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PubMedDate not supplied

[Our experience with the programmable Codman-Medos valve: review of 125 shunts].

INTRODUCTION: Programmable valves are a possible solution in cases of excessive or insufficient draining. OBJECTIVE: To report our experience with these shunts and clarify concepts. PATIENTS AND METHODS: We have implanted 125 Codman-Medos programmable devices in 118 patients. The most frequent indication was secondary hydrocephalus, particularly due to obstruction by a tumour, and primary hydrocephalus. They were also used in cases of benign intracranial hypertension, CSF fistulas and arachnoid cysts. Most valves were inserted frontally, under antibiotic prophylaxis. RESULTS: Excluding patients with a follow-up of less than three months, the average follow-up was 14.63 +/- 9.07 months, with clinical improvement in 80%. There was 0% mortality in relation to surgery. The initial average pressure was 121.84 +/- 24.74 mmH2O and after 52 reprogrammings done in 36 (30%) of the patients, the final average pressure was 124.96 +/- 30.58 mmH2O. Reprogramming was done for the management of symptoms and to avoid subdural hygromas. We have observed no clinical signs of unprogramming. There were 29 complications which were treated by reprogramming in 7 cases and surgically in the remainder. CONCLUSIONS: We recommend frontal insertion, with a long peritoneal catheter, mainly in patients with hydrocephalus secondary to stenosis of the aqueduct of Sylvius, benign intracranial hypertension, after head injury and Arnold-Chiari malformation. The initial pressure is difficult to determine but tends to be average or high. Reprogramming is particularly useful in the treatment of subdural hygromas. We have observed no clinical signs of unprogramming. Complications tend to be due to surgical technique rather than the particular shunt used.

Adolescent↗

PubMedDate not supplied

[Effect of age of cell donors of nuclei on effectivness of developing cloned rabbit embryos].

We studied the capacity of nuclei of rabbit fibroblasts taken from various developmental stages for reprogramming in the cytoplasm of mature aging enucleated oocytes and development of the cloned embryos to the preimplantation stages. A negative correlation was found between the age of an animal--donor of fibroblasts and efficiency of the development of cloned embryos (rmorula-blastocyst = -0.826, rblastocyst = -0.7139). A reliably decreased capacity for reprogramming of the nuclei of donor fibroblasts was shown upon transition from prenatal development to the postnatal one, as well as a trend to a decreased capacity of nuclei for reprogramming during aging. Aging of cells in the culture, at least until the 10th passage, did not affect the capacity of the nuclei of fetal fibroblasts for reprogramming and development of cloned embryos.

Age Factors↗

PubMed1990

Cloning of embryos.

Nuclear transfer for the study of differentiation in amphibians has been used since the 1950s, but not until recently have the same procedures been applied successfully to some mammals. Nuclear transfer, as developed for the amphibian, is successful in sheep, cattle, rabbit, and pig, but not mouse embryos. This fact is discussed in relation to the species-specific timing of the activation of the zygotic genome. Nuclear transfer to an oocyte presumably results in a genomic reprogramming of the transferred nucleus. The limits of differentiation that can be reprogrammed have yet to be determined. Since the cells of early embryos are thought to have identical nuclear genomes, early embryos can be used as a source of donor nuclei; and, when combined with serial nuclear transfer, can theoretically produce an unlimited number of identical offspring. Cloning by splitting does not result in a reprogramming of the genome and is limited in the number of identical offspring that can result. Here we discuss some of the factors to consider concerning micromanipulation and nuclear reprogramming and how they relate to other embryo technologies.

Animals↗

PubMed2025

Fetal-like reversion in the regenerating intestine is regulated by mesenchymal asporin.

Mesenchymal cells and the extracellular matrix (ECM) support epithelium during homeostasis and regeneration. However, the role of the mesenchyme in epithelial conversion into a fetal-like regenerative state after damage is not known. We modeled epithelial regeneration by culturing intestinal epithelium on decellularized small intestinal scaffolds (iECM) and identify asporin (Aspn), an ECM-bound proteoglycan, as a critical mediator of epithelial fetal-like reprogramming. After damage, transient increase in Aspn expression by the pericryptal fibroblasts induces epithelial transforming growth factor β (TGF-β)-signaling via CD44 and promotes timely epithelial reprogramming. Temporal control of Aspn is lost in old mice, and after damage, the persistently high level of Aspn stagnates epithelium in the regenerative state. Increase in Wnt signaling can resolve the stagnated regenerative program of the old epithelium, promoting restoration of tissue function. In summary, we establish a platform for modeling epithelial injury responses ex vivo and show that the mesenchymal Aspn-producing niche modulates tissue repair by regulating epithelial fetal-like reprogramming.

Animals↗

PubMed2026

Transcription regulation of cell fate plasticity - from embryonic development to tissue regeneration.

Cell fate plasticity refers to the capacity of cells sharing the same genome to alter, reverse, or reconfigure their identity under physiological, pathological, or experimental conditions. This property underlies embryonic development, cellular reprogramming, and tissue regeneration, but becomes progressively restricted as lineage identity is stabilized. Embryonic development represents an intrinsic process of fate transitions, whereas reprogramming and regeneration reveal how differentiated cells can dedifferentiate or transdifferentiate under specific conditions. Across these contexts, plasticity is governed by multilayered regulatory networks involving transcription factors, epigenetic regulators, cofactors, and the core transcription machinery. Robust regulatory programs stabilize cell identity, whereas stochastic fluctuations in gene expression and chromatin state can prime cells for fate transitions, adding a tunable dimension to plasticity control. In this review, we synthesize recent advances in the regulation of cell fate plasticity across development, reprogramming, and regeneration, highlighting how transcription factors, epigenetic modifications, transcriptional cofactors, and core transcription machinery cooperate to control cell fate decisions and plasticity.

Animals↗

PubMed2026

Crosstalk between S-nitrosylation and glycation defines a metabolic vulnerability in liver and renal cancers.

Metabolic reprogramming is a defining feature of cancer; however, how it contributes to therapeutic resistance remains incompletely understood. Here we show that loss of aldo-ketoreductase 1A1 (AKR1A1) in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) disrupts terminal glycolytic flux and lactate production through S-nitrosylation-mediated inhibition of pyruvate kinase, resulting in the accumulation of methylglyoxal (MGO). In multiple AKR1A1-deficient models, but not in those endogenously expressing the C423/424 A mutant of pyruvate kinase M2, elevated MGO triggers autophagic degradation of Kelch-like ECH-associated protein 1, leading to Nuclear factor erythroid 2-Related Factor 2 (NRF2) activation and transcriptional reprogramming. This NRF2-driven response enhances chemoresistance and promotes tumor cell migration, two hallmarks of aggressive cancer. Therapeutically, we demonstrate that pharmacological inhibition of the glyoxalase system-the major pathway for MGO detoxification-restores drug sensitivity in patient-derived cells and xenograft models, revealing a context-dependent metabolic vulnerability in AKR1A1 loss conditions. These findings identify AKR1A1 as a metabolic tumor suppressor and uncover crosstalk between S-nitrosylation and glycation as a key regulatory axis linking metabolic reprogramming to NRF2-driven therapy resistance, offering glyoxalase inhibition as a potential precision treatment strategy for RCC and HCC.

Humans↗

PubMed2019

Profiling the long noncoding RNA interaction network in the regulatory elements of target genes by chromatin in situ reverse transcription sequencing.

Long noncoding RNAs (lncRNAs) can regulate the activity of target genes by participating in the organization of chromatin architecture. We have devised a "chromatin-RNA in situ reverse transcription sequencing" (CRIST-seq) approach to profile the lncRNA interaction network in gene regulatory elements by combining the simplicity of RNA biotin labeling with the specificity of the CRISPR/Cas9 system. Using gene-specific gRNAs, we describe a pluripotency-specific lncRNA interacting network in the promoters of Sox2 and Pou5f1, two critical stem cell factors that are required for the maintenance of pluripotency. The promoter-interacting lncRNAs were specifically activated during reprogramming into pluripotency. Knockdown of these lncRNAs caused the stem cells to exit from pluripotency. In contrast, overexpression of the pluripotency-associated lncRNA activated the promoters of core stem cell factor genes and enhanced fibroblast reprogramming into pluripotency. These CRIST-seq data suggest that the Sox2 and Pou5f1 promoters are organized within a unique lncRNA interaction network that determines the fate of pluripotency during reprogramming. This CRIST approach may be broadly used to map lncRNA interaction networks at target loci across the genome.

Animals↗

PubMed2005

Management of referred deep brain stimulation failures: a retrospective analysis from 2 movement disorders centers.

BACKGROUND: Since the Food and Drug Administration approved DBS, there has been a surge in the number of centers providing the procedure. There is currently no consensus regarding appropriate screening procedures, necessary training of individuals providing the therapy, the need for an interdisciplinary team, or guidelines for the management of complications. An increasing number of patients come to experienced DBS centers after unsatisfactory results from DBS surgery. An attempt is made herein to evaluate the reasons for DBS failure in a series of such patients and to make recommendations to improve overall DBS outcomes. OBJECTIVE: To improve outcomes of deep brain stimulation (DBS) surgery by analyzing a series of patients who had suboptimal results from DBS. METHODS: Forty-one consecutive patients complaining of suboptimal results from DBS surgery came to the University of Florida Movement Disorders Center, or to Beth Israel Movement Disorders Center, over a 24-month period. All patients had undergone implantation of DBS devices at outside medical centers. Each patient was evaluated by a movement disorders neurologist, and the complete medical record was reviewed. The DBS device for each patient was interrogated for adverse effects and programmed for maximal benefit. Postoperative imaging studies were evaluated whenever possible. RESULTS: The average age of patients was 63.4 years (range, 49-84 years). The indication for surgery (by record review) included 9 patients with essential tremor, 31 with Parkinson disease, and 1 with dystonia. The diagnoses after referral examination included 5 with essential tremor, 26 with Parkinson disease, 3 with Parkinson disease and dementia, 1 with Parkinson disease and essential tremor, 1 with corticobasal degeneration, 1 with dystonia, 2 with multiple system atrophy, 1 with progressive supranuclear palsy, and 1 with myoclonus. Issues related to inadequate preoperative screening: Thirty (73%) of 41 patients saw a movement disorders specialist prior to DBS implantation. Fourteen (34%) patients had neuropsychological testing, 4 (10%) did not have testing, and in 23 cases (56%), it could not be determined whether or not they were tested. Five (12%) of 41 patients had an inadequate medication trial, and 5 patients (12%) had significant cognitive dysfunction prior to their DBS implantation. Surgical and device-related complications: Nineteen (46%) of 41 patients had suboptimally placed electrodes. Seven electrodes (17%) were replaced with improvement. Three patients' devices had failed due to end of battery life, 2 had infections, and 1 had a fractured lead. Programming and medication adjustments: Seven (17%) of 41 patients had no or poor access to programming. Two patients (5%) moved, and 2 physicians (5%) moved, creating issues with access to care. Eight patients (20%) required local follow-up (they flew to remote centers to have the surgery performed). Fifteen patients (37%) were inadequately programmed and improved significantly with reprogramming. Six patients (15%) experienced partial improvement with reprogramming, and 21 patients (51%) failed to improve despite extensive reprogramming. Thirty patients (73%) benefited from medication changes, 4 (10%) had antidepressants added to their regimens, and 1 (2%) had donepezil hydrochloride added. One patient's carbidopa/levodopa (2%) was restarted after complete discontinuation. OUTCOMES: With the various postoperative interventions described, 21 (51%) of 41 patients had good outcomes, 6 (15%) had modest clinical improvement, and 14 (34%) did not improve. CONCLUSIONS: With appropriate intervention, 51% of patients who complained of "failed" DBS procedures ultimately had good outcomes. Thirty-four percent of these patients had persistently poor outcomes despite maximal intervention. This case series provides important insights into reasons for "DBS failure" and proposes strategies to manage patients with DBS more effectively.

Aged↗

PubMed1996

Influence of recipient cytoplasm cell stage on transcription in bovine nucleus transfer embryos.

Nucleus transfer for the production of multiple embryos derived from a donor embryo relies upon the reprogramming of the donor nucleus so that it behaves similar to a zygotic nucleus. One indication of nucleus reprogramming is the RNA synthetic activity. In normal bovine embryogenesis, the embryo relies upon maternally derived RNA transcripts up to the 8-cell stage, at which time it begins to transcribe its own RNA. In this experiment, RNA synthesis was detected in nucleus transfer embryos (NTE) and control embryos by pulsing with 3H-uridine, fixation, and autoradiography on semithin sections. NTE were produced using either a MII phase (nonactivated) cytoplasts at 32 hr of maturation or S-phase (activated) cytoplasts activated with calcium ionophore A23187 and cycloheximide treatment approximately 8 hr prior to fusion with a blastomere from an in-vitro-produced morula stage embryo at 32 hr of maturation. Control in-vitro-produced embryos were 3H-uridine-labelled and fixed at the 2-, 4-, early 8-, and late 8-cell stages. NTE were similarly prepared at 1, 3, and 20 hr postfusion and at the 2-, 4-, and 8-cell stages. In the control embryos, RNA synthesis was absent in the 2-, 4-, and early 8-cell stages, whereas in all late 8-cell stages, it was present. In NTE from nonactivated (MII phase) cytoplasts, there was a sharp decline in RNA synthesis at 1 hr and 3 hr after fusion and a total absence by 20 hr after fusion. In contrast, NTE from activated (S phase) cytoplasts exhibited continued high levels of RNA synthesis at 1 hr and moderate levels at 3 hr after fusion, although it had ceased by 20 hr after fusion. In all NTE (activated and nonactivated cytoplasts), there was no RNA synthesis seen at the 2-cell stage. However, at the 4-cell stage, weak RNA synthesis was seen in all NTE from activated cytoplasts, whereas none was observed in those from MII nonactivated cytoplasts. At the 8-cell stage, nearly all NTE from S-phase cytoplasts showed weak to moderate levels of RNA synthesis. We conclude that the nucleus reprogramming differs between NTE reconstructed from activated and nonactivated cytoplast with the former undergoing a slower cessation of RNA synthesis after fusion and earlier resumption of RNA synthesis, occurring as early as the 4-cell stage.

Animals↗

PubMed2005

Cloned pre-implantation mouse embryos show correct timing but altered levels of gene expression.

Mammalian embryos obtained by somatic nuclear transfer (NT) struggle to survive throughout development, encountering a number of hurdles leading to wrong functional reprogramming of the donor genome. However, despite these obstacles, some of these embryos continue their development, as if the required transcriptional functions are somehow satisfied. The amount of information gathered on the kinetics and quantitative profile of gene expression in NT pre-implantation embryos is still scarce and limited to a handful of genes described in two species, bovine and mouse. Using a single-cell sensitive semi-quantitative RT-PCR, we have compared the onset and profile of abundance of Hprt, Tsx, Bex1, Bax, Cpt2, and Oct4 genes, in in vitro fertilised and NT-derived mouse 1-cell, 2-cell, 4-cell embryos, morulae, and blastocysts. The genes analysed were activated in NT embryos at approximately the correct time compared to control embryos, indicating that the reprogramming phenomenon is developmentally regulated and that the somatic genome is quickly rearranged towards an embryonic-type of expression during the early stages of segmentation. Despite the right timing of genes onset, the high degree of variability in the number of transcripts found in NT embryos at the latest stages of pre-implantation development, suggests that genome reprogramming is incomplete and inaccurate.

Animals↗

PubMed2005

Knockdown of the Dnmt1s transcript using small interfering RNA in primary murine and bovine fibroblast cells.

RNA interference (RNAi) has rapidly developed into one of the most widely applied technologies in molecular and cellular research, and although young, is now an essential experimental tool. The versatility of RNAi, especially in mammalian species, lends to its potential applications in a wide array of fields. Without having to genetically manipulate the genome, the ability to selectively reduce the level of a specific transcript using small interfering RNA (siRNA) molecules has great appeal in studying reprogramming issues in somatic cell nuclear transfer (SCNT) embryos. In such embryos, the aberrant expression of the somatic isoform of Dnmt1 (Dnmt1s), the enzyme responsible for maintaining DNA methylation in all somatic cells, has been implicated as one factor in the improper reprogramming of the donor genome. In the present study, the ability to develop a method allowing for the knockdown, or reduction, of Dnmt1s in primary fibroblast cells, like those commonly used as karyoplast donors in SCNT studies, was investigated in primary murine and bovine fibroblast cells as well as in a compromised cell line (NIH/3T3). Two Dnmt1s-specific siRNA candidates were designed and tested. Using optimized conditions, these siRNAs were transiently transfected into the cells with total RNA and nuclear protein being collected. A 56.5% knockdown in Dnmt1s was achieved in the compromised and primary murine cells whereas Dnmt1s was reduced by 15.4% in the primary bovine cells. A reduction in Dnmt1s mRNA did not correspond to a reduction in protein as determined by immunodetection of Western blots. Overall, this study demonstrated the ability of siRNA to knockdown Dnmt1s mRNA in primary fibroblast donor cells. In order to substantially increase the efficiency while decreasing the anomalies seen in SCNT, novel techniques, like the one proposed, are needed to assist the oocyte's ability to reprogram a differentiated genome.

Animals↗

PubMed2006

Gradual DNA demethylation of the Oct4 promoter in cloned mouse embryos.

During differentiation, somatic cell nuclei acquire unique patterns of epigenetic modifications, such as DNA methylation, which affect the transcriptional activity of specific genes. Upon transfer into oocytes, however, the somatic nucleus undergoes reprogramming of these epigenetic modifications to achieve pluripotency. Oct4 is one of the critical pluripotency regulators, and is expressed in the germ line, including the pluripotent early embryonic cells. Previous studies showed that the upstream regulatory sequences of the Oct4 gene are distinctly methylated in somatic cells, and the DNA methylation of the regulatory sequences suppresses the transcriptional activity. Thus, successful reprogramming of the somatic cell nucleus to gain pluripotency must be accompanied by the demethylation of the Oct4 regulatory sequences. Here, we investigated the methylation pattern of the Oct4 promoter during early development of cloned mouse embryos. We found that the Oct4 promoter was only gradually demethylated during the early cleavage stages and that the ineffective demethylation of the promoter was associated with developmental retardation. We also found that the upstream sequences of the other pluripotency regulators, namely Nanog, Sox2, and Foxd3, were considerably under-methylated in cumulus cells. These results suggest that the Oct4 gene, as compared to the other pluripotency regulators, needs to undergo extensive demethylation during nuclear reprogramming, and that the failure of such demethylation is associated with inefficient development of cloned somatic cell embryos.

Animals↗

PubMed1996

Specific developmental changes in the regulatory subunits of the 26 S proteasome in intersegmental muscles preceding eclosion in Manduca sexta.

Previously, we have shown extensive reprogramming of the ATPase regulator of the 26S proteasome preceding the programmed destruction of intersegmental muscles (ISM) in the tabacco horn moth Manduca sexta (Dawson et al., J. Biol. Chem, 270, 1850-1858, 1995). We now show that the extensive reprogramming of the regulatory components of the 26S proteasome occurs only in ISM and not in flight muscles (FM), which undergo terminal differentiation at ecdysis. Unlike in ISM, the ATPase regulators, MS73, MSS1, TBP1 and mts2, remain at low levels in 26S proteasomes in FM from developmental Stage-0 to Stage-7. The non-ATPase regulator subunit 5a, which binds to multiubiquitin chains, increased in ISM similarly to the ATPases but not in FM. The ecdysteroid agonist RH-5849 prevented these subunit increases in ISM. These findings show that reprogramming of 26 S proteasomes is involved in the specific elimination of ISM during eclosion and does not occur in FM which are needed for adult moth flight.

Animals↗

PubMed2006

Cell-cell fusion as a means to establish pluripotency.

Embryonic stem cells (ESCs), embryonic germ cells (EGCs), and embryonic carcinoma cells (ECCs) are three types of pluripotent cells derived from mammalian embryos. The three cell types are capable not only of self-renewal, but also of having the potential to give rise to cells of all tissue types in the fetal and adult body. In several reports, ESCs, ECCs, and EGCs have been described to reprogram somatic cells in vitro. After reprogramming caused by fusion, somatic cells exhibit various features of pluripotent cells: expression of pluripotency markers (e.g., Oct4, nanog, and Rex-1), absence of tissue-specific gene expression, reactivation of inactive X chromosome of female somatic cells, demethylation, as well as histone modification. An activity in pluripotent stem cells appears to be capable of inducing the global changes inherent in the reprogramming of somatic cells. Investigations involving pluripotent stem cells will yield substantial insight into various fundamental biological processes, such as cellular differentiation and de-differentiation. Most importantly for the public, however, is that such studies might lead into cell-based therapies and as such have the potential to change regenerative medicine.

Animals↗

PubMed2005

The use of Xenopus oocytes and embryos as a route towards cell replacement.

When nuclei of somatic cells are transplanted to enucleated eggs of Xenopus, a complete reprogramming of nuclear function can take place. To identify mechanisms of nuclear reprogramming, somatic nuclei can be transplanted to growing meiotic oocytes of Xenopus, and stem cell genes activated without DNA replication. The combination of somatic cell nuclear transfer with morphogen signalling and the community effect may lead towards the possibility of cell replacement therapy. When mechanisms of nuclear reprogramming are understood, it may eventually be possible to directly reprogramme human somatic cell nuclei without the use of eggs.

Animals↗

PubMed2007

Cloned blastocysts produced by nuclear transfer from somatic cells in cynomolgus monkeys (Macaca fascicularis).

In nonhuman primates (NHPs), there have so far been few reports about nuclear transfer (NT), especially using adult somatic cells. The objective of this study was to determine the developmental competence of NT embryos derived from various somatic cells embryonic stem (ES), amniotic epithelial, cumulus, or fetal fibroblast cells] and the nuclear transfer method, such as electro fusion or piezo microinjection, activation with chemical reagent [ionomycine/6-dimethylaminopurine (DMAP), calcium ionophore A23187/DMAP, or cycloheximide (CHX)] and reprogramming time (1, 2, or 4 h; in this study, the duration from injection or fusion to activation was defined as the reprogramming time). Our results showed that a 1-h reprogramming and activation with ionomycin/DMAP are suitable for NT in monkeys. Developing cleaved embryos up to the six-cell stage was similar among all experiments. However, beyond the eight-cell stage, developmental rates were higher in NT embryos reconstructed with fetal fibroblast cells and amniotic epithelial cells, and we were able to produce NT blastocysts from these cells. Interestingly, electro fusion is sufficient for amniotic epithelial cells and piezo microinjection is better suited for fetal fibroblast cells to produce NT blastocysts, thus suggesting that the best method for somatic cell NT may be different between cell types.

Amnion↗

PubMed1993

Unique sensing errors in third-generation implantable cardioverter-defibrillators.

OBJECTIVES: Third-generation cardioverter-defibrillators appear to be susceptible to unique sensing errors. This study was performed to determine the incidence and types of sensing errors in combination therapy implantable devices. BACKGROUND: One of the advantages offered by third-generation implantable cardioverter-defibrillators is the combination of bradycardia and antitachycardia pacing and cardioversion-defibrillation capabilities in a single device. The potential for unique sensing errors, those caused by the conflicts presented by combining bradycardia and tachycardia sensing and therapy algorithms in the same device, has not been previously addressed. METHODS: To determine the incidence of important sensing errors, 61 patients with a combination therapy device (Cadence [Ventritex] and PCD [Medtronic]) were studied for a 25-month period. In addition to surface electrocardiographic recordings during implantation and routine device testing, real-time and stored electrograms recorded from the rate-sensing leads (Cadence) and real-time marker channel recordings (PCD) were reviewed to diagnose sensing errors that resulted in symptoms, device inefficacy or delivery of inappropriate therapy. After recognition, specific reprogramming steps were performed in an attempt to avoid recurrent sensing errors. RESULTS: A total of 13 sensing errors were diagnosed in 12 patients (19.7%); the incidence was similar in both devices. Five distinct categories of sensing errors were identified. After device reprogramming, only one recurrent error occurred in 98 patient-months of follow-up. CONCLUSIONS: Important sensing errors occur in approximately 20% of patients with third-generation combination therapy cardioverter-defibrillators. Prompt diagnosis of sensing errors can lead to specific reprogramming steps to avoid recurrent errors.

Algorithms↗

PubMed2006

The developmental competence of bovine nuclear transfer embryos derived from cow versus heifer cytoplasts.

Due to its economic importance, the production of cattle by nuclear transfer has been a primary research focus for many researchers during the past few years. While many groups have successfully produced cattle by nuclear transfer, and progress in this area continues, nuclear transfer remains a very inefficient technology. This study evaluates the effect of the oocyte source (cow and heifer) on the developmental competence of nuclear transfer embryos. In order for nuclear transfer to be successful, a differentiated donor cell must be reprogrammed and restored to a totipotent state. This reprogramming is probably accomplished by factors within the oocyte cytoplasm. This study indicates that oocytes derived from cows have a greater capacity to reprogram donor cell DNA following nuclear transfer as compared to heifer oocytes based on in vitro development to the 2-cell stage and to the compacted morula/blastocyst stages. Nuclear transfer embryos derived from cow oocytes resulted in significantly higher rates of pregnancy establishment than embryos derived from heifer oocytes and resulted in higher pregnancy retention at 90 and 180 days and a greater number of term deliveries. Following delivery more calves derived from cow oocytes tended to be healthy and normal than those derived from heifer oocytes. The differences in developmental efficiency between nuclear transfer embryos derived from cow and heifer cytoplasts demonstrate that subtle differences in oocyte biology can have significant effects on subsequent development of nuclear transfer embryos.

Aging↗