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Biomedical subjects

Susan Pickering

Publications and source records attributed to Susan Pickering.

6 recordsLinked to original sources
PubMed2004

Early embryo development is an indicator of implantation potential.

To maximize the chances of pregnancy during assisted reproduction treatment, it is important to be able to identify embryos with high implantation potential. Embryos which divide more quickly following insemination have been shown to produce higher pregnancy and implantation rates than those which divide later. The aim of this study was to compare the developmental potential of early cleaving embryos with those in which the pronuclear membranes had broken down at the time of scoring. Normally fertilized zygotes (n = 2447) were assessed 25-27 h post-insemination and categorized according to developmental stage (pronuclei visible, no pronuclei, or early cleavage to two cells). Pregnancy and implantation rates were assessed in cycles where embryos selected for transfer were at an equivalent stage 25-27 h post-insemination. A significantly higher implantation rate was achieved following transfer of either early cleavage embryos or those which had no pronuclei compared with embryos with intact pronuclei when assessed 25-27 h post-insemination/microinjection. The correlation between early cleavage and an improved pregnancy and implantation rate was confirmed. Scoring for the presence of early cleavage or status of pronuclei is quick and objective and provides information that may be used to discriminate between morphologically equivalent embryos at a later stage in development.

Blastocyst↗
PubMed2003

Strategies and outcomes of the first 100 cycles of preimplantation genetic diagnosis at the Guy's and St. Thomas' Center.

OBJECTIVE: To establish strategies for the implementation of a successful preimplantation genetic diagnosis (PGD) service. DESIGN: Retrospective review of data from a single center. SETTING: A United Kingdom National Health Service hospital. PATIENT(S): Patients (60 couples) were referred for PGD from UK genetic centers. INTERVENTION(S): We followed the protocol of ovarian stimulation, oocyte retrieval, fertilization, single cell biopsy on day 3, and embryo transfer on day 4. Pregnancies unaffected by the familial genetic condition. RESULT(S): A total of 60 couples was treated for 20 different conditions. Early cycles using nonsequential embryo culture media were less successful (13% pregnancy rate/embryo transfer) than later cycles using sequential media (33.5%). Ninety-four percent of embryos (n = 473) had a single cell removed at biopsy. The overall pregnancy rate was 24% per cycle started, 29% per egg collection, 38% per transfer, and 40% per couple treated. In one cycle, an affected pregnancy followed PGD for spinal muscular atrophy (SMA). CONCLUSION(S): The use of sequential media and single cell biopsy results in a successful PGD program with encouraging pregnancy rates.

Chromosome Aberrations↗
PubMed2002

Superoxide activates mitochondrial uncoupling proteins.

Uncoupling protein 1 (UCP1) diverts energy from ATP synthesis to thermogenesis in the mitochondria of brown adipose tissue by catalysing a regulated leak of protons across the inner membrane. The functions of its homologues, UCP2 and UCP3, in other tissues are debated. UCP2 and UCP3 are present at much lower abundance than UCP1, and the uncoupling with which they are associated is not significantly thermogenic. Mild uncoupling would, however, decrease the mitochondrial production of reactive oxygen species, which are important mediators of oxidative damage. Here we show that superoxide increases mitochondrial proton conductance through effects on UCP1, UCP2 and UCP3. Superoxide-induced uncoupling requires fatty acids and is inhibited by purine nucleotides. It correlates with the tissue expression of UCPs, appears in mitochondria from yeast expressing UCP1, and is absent in skeletal muscle mitochondria from UCP3 knockout mice. Our findings indicate that the interaction of superoxide with UCPs may be a mechanism for decreasing the concentrations of reactive oxygen species inside mitochondria.

Adipose Tissue, Brown↗
PubMed2002

Myocardial protection from ischemia/reperfusion injury by targeted deletion of matrix metalloproteinase-9.

OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) activity is up regulated in the heart subjected to ischemic insult. Whether increased MMP-9 activity contributes to acute myocardial injury after ischemia-reperfusion remains unknown. To investigate the role of MMP-9 in myocardial infarction, we utilized a MMP-9 knockout mouse. METHODS AND RESULTS: Standard homologous recombination in embryonic stem cells was used to generate a mouse lacking MMP-9. The left anterior descending coronary artery was occluded for 30 min followed by 24 h reperfusion, and the ischemic and infarct sizes were determined. Targeted deletion of MMP-9 protected the heart from no-flow ischemia-reperfusion-induced myocardial injury. The myocardial infarct size was reduced by 17.5% in MMP-9 heterozygotes (+/-) (P<0.01) and 35.4% in MMP-9 knockout (-/-) mice (P<0.01) versus the wild-type (+/+) mice, respectively. Analysis of MMP activity in myocardial extracts by zymography demonstrated that ischemia-reperfusion-induced expression of proMMP-9 and active MMP-9 was reduced by 77.8% (P<0.01) and 69.1% (P<0.001), respectively, in (+/-) mice compared to (+/+) mice, and was absent in (-/-) animals. The expression of TIMP-1, an endogenous inhibitor of MMP-9, was elevated 4.7-fold (P<0.05) and 21.4-fold (P<0.05) in the (+/-) and (-/-) mice, respectively, compared to (+/+) mice. Immunohistochemical analysis revealed that neutrophils were the primary cellular source of MMP-9, and less neutrophils were detected in the ischemic region of the heart following ischemia-reperfusion in (-/-) mice compared to (+/+) mice. Measurement of myeloperoxidase activity, a marker enzyme of neutrophils, demonstrated a 44% reduction in neutrophils infiltrated into the ischemic myocardium in the (-/-) mice compared to the (+/+) mice (P<0.05). CONCLUSION: These results suggest that MMP-9 plays an important role in ischemia-reperfusion-induced myocardial infarction and MMP-9 could be a target for prevention or treatment of acute ischemic myocardial injury.

Animals↗
PubMed2002

Preimplantation genetic diagnosis.

Preimplantation genetic diagnosis (PGD) is an evolving technique that provides a practical alternative to prenatal diagnosis and termination of pregnancy for couples who are at substantial risk of transmitting a serious genetic disorder to their offspring. Samples for genetic testing are obtained from oocytes or cleaving embryos after in vitro fertilization. Only embryos that are shown to be free of the genetic disorders are made available for replacement in the uterus, in the hope of establishing a pregnancy. PGD has provided unique insights into aspects of reproductive genetics and early human development, but has also raised important new ethical issues about assisted human reproduction.

Aneuploidy↗