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Reproduction among individuals with idiopathic/cryptogenic epilepsy: risk factors for reduced fertility in marriage.

PURPOSE: We wished to determine risk factors for reduced fertility in marriage in men and women with idiopathic/cryptogenic epilepsy and to relate rates of reproduction to the risk of epilepsy in offspring of affected individuals. METHODS: We determined history of pregnancy and child bearing among 863 adults with idiopathic/cryptogenic epilepsy (ascertained from voluntary organizations) who had been married at some time in their lives and from their same-sex siblings without epilepsy who had been married. We examined the effects of seizure type, age at onset, and family history of epilepsy on fertility. Fertility rates were measured as live births per person-year of marriage before and after onset of epilepsy and compared with fertility rates among same-sex siblings without epilepsy by incidence rate ratios (IRR). RESULTS: For both men and women with epilepsy, reduced fertility was observed after, but not before, onset of epilepsy. Among both men and women with epilepsy, those with partial onset and early age at onset (< 10 years) were more reproductively disadvantaged than those with generalized onset and later age at onset. Among those with epilepsy, men with a family history of epilepsy were less reproductively disadvantaged than men without a family history of epilepsy, whereas women with and without a family history of epilepsy did not differ. CONCLUSIONS: We found no evidence of selectively reduced fertility among men with a genetic susceptibility to epilepsy that could account for the higher risk of epilepsy among offspring of affected women than among offspring of affected men.

Adult↗

The significance of platelet-activating factor and fertility in the male primate: a review.

Since its discovery nearly 30 years ago platelet-activating factor (PAF) has emerged as one of the more important lipid mediators known. PAF (1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphorylcholine) exists endogenously as a mixture of molecular species with structural variants of the alkyl moiety. PAF is a novel potent signaling phospholipid that has unique pleiotropic biological properties in addition to platelet activation. PAF also plays a significant role in reproduction and is present in the sperm of a number of primate species. PAF content in squirrel monkey sperm is significantly higher during the breeding season than the non-breeding season. PAF content in rhesus sperm has a significant relationship with sperm motility. PAF content in human sperm has a positive correlation with seminal parameters and pregnancy outcomes. The enzymes (lyso-PAF-acetyltransferase and PAF-acetylhydrolase) necessary for PAF activation and deactivation are present in primate sperm. PAF-acetylhydrolase may act as a "decapacitation factor". Removal of this enzyme during capacitation promotes PAF synthesis increasing primate motility and fertilization. PAF also plays a significant role in the fertilization process, enhancing the fertilization rates of oocytes. Enhanced embryo development has also been reported in oocytes fertilized with PAF-treated sperm. Exogenous PAF will also significantly improve primate artificial insemination pregnancy outcomes. PAF antagonists inhibit sperm motility, acrosome reaction, and fertilization thus suggesting the presence of receptors for PAF. The PAF-receptor is present on primate sperm, with altered transcript levels and distribution patterns on abnormal cells. Whereas, the exact mechanism of PAF in sperm function and reproduction is uncertain, its importance in normal primate fertility is substantial.

Animals↗

Effect of sperm antibodies in males on human in vitro fertilization (IVF).

The effect of sperm antibodies on the human fertilization process was evaluated by analyzing the Royal Women's Hospital in vitro fertilization (IVF) data. The results suggest that sperm autoantibodies, particularly those of IgA immunoglobulin class (determined by immunobead test (IBT] can interfere with IVF. Thus, in a group (n = 8) of couples where the male partner had 80% or more of his motile spermatozoa coated with IgG and IgA class sperm antibodies, an overall fertilization rate of only 27% (18/66 ova) was obtained. In contrast, in a group (n = 9) with positive IBT results, but with less than 80% of motile spermatozoa coated with IgA class antibodies, a normal fertilization rate of 72% (47/65 ova) was obtained. Three of these patients had 90% or more of their motile spermatozoa coated with IgG and less than 70% coated with IgA class antibodies. In this subgroup a good fertilization rate of 16/21 (76%) was obtained. Another observation derived from this investigation is that the oocytes that do fertilize in the presence of sperm antibodies can subsequently proceed with normal cleavage, implantation, and pregnancy. This provides a rationale for attempting to treat these patients by reducing the proportion of antibody-coated sperm in vitro for future IVF cycles.

Autoantibodies↗

Gonadal damage and options for fertility preservation in female and male cancer survivors.

It is estimated that in 2010, 1 in every 250 adults will be a childhood cancer survivor. Today, oncological surgery, radiotherapy and chemotherapy achieve relatively high rates of remission and long-term survival, yet are often detrimental to fertility. Quality of life is increasingly important to long-term survivors of cancer, and one of the major quality-of-life issues is the ability to produce and raise normal children. Developments in the near future in the emerging field of fertility preservation in cancer survivors promise to be very exciting. This article reviews the published literature, discusses the effects of cancer treatment on fertility and presents the options available today thanks to advances in assisted-reproduction technology for maintaining fertility in male and female patients undergoing this type of treatment. The various diagnostic methods of assessing the fertility potential and the efficacy of in vitro fertilization (IVF) after cancer treatment are also presented.

Adult↗

Hormonal actions during oocyte maturation influence fertilization and early embryonic development.

On the basis of evidence just reviewed, the hormonal requirements during IVM of mammalian oocytes for fertilization and developmental competence may be summarized as follows: 1. Nuclear maturation occurs "spontaneously," without follicular factors or hormones, in all mammalian species. 2. Cumulus cells are necessary during nuclear maturation in culture for fertilization and developmental competence. Their effect is enhanced by the addition of serum or follicular fluid to the maturation medium. 3. FSH retards nuclear maturation, perhaps thereby enhancing subsequent developmental competence by allowing more time for cytoplasmic maturation to occur before fertilization. The effects of FSH are mediated, in part, by soluble factors from cumulus or granulosa cells. 4. FSH in vivo before culture or added in vitro to IVM culture media enhances fertilization and stimulates steroidogenesis (progesterone and estradiol) in cumulus cells. Blockade of steroidogenesis prevents the enhancing effect of FSH on fertilization. Progesterone can substitute for FSH in enhancing fertilization of rat oocytes. 5. Other hormones enhance beneficial effects of FSH, with some apparent species differences: a. Rat: Progesterone may mediate the FSH effect. b. Cow, rabbit: Estradiol enhances the beneficial effect of FSH. c. Rabbit: Prolactin further enhances the effects of estradiol and FSH. d. Human: No evidence is available on the possible synergism between steroids and gonadotropins in enhancing in vitro maturation. It is clear that further research is required to elucidate the mechanisms of action of all the hormones that have been observed to influence oocyte maturation, and to establish the physiologic significance of most of these, particularly in species other than laboratory rodents. Major benefits to animal production and human health are likely to accrue from such research.

Animals↗

The effects of lactation on the fertility of dairy cows.

Lactation has been negatively associated with fertility because pregnancy rates in maiden heifers exceed those obtained after first or subsequent calvings. The extent of this difference is less in pasture-fed dairy cows ( < 10%) than in American Holsteins ( > 20%) fed grain and conserved forages. The latter cows have pregnancy rates to first insemination and oestrus detection rates of only 40 to 45%. This suggests that the subsequent fertility of inherently fertile Holstein heifers may be severely compromised by high levels of milk production. International comparisons show that pasture-fed dairy cows may experience extended periods of anovulatory anoestrum but have normal fertility (60% pregnancy rate to first insemination) once cycling. The high-producing American Holstein may ovulate within 4 weeks postpartum but is more likely to continue ovulating without being detected in oestrus. Both situations are associated with negative energy balances (NEB) during early lactation. The severity and duration of this NEB may vary with body condition at calving, age or parity, ration formulation, production level and environmental factors. Relative daily milk yield is not an absolute indicator of NEB, because some lower producing cows within a herd have lower feed intakes and more severe energy deficits. NEB is not simple to measure; nonetheless, it is correlated with genetic improvement for milk yield. A positive energy balance, greater weight gain and higher body condition score have all been shown to be positively correlated with plasma progesterone concentrations in early lactation. No studies have investigated the possibility that the rapid increase in metabolic rate at this time may also alter steroid concentrations with consequent effects on oestrous behaviour and fertility. Studies to more precisely define the effects of increasing milk yields in early lactation, especially in Holsteins, may need to be completed in Australia and New Zealand. Oestrus detection rates and pregnancy rates for American Holsteins of less than 50% are accepted widely in the USA. Such low detection rates confound studies on fertility. The objective should be to increase these 2 rates to at least 80% and 60% respectively. This may involve the use of controlled breeding, especially if oestrous behaviour is less overt in high-producing Holstein cows.

Animals↗

Fertilization-related sperm antigens and their immunocontraceptive potentials.

Vaccine(s) for contraception will provide an attractive alternative to contraception. There has been a renewed interest in defining fertilization-related sperm antigens that can be used for the development of a contraceptive vaccine. The sperm-zona pellucida (ZP) recognition and binding constitutes the most important event in the fertilization process, and the molecules involved at this site are attractive candidates for immunocontraception. Extensive research indicates that there are four sperm surface proteins that bind to oocyte ZP3 in humans and they belong to the four molecular regions of 95, 63, 51, and 14-18 kDa, respectively. Our laboratory is actively engaged in cloning and sequencing of cDNAs encoding for these sperm proteins and investigating the applications of recombinant (r) proteins in immunocontraception and infertility. Presently, the cDNAs encoding for the 14-18-kDa proteins, designated the NZ-1 and NZ-2, respectively, and the 51-kDa protein, designated fertilization antigen, have been cloned and sequenced. Active immunization with the rFA-1 antigen caused a reversible block/inhibition in fertility of female mice by raising a sperm/testis-specific immune response. FA-1 antigen is also involved in human immunoinfertility, and a recent clinical trial indicates that it will have a clinical application in the treatment of immunoinfertile men. The long-term goal is to employ various recombinant fertilization antigens and/or their bioeffective peptide epitopes in a single formulation, to generate an anti-sperm vaccine that will be strongly immunogenic and highly efficacious for regulation of fertility.

Animals↗

Voltage-clamp study of the conductance activated at fertilization in the starfish egg.

Ionic currents underlying the fertilization potential of the egg of the starfish Mediaster aequalis were studied using a two-micro-electrode voltage clamp. Mature eggs were fertilized in vitro under voltage-clamp conditions. The fertilization current, here termed IF, was induced by adding sperm to sea water bathing the egg. At a holding potential of -70 mV, IF was inward. It reached a peak within 2-4 min and then decayed over the next approximately 20 min with a rate which depended on the holding membrane potential. Instantaneous current-voltage relations measured at different times during IF were approximately linear and reversed at a potential of +6.0 +/- 5.8 mV (mean +/- S.D., n = 11). Membrane chord conductance was highest at the peak of inward current and the declining phase of IF was due to a decrease in conductance towards the pre-fertilization level. When the membrane potential was rapidly stepped to levels more positive than about -45 mV, the conductance underlying IF decreased in a manner which depended on both membrane potential and time. The fertilization-specific conductance showed a sigmoidal activation curve between -50 and +10 mV with a half-activation level of -25 mV. Analysis of the steady-state voltage dependence indicated that at the peak of the fertilization potential (+10 to +15 mV) only 4-5% of the total available channels would be open. Current relaxations followed first-order kinetics and the relaxation time constant depended upon the membrane potential during the voltage pulse. The relation between the time constant and voltage was bell-shaped, decreasing at potentials more negative than -40 and more positive than 0 mV. Both the steady-state conductance-voltage relation and the kinetics of the current relaxations were consistent with a simple two-state gating model in which the probability of a channel being open is determined by a single gating particle with an effective valency of -1.7 moving through the entire membrane field. The shifts in reversal potential with changes in external Na (at 10 mM-external K) were analysed using the constant field expression, which gave a relative permeability of Na to K of approximately 0.6.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Fertility in the United States.

From the postwar high of 3.8 births per woman at the peak of the baby boom, the total fertility rate in the United States has fallen to 1.8, where it has remained unchanged for nearly a decade. This below-replacement level of fertility has, in recent decades, characterized most Western countries, some of which have shown declines to well below 1.5 births per woman. Were it not for the continued infusion of immigrants, the U.S. population, which already shows the aging characteristic of low fertility, would stop growing and begin to decline before the middle of the next century. The low fertility in the United States has been accomplished by a postponement of marriage and by the widespread use of contraception, with heavy reliance on surgical sterilization as a contraceptive method. Judging from the experience of other Western countries and from our own historical experience of two centuries of fertility decline interrupted only by the baby boom, as well as from the absence of social trends that would counteract those contributing to that decline, the prognosis is for a continued low level of fertility in the United States.

Adolescent↗

Use of molecular and isotopic techniques to monitor the response of autotrophic ammonia-oxidizing populations of the beta subdivision of the class proteobacteria in arable soils to nitrogen fertilizer.

This study examined the effects of NH(4)NO(3) fertilizer on the size and activity of nitrifying, autotrophic, ammonia-oxidizing populations of the beta subdivision of the class Proteobacteria in arable soils. Plots under different long-term fertilizer regimes were sampled before and after NH(4)NO(3) additions, and the rates of nitrification were determined by (15)N isotopic pool dilution assays. Ammonia-oxidizing populations in the plots were quantified by competitive PCR assays based on the amoA and ribosomal 16S genes. Prior to fertilizer addition, ammonium concentrations and nitrification rates in the plots were comparatively low; ammonia-oxidizing populations were present at 10(4) to 10(5) gene copies g of soil(-1). Three days after the application of fertilizer, nitrification rates had risen considerably but the size of the ammonia-oxidizing population was unchanged. Six weeks after fertilizer treatment, ammonium concentrations and nitrification rates had fallen while the ammonia-oxidizing populations in plots receiving fertilizer had increased. The rapidity of the rise in nitrification rates observed after 3 days suggests that it results from phenotypic changes in the ammonia-oxidizing bacterial population. Associated increases in population sizes were only observed after 6 weeks and did not correlate directly with nitrifying activity. Phylogenetic analyses of PCR products from one of the plots revealed a population dominated by Nitrosospira-type organisms, similar to those prevalent in other soils.

Betaproteobacteria↗

Precontact mammalian sperm-egg communication and role in fertilization.

In creatures with external fertilization, e.g., metazoa, it is well established that there is precontact sperm-egg communication in the form of chemotaxis. An intriguing question is whether also in mammals, where fertilization is internal and the need for precontact sperm-egg communication is not self-evident, such a process occurs and what its physiological significance may be. Here we review the evidence related to such a process in mammals, evidence which suggests that sperm attraction to the ovulated egg may indeed occur. On the basis of the available data we propose a hypothesis, according to which a sperm population is heterogeneous with respect to its physiological state; some spermatozoa are at a physiological state ready for fertilizing an egg, while others are premature or overmature. According to the hypothesis this is a dynamic state; the population of fertilizing spermatozoa gradually loses its potency and, at the same time, other spermatozoa mature and acquire fertilizing ability. After ovulation, only the fertilizing spermatozoa are attracted to the egg, while the rest are either repelled or inhibited and thus prevented from reaching the egg. The potential significance of sperm-egg communication is discussed.

Animals↗

Calcium at fertilization and in early development.

Fertilization calcium waves are introduced, and the evidence from which we can infer general mechanisms of these waves is presented. The two main classes of hypotheses put forward to explain the generation of the fertilization calcium wave are set out, and it is concluded that initiation of the fertilization calcium wave can be most generally explained in invertebrates by a mechanism in which an activating substance enters the egg from the sperm on sperm-egg fusion, activating the egg by stimulating phospholipase C activation through a src family kinase pathway and in mammals by the diffusion of a sperm-specific phospholipase C from sperm to egg on sperm-egg fusion. The fertilization calcium wave is then set into the context of cell cycle control, and the mechanism of repetitive calcium spiking in mammalian eggs is investigated. Evidence that calcium signals control cell division in early embryos is reviewed, and it is concluded that calcium signals are essential at all three stages of cell division in early embryos. Evidence that phosphoinositide signaling pathways control the resumption of meiosis during oocyte maturation is considered. It is concluded on balance that the evidence points to a need for phosphoinositide/calcium signaling during resumption of meiosis. Changes to the calcium signaling machinery occur during meiosis to enable the production of a calcium wave in the mature oocyte when it is fertilized; evidence that the shape and structure of the endoplasmic reticulum alters dynamically during maturation and after fertilization is reviewed, and the link between ER dynamics and the cytoskeleton is discussed. There is evidence that calcium signaling plays a key part in the development of patterning in early embryos. Morphogenesis in ascidian, frog, and zebrafish embryos is briefly described to provide the developmental context in which calcium signals act. Intracellular calcium waves that may play a role in axis formation in ascidian are discussed. Evidence that the Wingless/calcium signaling pathway is a strong ventralizing signal in Xenopus, mediated by phosphoinositide signaling, is adumbrated. The central role that calcium channels play in morphogenetic movements during gastrulation and in ectodermal and mesodermal gene expression during late gastrulation is demonstrated. Experiments in zebrafish provide a strong indication that calcium signals are essential for pattern formation and organogenesis.

Animals↗

Correlation between progesterone binding sites on human spermatozoa and in vitro fertilization outcome.

We investigated whether the expression of progesterone-binding sites on human sperm acrozomal membrane is correlated with in vitro fertilization outcome. In motile sperm we evaluated percentage of progesterone-binding sperm (%PB) and of acrozome-reacted sperm (%AR), collected from 39 male partners undergoing an in vitro fertilization program (IVF), by labeling the sperm with progesterone-conjugated BSA-labeled FITC (P-BSA-FITC) and pisum sativum agglutinin labeled-FITC (PSA-FITC). Mean %PB in 30 fertilized cases was significantly higher than that in 9 fertilization failures (9.0 +/- 5.1 vs. 22.3 +/- 14.8%, p < 0.01). Furthermore, %PB shows a strong positive correlation with fertilization rate in IVF (r = 0.44) and %AR (r = 0.62), but not with sperm concentration and sperm motility. These results suggest that the expression of progesterone receptor on the sperm was related to the sperm fertilizability, and the evaluation of %PB was useful for predicting the fertilization outcome of IVF.

Cell Membrane↗

Fertility, sex determination, and the X chromosome.

Because of its function, the X chromosome has a special status in mammalian genomes, with the specific occurrence of genes that influence both female and male fertility. Long ago, the XO karyotype (Turner syndrome) was associated with infertility, proving the correlation between normal X chromosome dosage and normal female fertility. Nevertheless, the search for specific X-borne fertility genes was not completely successful and suggested, instead, that female X-linked fertility, for example, depends upon groups of X-linked genes. Conversely, X-linked hyperfertility has been observed in sheep, where a mutation in BMP15 leads to a hyperfertile phenotype, but only in the heterozygous state. Many male fertility genes map to the X chromosome, consistent with a genetic model developed in the early 1990s. Ironically, NR0B1 (formerly DAX1), once presented as the paradigm of genes responsible for ovarian development and function, is probably one of these male fertility factors and is active in the maintenance of spermatogenesis. Indeed, duplications of this gene on the human X chromosome lead to XY sex reversal, as NR0B1 is able to counterbalance the effect in humans. Nevertheless, invalidation experiments in mice demonstrate the effect of this factor on male germ-cell production.

Animals↗

Present and future options for the preservation of fertility in female adolescents with cancer.

Fertility and sexuality are important aspects in the quality of life of long-term survivors of cancer. Adolescents in particular are in a very vulnerable period of their lives with respect to future fertility and sexuality. Special attention should be paid to preserve their fertility whenever possible. The gonadotoxic effect of chemotherapy is largely drug- and dosedependent and is related to age. The effect of radiotherapy is also dependent on dose and age and on the radiation therapy field. The prepubertal ovary is the least susceptible to gonadotoxicity. Ablative regimens for stem cell transplantation have an extremely high risk of ovarian failure. Alternative chemotherapy protocols can reduce long-term gonadotoxicity. Alkylating agents impose the highest risk in causing ovarian failure and should be avoided whenever possible. Up to now, the results of gonadoprotective hormonal therapy have been disappointing and contradictory. Transposition of the ovaries should be considered in each case of planned pelvic or whole body irradiation, where ovarian involvement is unlikely and chemotherapy not necessary. Cryopreservation of preimplantation embryos will seldom be possible in female adolescents due to the lack of a stable relationship with a male partner. Cryopreservation of mature and immature oocytes (necessitating in vitro maturation) is still assumed not to be safe for the offspring. Cryopreservation and transplantation of ovarian tissue seems to be the most promising way of future fertility preservation in female adolescents. At present, it is in its early experimental stage. Its safety and possibilities for fertility preservation in humans are not proven as yet. Additionally, technical and ethical issues need to be addressed. The counseling of female adolescents who are facing the threat of cancer needs careful consideration with regards to the psychosocial impact of the treatment and its consequences. Special attention should be paid to aspects of future quality of life, in particular: fertility and sexuality.

Adolescent↗

Antiidiotypic antibodies to sperm in sera of fertile women that neutralize antisperm antibodies.

The presence of antiidiotypic antibodies (ab-2) to sperm was investigated in the sera of fertile, infertile, and virgin women using sperm-specific anti-FA-1 monoclonal antibody Fab'.ab-2 were detected in 71% (17/24) of sera from fertile women and in none (0/12) of the sera from virgin females by the enzyme-linked immunosorbent assay, Western blot procedure, and immunoprecipitation procedure. Sera from infertile women that had antisperm antibodies showed a minimal presence of ab-2, with only three sera (13%, 3/23) demonstrating the presence of low levels of ab-2. The ab-2 present in fertile women were capable of neutralizing the fertilization-inhibitory activity of anti-FA-1 antibody in a concentration-dependent manner in a human sperm penetration assay (SPA) of zona-free hamster oocytes. ab-2 were also capable of inhibiting the binding of antisperm antibodies to the sperm surface as determined by the immunobead binding technique. This is the first report demonstrating the presence of ab-2 in the sera of fertile women that are capable of neutralizing antisperm antibodies present in sera of infertile women. These findings suggest that the inability to detect antisperm antibody activity in the sera of fertile women may be due to higher levels of ab-2 present in these sera than levels found in sera of infertile women, although both groups may be producing antisperm antibody response after sexual exposure to sperm.

Adult↗

Calcium dynamics during fertilization in C. elegans.

BACKGROUND: Of the animals typically used to study fertilization-induced calcium dynamics, none is as accessible to genetics and molecular biology as the model organism Caenorhabditis elegans. Motivated by the experimental possibilities inherent in using such a well-established model organism, we have characterized fertilization-induced calcium dynamics in C. elegans. RESULTS: Owing to the transparency of the nematode, we have been able to study the calcium signal in C. elegans fertilization in vivo by monitoring the fluorescence of calcium indicator dyes that we introduce into the cytosol of oocytes. In C. elegans, fertilization induces a single calcium transient that is initiated soon after oocyte entry into the spermatheca, the compartment that contains sperm. Therefore, it is likely that the calcium transient is initiated by contact with sperm. This calcium elevation spreads throughout the oocyte, and decays monotonically after which the cytosolic calcium concentration returns to that preceding fertilization. Only this single calcium transient is observed. CONCLUSION: Development of a technique to study fertilization induced calcium transients opens several experimental possibilities, e.g., identification of the signaling events intervening sperm binding and calcium elevation, identifying the possible roles of the calcium elevation such as the completion of meiosis, the formation of the eggshell, and the establishing of the embryo's axis of symmetry.

Animals↗

Biochemical heterogeneity, migration, and pre-fertilization release of mouse oocyte cortical granules.

BACKGROUND: Oocyte cortical granules are important in the fertilization of numerous species including mammals. Relatively little is known about the composition, migration, and pre-fertilization release of mammalian oocyte cortical granules. RESULTS: Results obtained with confocal scanning laser microscopy indicated that mouse oocytes have at least two populations of cortical granules, one that bound both the lectin LCA and the antibody ABL2 and one that bound only LCA. Both types of granules were synthesized at the same time during oocyte maturation suggesting that the ABL2 antigen is targeted to specific granules by a sorting sequence. The distribution of both populations of cortical granules was then studied during the germinal vesicle to metaphase II transition. As the oocytes entered metaphase I, the first cortical granule free domain, which was devoid of both populations of cortical granules, formed over the spindle. During first polar body extrusion, a subpopulation of LCA-binding granules became concentrated in the cleavage furrow and underwent exocytosis prior to fertilization. Granules that bound ABL2 were not exocytosed at this time. Much of the LCA-binding exudate from the release at the cleavage furrow was retained in the perivitelline space near the region of exocytosis and was deduced to contain at least three polypeptides with approximate molecular weights of 90, 62, and 56 kDa. A second cortical granule free domain developed following pre-fertilization exocytosis and subsequently continued to increase in area as both, LCA and LCA/ ABL2-binding granules near the spindle became redistributed toward the equator of the oocyte. The pre-fertilization release of cortical granules did not affect binding of sperm to the overlying zona pellucida. CONCLUSIONS: Our data show that mouse oocytes contain at least two populations of cortical granules and that a subset of LCA-binding cortical granules is released at a specific time (during extrusion of the first polar body) and place (around the cleavage furrow) prior to fertilization. The observations indicate that the functions of the cortical granules are more complex than previously realized and include events occurring prior to gamete membrane fusion.

Animals↗

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