999e1-c64d-4efe-af26-1cc618bed72f
Melatonin Prevents Postovulatory Oocyte Aging in the Mouse and Extends the Window for
Optimal Fertilization In Vitro
The quality of metaphase II oocytes deteriorates rapidly following ovulation as the result of an
aging process associated with impaired fertilizing potential, disrupted developmental competence,
and increased likelihood of embryonic resorption. Because oxidative stress accelerates the onset of
apoptosis in oocytes and influences their capacity for fertilization, this study aimed to characterize
the significance of such stress in the postovulatory aging of mouse oocytes in vitro. We investigated
the ability of the potent antioxidant melatonin to arrest the aging process when used to supplement
oocyte culture medium. This study demonstrated that oxidative stress may occur in oocytes after as
little as 8 h in culture and coincides with the appearance of early apoptotic markers such as
phosphatidylserine externalization, followed 16 h later by caspase activation (P < 0.05) and
morphological evidence of oocyte senescence. We conclude that melatonin may be a useful tool in a
clinical setting to prevent the time-dependent deterioration of oocyte quality following prolonged
culture in vitro.
http://www.biolreprod.org/content/87/4/89.abstract?sid=f30999e1-c64d-4efe-af26-1cc618bed72f
The degree of expansion and expression of cumulus matrix genes are positively correlated with
oocyte quality, suggesting that this matrix plays a key role in oocyte maturation. Based on
recognized filtration properties of analogous matrices, we investigated whether the cumulus matrix
acts as a molecular filter.
This is the first demonstration of a biophysical property of the cumulus matrix.
http://www.biolreprod.org/content/87/1/11.abstract?sid=148393c2-6008-4edc-959d-4e3f375fdad2
These results establish zinc as a crucial regulator of meiosis throughout the entirety of oocyte
maturation, including the maintenance of and release from the first and second meiotic arrest points.
http://www.biolreprod.org/content/86/1/1.4.abstract?sid=148393c2-6008-4edc-959d-4e3f375fdad2
Disruptions in the regulatory pathways controlling sex determination and differentiation can cause
disorders of sex development, often compromising reproductive function. Although extensive
efforts have been channeled into elucidating the regulatory mechanisms controlling the many
aspects of sexual differentiation, the majority of disorders of sex development phenotypes are still
unexplained at the molecular level. In this study, we have analyzed the potential involvement of
Wnt5a in sexual development and show in mice that Wnt5a is male-specifically upregulated within
testicular interstitial cells at the onset of gonad differentiation. Homozygous deletion of Wnt5a
affected sexual development in male mice, causing testicular hypoplasia and bilateral
cryptorchidism despite the Leydig cells producing factors such as Hsd3b1 and Insl3.
http://www.biolreprod.org/content/85/5/1025.abstract?sid=4235bb35-a8ba-44ad-8da9-f748ffa992ea
In mammals, female meiosis consists of two asymmetric cell divisions, which generate a large
haploid oocyte and two small polar bodies. Asymmetric partitioning of the cytoplasm results from
migration of the meiotic spindle toward the cortex and requires actin filaments. However, the
subcellular localization and the role of the existing two cytoplasmic actin (CYA) isoforms, beta and
gamma, have not been characterized.
We show that beta- and gamma-CYA are differentially distributed in the maturing oocyte from late
metaphase I as well as in preimplantation embryos. Gamma-CYA is preferentially enriched in
oocyte cortices and is absent from all cell-cell contact areas from metaphase II until the blastocyst
stage. Beta-CYA is enriched in contractile structures, at cytokinesis, at cell-cell contacts, and around
the forming blastocoel. Alteration of beta- or gamma-CYA function by isoform-specific antibody
microinjection suggests that gamma-CYA holds a major and specific role in the establishment
and/or maintenance of asymmetry in meiosis I and in the maintenance of overall cortical integrity.
In contrast, beta- and gamma-CYA, together, appear to participate in the formation and the cortical
anchorage of the second meiotic spindle in waiting for fertilization. Finally, differences in gammaCYA expression are amongst the earliest markers of cell fate determination in development
http://www.biolreprod.org/content/83/4/525.abstract?sid=7b5aa783-8ce2-40d3-9f83-e2904b692964
Cumulus-Oocyte Complexes from Small Antral Follicles During the Early Follicular Phase of
Menstrual Cycles in Rhesus Monkeys Yield Oocytes That Reinitiate Meiosis and Fertilize In Vitro
Follicle-stimulating hormone (FSH) and oocyte-secreted factors influence granulosa cell
differentiation and follicle development. Whereas FSH stimulates the expression of mural cell
transcripts, oocyte-secreted factors regulate specific cumulus cell genes and suppress the
appearance of mural cell transcripts. This study addresses the extent to which clinically relevant
changes in FSH doses applied during antral follicle development in vitro could alter the expression
of oocyte and cumulus cell transcripts. These results demonstrate that a 2.5-fold increase in FSH
changes both oocyte and cumulus cell transcript levels. Conversely, a decrease in FSH does not
affect transcript levels but seems to limit inappropriate Lhcgr expression. Modulating FSH within
physiological ranges during the antral phase of culture alters cumulus cell differentiation.
Extracellular matrix (ECM) formation by cumulus cells is an important process that determines
fertilization and embryo quality. Several collagen types are present in the ovarian follicular ECM
and are related to proliferation, steroidogenesis, and luteinization. The study revealed that exposure
to 100 IU/L FSH, as in both superovulation conditions, significantly influenced the follicle
morphology and slowed down nuclear maturation and mucification (P < 0.05). This coincided with
an increased expression of the three collagens in the cumulus-oocyte complex at the end of antral
growth and in the first hours following the ovulatory dose of human chorionic gonadotropin (P <
0.05). The increased expression might reflect a differentiation but is most likely due to a precocious
luteinization of the cumulus. Growth in HP-hMG resulted in higher Tgfb1 mRNA and protein
levels, fewer COCs with an increased collagen expression and with a more synchronous nuclear
maturation. This suggests that the presence of luteinizing hormone activity tempered the effect of
the elevated FSH dose.
http://www.biolreprod.org/content/77/5/872.abstract?sid=4f6c5255-0265-4c3e-baea-acc5db152daa
Continuous exposure of follicles/oocytes to elevated levels of insulin compromises embryonic
developmental competence, although the underlying cellular mechanisms are unknown.
These results demonstrate that oocytes contain a functional insulin signaling pathway, and that
insulin exposure during oocyte growth results in chromatin remodeling aberrations. These findings
begin to elucidate the mechanisms by which chronic elevated insulin influences oocyte meiosis,
chromatin remodeling, and embryonic developmental competence.
http://www.biolreprod.org/content/73/5/1025.abstract?sid=054253eb-8cbc-45a7-9f980bb59ba8b00e
The results strongly suggested that CCs accelerated the aging progression of both in vivo-matured
and in vitro-matured mouse oocytes.
,,femeile hioperestrogenice ar putea intra in menopauza mai rapid?
http://www.biolreprod.org/content/70/5/1263.abstract?sid=4ed3b186-8425-4d1b-be92ff247a29a386
To better understand the role of estrogen in maintaining developmental competence of mammalian
oocytes, we studied the Aromatase knockout (ArKO) mouse, which has been genetically engineered
to be incapable of synthesizing endogenous estrogen. Previous studies have established that ArKO
female mice are anovulatory with ovaries that progressively degenerate, developing hemorrhagic
cystic follicles. In young ArKO females, however, apparently healthy follicles and oocytes have
been observed. We investigated if these oocytes could be induced to ovulate, then mature, fertilize,
and develop in vitro. Following a standard superovulation protocol, ArKO oocytes did not ovulate.
When recovered manually from the ovary, however, ArKO oocytes successfully progressed through
in vitro maturation, fertilization, and development to the blastocyst stage at the same rate as wildtype and heterozygote littermates. Therefore, it appears that estrogen is not required for the
production and growth of oocytes capable of maturation and complete preimplantation development
but is required for continued follicle growth and feedback regulation of ovulation.
http://www.biolreprod.org/content/69/4/1408.abstract?sid=289588ac-f6a6-41eb-949d07b31e47ce21
Progesterone (P) appears to stimulate sperm capacitation and/or induce the acrosome reaction (AR)
in some species.
http://www.biolreprod.org/content/69/2/535.abstract?sid=289588ac-f6a6-41eb-949d-07b31e47ce21
These results demonstrate that men with severe oligozoospermia have an elevated risk for
chromosome abnormalities in their sperm, particularly sex chromosome abnormalities.
http://www.biolreprod.org/content/67/3/967.abstract?sid=289588ac-f6a6-41eb-949d-07b31e47ce21
The selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) accounts for almost
the entire selenium content of mammalian testis. PHGPx is abundantly expressed in spermatids as
active peroxidase but is transformed to an oxidatively inactivated protein in mature sperm, where it
is a major constituent of the mitochondrial capsule in the midpiece. Male infertility in seleniumdeficient animals, which is characterized by impaired sperm motility and morphological midpiece
alterations, is considered to result from insufficient PHGPx content.
http://www.biolreprod.org/content/66/2/495.abstract?sid=666bf168-eaa0-4354-a1c0-ebbf9141c55f
These results clearly show that postovulatory aging of mouse oocytes decreases reproductive fitness
and longevity of offspring.
http://www.biolreprod.org/content/65/1/141.abstract?sid=d25428dd-0ab1-4552-8fb2-62aba1f7e630
Although several studies suggest aging females may ovulate aged or overripened oocytes, these data
support the hypothesis that old females ovulate an increased percentage of atretic/apoptotic oocytes
coming from rescued follicles that would have become atretic earlier in life.
http://www.biolreprod.org/content/59/1/100.abstract?sid=d78b0172-65b3-4015-a8f0-8cd5c47bcc4d
The purpose of this study was to determine whether chromosomes in the first polar body can
participate in normal embryonic development. In the mouse the majority of first polar bodies
degenerate soon after ovulation, but a few remain viable for 10 h or more. When the contents of a
live polar body were injected into an enucleated mature oocyte and examined 2 h later, the polar
body chromosomes were arranged on a metaphase plate as seen prior to the secondary meiotic
division. Such oocytes were fertilized normally by sperm injection. When 2-cell embryos were
transferred to foster females, 3057% developed into fertile offspring. This outcome supports a
long-standing belief that chromosomes ejected into the first polar body have the same genetic
potential as those remaining in the oocyte after the first meiotic division. As the chromosomes in the
second polar body are known to have full potential to participate in normal embryonic development,
it is theoretically possible to reproduce four offspring by using chromosomes in one oocyte.

1 Depletion On Meiotic Maturation, Cumulus Expansion, and Early Cleavage, But Did Not Rescue

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1 Depletion On Meiotic Maturation, Cumulus Expansion, and Early Cleavage, But Did Not Rescue

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http://www.biolreprod.org/content/91/1/7.abstract?

and blastocysts is high because of a water channel, aquaporin 3 (AQP3)

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