Age-Associated Metabolic and Morphologic Changes in Mitochondria of Individual Mouse and Hamster Oocytes

Background: In human oocytes, as in other mammalian ova, there is a significant variation in the pregnancy potential, with approximately 20% of oocyte-sperm meetings resulting in pregnancies. This frequency of successful fertilization decreases as the oocytes age. This low proportion of fruitful couplings appears to be influenced by changes in mitochondrial structure and function. In this study, we have examined mitochondrial biogenesis in both hamster (Mesocricetus auratus) and mouse (Mus musculus) ova as models for understanding the effects of aging on mitochondrial structure and energy production within the mammalian oocyte. Methodology/Principal Findings: Individual metaphase II oocytes from a total of 25 young and old mice and hamsters were collected from ovarian follicles after hormone stimulation and prepared for biochemical or structural analysis. Adenosine triphosphate levels and mitochondrial DNA number were determined within individual oocytes from young and old animals. In aged hamsters, oocyte adenosine triphosphate levels and mitochondrial DNA molecules were reduced 35.4% and 51.8%, respectively. Reductions of 38.4% and 44% in adenosine triphosphate and mitochondrial genomes, respectively, were also seen in aged mouse oocytes. Transmission electron microscopic (TEM) analysis showed that aged rodent oocytes had significant alterations in mitochondrial and cytoplasmic lamellae structure. Conclusions/Significance: In both mice and hamsters, decreased adenosine triphosphate in aged oocytes is correlated with a similar decrease in mtDNA molecules and number of mitochondria. Mitochondria in mice and hamsters undergo significant morphological change with aging including mitochondrial vacuolization, cristae alterations, and changes in cytoplasmic lamellae

Transmission of Mitochondrial DNA Diseases and Ways to Prevent Them

Recent reports of strong selection of mitochondrial DNA (mtDNA) during transmission in animal models of mtDNA disease, and of nuclear transfer in both animal models and humans, have important scientific implications. These are directly applicable to the genetic management of mtDNA disease. The risk that a mitochondrial disorder will be transmitted is difficult to estimate due to heteroplasmy—the existence of normal and mutant mtDNA in the same individual, tissue, or cell. In addition, the mtDNA bottleneck during oogenesis frequently results in dramatic and unpredictable inter-generational fluctuations in the proportions of mutant and wild-type mtDNA. Pre-implantation genetic diagnosis (PGD) for mtDNA disease enables embryos produced by in vitro fertilization (IVF) to be screened for mtDNA mutations. Embryos determined to be at low risk (i.e., those having low mutant mtDNA load) can be preferentially transferred to the uterus with the aim of initiating unaffected pregnancies. New evidence that some types of deleterious mtDNA mutations are eliminated within a few generations suggests that women undergoing PGD have a reasonable chance of generating embryos with a lower mutant load than their own. While nuclear transfer may become an alternative approach in future, there might be more difficulties, ethical as well as technical. This Review outlines the implications of recent advances for genetic management of these potentially devastating disorders

Prediction of fetal anemia by middle cerebral artery Doppler

Objectives: To assess the value of peak systolic velocity in the middle cerebral artery (MCA) in prediction of fetal anemia as a non invasive method in non hydropic fetuses. Methods: The study included 30 pregnant women with non hydropic fetuses and with known red cell antibodies. Full ultrasound examination was done and peak velocity of systolic cerebral blood flow in MCA was measured. If severe anemia was suspected, fetal blood sampling by cordocentesis was performed. Results: Thirty fetuses were examined, 22 were anemic and eight had a hemoglobin value within a normal range. The mean MCA peak systolic velocity for fetus with the normal hemoglobin (Hb) was 48.98 ± 13.94 while that for the anemic fetus was 64.79 ± 11.97 and P = 0.004. Sensitivity of increased peak velocity of systolic blood flow in MCA for prediction of fetal anemia was 90.5% and specificity was 78.6%. Conclusion: Doppler of peak velocity of systolic blood flow in MCA can be reliable in predicting anemia so delaying invasive methods until treatment (blood transfusion) is expected to be necessary

Hospital Mortality In Alwahda Hospital, Derna, Libya Based On A Ten-Year Review (1997-2006).

Background: The leading causes of mortality are very important parameters for the individual and society bases. It reflects the medical problems that need to be studied in order to organize future plan and strategy of the Health services by identifying the risk factors, precipitating causes and methods of prevention. Objectives: Analysis of hospital mortality helps to assess the standards of health-care delivery. Methods: This is a retrospective study evaluating the causes of deaths which occurred during the years 1997-2006 in Alwahda hospital, Derna, Libya. The leading causes of deaths were classified according to the nature of the disease and organ involvement. The causes of death were classified according to the International Statistical Classification of Diseases (ICD-10). Results: A total number of 1705 patients in Derna who died from 1997 to 2006 have been studied. The most common contributors of non-neoplasmatic causes of death were cardiovascular diseases (120-125) represented 36.1 % (615) of all deaths, followed by stroke and CVD (160- 169) by 18.2 % (311) while injury accidents (VO 1- Y98), cancer (COO-D48), renal diseases (N17-N19) and chest infections (110-118) represented 7.9% (133), 7.7% (132), 7.2% (120) and 6.1 % (105), respectively. Not written or found dead represented 5.9% (100) of all deaths. Males constituted 55.3% (942) and females 44.7% (763). The median age was 75.1 years (1 day - 100 years). The six most common ICD-10 chapters IX, II, IV, XI, XX, X, XIV included 87.8% of the total 1705 deaths. Diseases of the digestive system (KOOK93) were at 4.6% (54), diabetes mellitus, DKA (E10-E14) at 1.2% (21), and congenital and perinatal causes at 1.2% (20). Neoplasms caused 7.7% of the total 1705 deaths, with leading forms being the malignant neoplasm of OIT (C18-21.2) at 40.2%, lung (C34) 14.9%, breast 9.3%, renal 4.7%, prostate (C61) 3.5%, urinary bladder 2.3% and thyroid 1.2%. Conclusions: Disease specific characteristics, as well as functional and infrastructural inadequacies were identified and provided evidence for defining priorities and strategies for improving the standards of care. Effective transformation can promise better prospects. Keywords: Causes, Mortality, ICD 1 0, Hospital, Ischemic Heart Disease, Cerebrovascular Disease, Infection, Injuries, Accidents, Death Certificate