Fetal Liver Bisphenol A Concentrations and Biotransformation Gene Expression Reveal Variable Exposure and Altered Capacity for Metabolism in Humans

Widespread exposure to the endocrine active compound, bisphenol A (BPA), is well documented in humans. A growing body of literature suggests adverse health outcomes associated with varying ranges of exposure to BPA. In the current study, we measured the internal dose of free BPA and conjugated BPA and evaluated gene expression of biotransformation enzymes specific for BPA metabolism in 50 first‐ and second‐trimester human fetal liver samples. Both free BPA and conjugated BPA concentrations varied widely, with free BPA exhibiting three times higher concentrations than conjugated BPA concentrations. As compared to gender‐matched adult liver controls, UDP‐glucuronyltransferase, sulfotransferase, and steroid sulfatase genes exhibited reduced expression whereas β‐glucuronidase mRNA expression remained unchanged in the fetal tissues. This study provides evidence that there is considerable exposure to BPA during human pregnancy and that the capacity for BPA metabolism is altered in the human fetal liver. © 2012 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:116‐123, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21459Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96672/1/jbt21459.pd

Reliable Detection of Paternal SNPs within Deletion Breakpoints for Non-Invasive Prenatal Exclusion of Homozygous α0-Thalassemia in Maternal Plasma

Reliable detection of large deletions from cell-free fetal DNA (cffDNA) in maternal plasma is challenging, especially when both parents have the same deletion owing to a lack of specific markers for fetal genotyping. In order to evaluate the efficacy of a non-invasive prenatal diagnosis (NIPD) test to exclude α-thalassemia major that uses SNPs linked to the normal paternal α-globin allele, we established a novel protocol to reliably detect paternal SNPs within the (−−SEA) breakpoints and performed evaluation of the diagnostic potential of the protocol in a total of 67 pregnancies, in whom plasma samples were collected prior to invasive obstetrics procedures in southern China. A group of nine SNPs identified within the deletion breakpoints were scanned to select the informative SNPs in each of the 67 couples DNA by multiplex PCR based mini-sequencing technique. The paternally inherited SNP allele from cffDNA was detected by allele specific real-time PCR. A protocol for reliable detection of paternal SNPs within the (−−SEA) breakpoints was established and evaluation of the diagnostic potential of the protocol was performed in a total of 67 pregnancies. In 97% of the couples one or more different SNPs within the deletion breakpoint occurred between paternal and maternal alleles. Homozygosity for the (−−SEA) deletion was accurately excluded in 33 out of 67 (49.3%, 95% CI, 25.4–78.6%) pregnancies through the implementation of the protocol. Protocol was completely concordant with the traditional reference methods, except for two cases that exhibited uncertain results due to sample hemolysis. This method could be used as a routine NIPD test to exclude gross fetal deletions in α-thalassemia major, and could further be employed to test for other diseases due to gene deletion

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

Noninvasive prenatal diagnosis experience in the Cukurova Region of Southern Turkey: detecting paternal mutations of sickle cell anemia and beta-thalassemia in cell-free fetal DNA using high-resolution melting analysis

WOS: 000326106700008PubMed ID: 23836351ObjectiveThis study used a high-resolution melting (HRM) technique to detect paternal mutations for the noninvasive prenatal diagnosis (NIPD) of -thalassemia and sickle cell anemia (HbS). We also determined the levels of cell-free fetal DNA and total cell-free DNA. MethodsWe used the HRM technique for fetal genotyping of paternal mutations in maternal plasma from 32 pregnancies at risk of -thalassemia and 57 pregnancies at risk of HbS. The DNA levels in maternal plasma were measured using real-time quantitative PCR. Multiples of the median (MoM) values were calculated in women at risk for -thalassemia or HbS. ResultsTwenty-two paternal mutations were detected in 89 pregnant women. Although we were successfully able to detect the paternal -thalassemia mutations, the mutant HbS fetuses could not be distinguished from maternal background in the early weeks of pregnancy. The detection of DYS14 in male fetuses was 100%. The MoM values of women at high risk of having HbS-affected fetuses were higher than those for the other groups. ConclusionHigh-resolution melting is a useful method for NIPD of -thalassemias by detecting paternal mutations in the maternal plasma. Cell-free fetal DNA quantification and MoM values were not informative for HbS or -thalassemias in early pregnancy. (c) 2013 John Wiley & Sons, Ltd.Cukurova University Academic Research Projects UnitCukurova UniversityThis study was supported by the Cukurova University Academic Research Projects Unit