An update on maternal medication-related embryopathies

There is a general perception that any exposure to medication during pregnancy poses a potential risk to the fetus. Most available data about teratogenic drugs is derived from animal studies, case reports, or cohort studies. As a result, counseling women and their partners about the safety of drugs during pregnancy can be difficult due to limited information about efficacy, pharmacokinetics, and teratogenicity of some drugs. However, this should always be done in the context of weighing up potential teratogenic risks with the perinatal risks of an untreated medical or psychiatric condition. Ideally, this counseling should occur prior to a planned pregnancy so that medications and treatment of chronic medical conditions can be optimized. It is important that clinicians providing antenatal care are able to confidently manage women including utilizing appropriate resources. This paper aims at reviewing a selected (non-exhaustive) list of the most commonly prescribed medications considered significant human teratogens and provides recommendations for pre-conception and antenatal counseling.     

Non-invasive prenatal detection of achondroplasia in size-fractionated cell-free DNA by MALDI-TOF MS assay

Achondroplasia is the most common form of short-limbed dwarfism in humans and is caused by mutations in the FGFR3 gene. Currently, prenatal diagnosis of this disorder relies on invasive procedures. Recent studies have shown that fetal single gene point mutations could be detected in cell-free DNA (cf-DNA) from maternal plasma by either the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) assay with single allele base extension reaction (SABER) approach or the size fractionation of cf-DNA in maternal plasma. Here, we combined the two approaches to non-invasively examine the fetal G1138A mutation in maternal plasma. cf-DNA was extracted from maternal plasma samples obtained from two pregnant women at risk for achondroplasia. The fetal G1138A mutation was determined by the analysis of size-fractionated cf-DNA in maternal plasma using MALDI-TOF MS with SABER approach and homogenous MassEXTEND (hME) assay, respectively. The fetal G1138A mutation was detectable in the two achondroplasia-affected pregnancies by the analysis of cf-DNA in maternal plasma using MALDI-TOF MS. However, the size-fractionation approach led to a more precise detection of the fetal mutation in both analyses. This analysis would be suitable for non-invasive prenatal diagnosis of diseases caused by fetal single gene point mutations. Copyright © 2007 John Wiley & Sons, Ltd.     

Occurrence of DNA methylation in Daphnia magna and influence of multigeneration Cd exposure

Most of the research on the epigenetic phenomenon of DNA methylation has been performed with vertebrates and plants. Knowledge on DNA methylation in Daphnia magna, a key test organism in aquatic toxicology, is completely lacking. Through epigenetic inheritance, effects of transient chemical exposure could be transferred to non-exposed generations, which could have a major impact on ecological risk assessment procedures. In this study, we determined if CpG methylation occurs in D. magna and if this can be influenced by exposure to toxic substances. Homologs of human DNA methyltransferases DNMT1, DNMT2 and DNMT3A were found in the partially available D. magna genome. Using an optimized “Amplification of Intermethylated Sites (AIMS)” technique, two methylated fragments were discovered in D. magna DNA. No homology was found for these sequences. The methylation and the D. magna origin of the fragments were confirmed with Southern analysis. This optimized AIMS technique was then applied to DNA of D. magna which were exposed to 180 µg/L Cd for two generations. Exposure resulted in a significant decrease in reproduction. The same methylated fragments with the same band intensity were observed in DNA of both non-exposed and exposed daphnids. As such, it could not be demonstrated that Cd exposure altered DNA methylation. However, the presence of DNA methylation in D. magna shows that potentially epigenetic effects may occur in this species.     

A regional inventory and monitoring setup to evaluate bark peeling damage by red deer (Cervus elaphus) in coniferous plantations in Southern Belgium

Sediment phosphorus (P) fractions and sorption characteristics and P release from intact sediment cores of Baiyangdian Lake in North China in spring 2009 were investigated. Results of chemical fractionation showed that total P (TP) content in sediment ranged from 443 to 611 mg kg(?-1). Of the P fractions including inorganic P (IP) and organic P (OP), IP was a dominant component of TP and present in the form of P bounded to calcium (Ca-P) while the bioavailable P content bounded to Al, Fe, and Mn oxides and hydroxides (Fe/Al-P) varied from 14 to 102 mg kg(?-1). The batch experiments showed that the sediments had appreciable maximum P adsorption capacity from 141.86 to 377.37 mg kg(?-1). However, the zero P equilibrium concentration (C?(eq))in most sampling sites was larger than the P concentration in water column. Accordingly, the sediments from those sampling sites would release P into the overlying water at the positive P flux rates as a P release source. Significant positive correlation between P flux rates and Fe/Al-P revealed that the sediment P release would mainly originate from the bioavailable P fraction. It is evident that the inherent phosphorus present in lake sediments would be a major threat to the water quality and ecosystem reservation in Baiyangdian lake.