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Tuttelmann F.,University of Munster | Ivanov P.,Medical University-Pleven | Dietzel C.,University of Munster | Sofroniou A.,University of Munster | And 5 more authors.
Fertility and Sterility | Year: 2013

Objective To study the influence of M2/ANXA5 for recurrent pregnancy loss (RPL), according to the timing of miscarriages and assess the male partner risk. Design Genetic association study. Setting Academic research center. Patient(s) Female patients from two academic centers in Germany and Bulgaria with two or more unexplained miscarriages were selected for this study. Male partners were available for a part of the German sample. Population controls were recruited from healthy individuals of respective populations. Intervention(s) None. Main Outcome Measure(s) Incidence of M2 carriage and odds ratios were calculated between patient and control groups, and RPL risk was evaluated. Result(s) The M2 haplotype in ANXA5 was associated with greater overall RPL risk in German and in Bulgarian women, and a trend of higher prevalence was seen for male partners of German RPL patients. The highest relative risk of M2 carriage was observed in women of both populations with "early" fetal losses between the 10th and 15th gestational weeks, which was significant in the meta-analysis. Conclusion(s) M2 carriage seems to have an RPL risk role mostly for early abortions, gestational weeks 10-15. In the first phase of pregnancy this correlates with vascular remodeling to accomplish the transition from high- to low-resistance blood vessels. © 2013 by American Society for Reproductive Medicine. Source


Milic R.,University of Ljubljana | Martinovic J.,Belgrade Clinical Center | Dopsaj M.,University of Belgrade | Dopsaj V.,University of Belgrade | Dopsaj V.,Institute of Medical Biochemistry
European Journal of Applied Physiology | Year: 2011

We investigated the iron-related haematological parameters in both male and female athletes participating in different sporting disciplines necessitating different metabolic energy demands. A total of 873 athletes (514 males, mean age: 22.08 ± 4.95 years and 359 females, mean age: 21.38 ± 3.88 years) were divided according to gender and to the predominant energy system required for participation in sport (aerobic, anaerobic or mixed) and haematological and iron-related parameters were measured. For both male and female athletes, significant differences related to the predominant energy system were found at a general level: male (Wilks' λ = 0.798, F = 3.047, p < 0.001) and female (Wilks' λ = 0.762, F = 2.591, p < 0.001). According to the ferritin cutoff value of 35 μg/L, whole body iron and sTfR significantly differed in all three groups of male and female athletes (p < 0.001). The percentage of hypochromic erythrocytes in male athletes was significantly higher only in those who required an anaerobic energy source (p < 0.001), whilst in the females hypochromic erythrocytes (p < 0.001) and haemoglobin (anaerobic, p = 0.042; mixed, p = 0.006) were significantly different only in anaerobic and mixed energy source athletes. According to the ferritin cutoff value of 22 μg/L, in females, whole body iron, sTfR and hypochromic erythrocytes were significantly higher in all three groups of athletes than those below the aforementioned cutoff value (p < 0.001). We conclude that the predominant energy system required for participation in sport affects haematological parameters. sTfR and body iron proved to be reliable parameters for monitoring the dynamics of iron metabolism and could contribute to successful iron-deficiency prevention. © 2010 Springer-Verlag. Source


Dopsaj V.,Institute of Medical Biochemistry | Dopsaj V.,University of Belgrade | Martinovic J.,Belgrade Clinical Center | Stevuljevic J.K.,University of Belgrade | Bogavac-Stanojevic N.,University of Belgrade
International Journal of Sports Medicine | Year: 2011

The aim of the present study was to examine the association of proteins that regulate iron transport/storage content and acute phase response with oxidative stress in male and female athletes. Serum ferritin, transferrin, soluble transferrin receptor, C-reactive protein, interleukin-6 and oxidative stress parameters (reactive oxygen metabolites, superoxide anion, advanced oxidation protein products, lipid hydroperoxides, superoxide-dismutase and pro-oxidant-antioxidant balance) were determined in 138 athletes (73 females and 65 males). A general linear model indicated significant gender differences between athletes in terms of reactive oxygen metabolites (307.48±61.02 vs. 276.98±50.08; P=0.030), superoxide-dismutase (114.60±41.64 vs. 101.42±38.76; P=0.001), lipid hydroperoxides (149.84±38.95 vs. 101.43±39.26; P<0.001), pro-oxidant-antioxidant balance (512.40±148.67 vs. 413.09±120.30; P=0.002), advanced oxidation protein products (1.49±0.30 vs. 0.91±0.25; P<0.001) and superoxide (2.61±0.36 vs. 2.22±0.35; P=0.001), which were all significantly higher in females. Multivariate analysis of covariance indicated gender (P<0.001), training experience (P=0.004), C-reactive protein (P=0.002), soluble transferrin receptor (P=0.004) and transferrin (P<0.001) as significant covariates. Gender accounted for the largest proportion of variability for all oxidative stress parameters (46.3%) and female athletes were more susceptible to oxidative stress. Iron transport and storage proteins (transferrin and ferritin), but also acute phase reactants, were negatively related factors for oxidative stress. In conclusion, variation in the ferritin level may contribute to the different oxidative stress level between the sexes. © Georg Thieme Verlag KG Stuttgart middot; New York. Source


Hollmann M.,Institute of Animal Nutrition and Functional Plant Compounds | Miller I.,Institute of Medical Biochemistry | Hummel K.,Vetcore Facility for Research | Sabitzer S.,Vetcore Facility for Research | And 3 more authors.
PLoS ONE | Year: 2013

Energy-rich diets can challenge metabolic and protective functions of the rumen epithelial cells, but the underlying factors are unclear. This study sought to evaluate proteomic changes of the rumen epithelium in goats fed a low, medium, or high energy diet. Expression of protein changes were compared by two-dimensional differential gel electrophoresis followed by protein identification with matrix assisted laser desorption ionisation tandem time-of-flight mass spectrometry. Of about 2,000 spots commonly detected in all gels, 64 spots were significantly regulated, which were traced back to 24 unique proteins. Interestingly, the expression profiles of several chaperone proteins with important cellular protective functions such as heat shock cognate 71 kDa protein, peroxiredoxin-6, serpin H1, protein disulfide-isomerase, and selenium-binding protein were collectively downregulated in response to high dietary energy supply. Similar regulation patterns were obtained for some other proteins involved in transport or metabolic functions. In contrast, metabolic enzymes like retinal dehydrogenase 1 and ATP synthase subunit beta, mitochondrial precursor were upregulated in response to high energy diet. Lower expressions of chaperone proteins in the rumen epithelial cells in response to high energy supply may suggest that these cells were less protected against the potentially harmful rumen toxic compounds, which might have consequences for rumen and systemic health. Our findings also suggest that energy-rich diets and the resulting acidotic insult may render rumen epithelial cells more vulnerable to cellular damage by attenuating their cell defense system, hence facilitating the impairment of rumen barrier function, typically observed in energy-rich fed ruminants. © 2013 Hollmann et al. Source


Rogenhofer N.,Ludwig Maximilians University of Munich | Engels L.,Ludwig Maximilians University of Munich | Bogdanova N.,Institute of Human Genetics | Tuttelmann F.,Institute of Human Genetics | And 2 more authors.
Metabolism: Clinical and Experimental | Year: 2013

Objective The aim of this study was to analyze the contribution of the M2 haplotype of ANXA5 gene, previously identified as a risk factor for RPL and thrombophilia related pregnancy complications, to repeated miscarriage observed in PCOS patients. Patients/Methods 100 PCOS patients, 500 fertile women and 533 random population controls were genotyped for M2/ANXA5. Results M2 haplotype carriers faced a 3.4 fold elevated RPL risk (odds ratio 5.3, 95% confidence interval 3-9.2) compared to female fertile controls and 2.1 (odds ratio 2.6, 95% confidence interval 1.6-4.3) compared to population controls. The relative population risks in subgroups of PCOS patients with primary and secondary RPL were 2.3 (odds ratio 2.5, 95% confidence interval 1.2-5) and 3.3 (odds ratio 3.6, 95% confidence interval 1.5-8.4) respectively. As compared to the fertile women group, the relative risks equaled 4 (odds ratio 5, 95% confidence interval 2.3-10.8) and 6 (odds ratio 7.2, 95% confidence interval 3-17.7). Estimated relative risks for M2 carriers among PCOS RPL patients matched the values previously obtained for repeated miscarriage populations. The essential phenotypes, clinically defining PCOS, associated neither with RPL in their diagnostically relevant combinations, nor with M2 carriage as RPL risk factor in the PCOS RPL subgroups. Conclusions M2/ANXA5 seems an independent RPL risk factor in PCOS patients that progressively correlates with the number of first trimester pregnancies. From our pilot study in PCOS women it appears relevant to offer M2/ANXA5 diagnostic analysis to such patients with RPL complications, to possibly guide proper therapeutic decisions. © 2013 Elsevier Inc. Source

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