Deletion of Chdh (Choline dehydrogenase) in Mice Does Not Alter Brain Mitosis and Apoptosis

Choline is an essential nutrient. Large amounts of choline are delivered across the placenta to the developing fetus, contributing to brain development and, consequently, affecting memory performance during adulthood. Rodent studies have described specific epigenetic mechanisms, whereby choline deprivation altered the neurobiology of progenitor cells, modifying their proliferation and survival. Choline, via oxidation to betaine, provides one-carbon units to the methionine cycle and further, to all methylation processes part of the epigenetic control. We found that the choline dehydrogenase (Chdh) gene, responsible for this conversion, is expressed in the brain of adult and fetal mice. By deleting the Chdh gene, we investigated the effects of low betaine synthesis on fetal brain development. We assessed cell proliferation in Chdh+/+ and Chdh-/- fetuses at embryonic day 17 (E17) by immunohistochemistry. Mitosis and apoptosis were not significantly altered by fetal genotype. Further studies will be needed to establish if gene-specific methylation is altered between Chdh wildtype and knockout mice fetuses.Master of Scienc

Choline Dehydrogenase Polymorphism rs12676 Is a Functional Variation and Is Associated with Changes in Human Sperm Cell Function

Approximately 15% of couples are affected by infertility and up to half of these cases arise from male factor infertility. Unidentified genetic aberrations such as chromosomal deletions, translocations and single nucleotide polymorphisms (SNPs) may be the underlying cause of many cases of idiopathic male infertility. Deletion of the choline dehydrogenase (Chdh) gene in mice results in decreased male fertility due to diminished sperm motility; sperm from Chdh−/− males have decreased ATP concentrations likely stemming from abnormal sperm mitochondrial morphology and function in these cells. Several SNPs have been identified in the human CHDH gene that may result in altered CHDH enzymatic activity. rs12676 (G233T), a non-synonymous SNP located in the CHDH coding region, is associated with increased susceptibility to dietary choline deficiency and risk of breast cancer. We now report evidence that this SNP is also associated with altered sperm motility patterns and dysmorphic mitochondrial structure in sperm. Sperm produced by men who are GT or TT for rs12676 have 40% and 73% lower ATP concentrations, respectively, in their sperm. rs12676 is associated with decreased CHDH protein in sperm and hepatocytes. A second SNP located in the coding region of IL17BR, rs1025689, is linked to altered sperm motility characteristics and changes in choline metabolite concentrations in sperm

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Some recent evidence of the presence of the Critically Endangered Gyps vulture populations in northern Shan State, Myanmar

Presence of the Critically Endangered Gyps vulture populations in northern Shan State, Myanmar. On 27 November 2018, we observed a flock of G. bengalensis, G. tenuirostris, and G. himalayanensis in Man Sant Village, Mong Yai Township, Northern Shan State, Myanmar. The most notable feature of our observation was the presence of G. bengalensis and G. tenuirostris: we could observe as many as 38 vultures of three species

Expression of CHDH protein is decreased in sperm and primary hepatocytes from humans who are heterozygous or homozygous for the rs12676 SNP.

<p>The abundance of CHDH protein in sperm (A) and primary hepatocyte (B) lysates was measured by western blot. Blots were probed for ∝-TUBULIN (sperm) or β-ACTIN (hepatocytes) and data presented are the mean ± SEM of the ratio of CHDH: ∝-TUBULIN or CHDH:β-ACTIN protein. Statistical differences were tested by ANOVA and Student's <i>t</i> test. * indicates different from GG, p-value <0.05. ** indicates different from GG, p-value <0.01. N = 3 per genotype.</p

Sperm mitochondrial morphology and ATP concentrations are not changed in samples from men who are homozygous for rs1025689, but not rs12676.

<p><i>A.</i> Representative longitudinal section of sperm midpiece. <i>B.</i> Representative cross-sectional section of sperm midpiece. Arrows indicate mitochondria. <i>C.</i> ATP concentrations as measured previously; “CC" group only contains data from men who are CC for rs1025689 and not TT for rs12676. Data presented are mean ± SEM. N = 9 (GG), 22 (GC) and 5 (CC).</p

Characteristics of the study population.

<p>Average age, average number of biological children per subject and occurrence of abnormal semen characteristics or infertility were calculated from self-reported information. N = 79, except for average number of biological children, which was calculated only in men who answered this question (N = 71).</p

rs12676 TT genotype is associated with dysmorphic mitochondrial structure in sperm.

<p>Sperm were fixed and processed for transmission electron microscopy as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036047#s2" target="_blank">Methods</a> section. Longitudinal and cross-sectional sections of sperm were examined for mitochondria structure anomalies. Representative images for rs12676 genotypes (GG, panel <i>A</i> and <i>D</i>; GT, panel <i>B</i> and <i>E</i>; TT, panel <i>C</i> and <i>F</i>) are shown. N = 5 per genotype. Micrographs shown are at 80,000× magnification and arrows indicate mitochondria.</p