Seawater redox variations during the deposition of the Kimmeridge Clay Formation, United Kingdom (Upper Jurassic): evidence from molybdenum isotopes and trace metal ratios

The Kimmeridge Clay Formation (KCF) and its equivalents worldwide represent one of the most prolonged periods of organic carbon accumulation of the Mesozoic. In this study, we use the molybdenum (Mo) stable isotope system in conjunction with a range of trace metal paleoredox proxies to assess how seawater redox varied both locally and globally during the deposition of the KCF. Facies with lower organic carbon contents (TOC 1–7 wt %) were deposited under mildly reducing (suboxic) conditions, while organic-rich facies (TOC >7 wt %) accumulated under more strongly reducing (anoxic or euxinic) local conditions. Trace metal abundances are closely linked to TOC content, suggesting that the intensity of reducing conditions varied repeatedly during the deposition of the KCF and may have been related to orbitally controlled climate changes. Long-term variations in ?98/95Mo are associated with the formation of organic-rich intervals and are related to third-order fluctuations in relative sea level. Differences in the mean ?98/95Mo composition of the organic-rich intervals suggest that the global distribution of reducing conditions was more extensive during the deposition of the Pectinatites wheatleyensis and lower Pectinatites hudlestoni zones than during the deposition of the upper Pectinatites hudlestoni and Pectinatites pectinatus zones. The global extent of reducing conditions during the Kimmerigidan was greater than today but was less widespread than during the Toarcian (Early Jurassic) oceanic anoxic event. This study also demonstrates that the Mo isotope system in Jurassic seawater responded to changes in redox conditions in a manner consistent with its behavior in present-day sedimentary environment

Down-regulation of the histone methyltransferase EZH2 contributes to the epigenetic programming of decidualizing human endometrial stromal cells

Differentiation of human endometrial stromal cells (HESC) into decidual cells represents a highly coordinated process essential for embryo implantation. We show that decidualizing HESC down-regulate the histone methyltransferase enhancer of Zeste homolog 2 (EZH2), resulting in declining levels of trimethylation of histone 3 on lysine 27 (H3K27me3) at the proximal promoters of key decidual marker genes PRL and IGFBP1. Loss of H3K27me3 was associated with a reciprocal enrichment in acetylation of the same lysine residue, indicating active remodeling from repressive to transcriptionally permissive chromatin. Chromatin immunoprecipitation coupled with DNA microarray analysis demonstrated that decidualization triggers genome-wide changes in H3K27me3 distribution that only partly overlap those observed upon EZH2 knockdown in undifferentiated HESC. Gene ontology revealed that gain of the repressive H3K27me3 mark in response to decidualization and upon EZH2 knockdown in undifferentiated cells was enriched at the promoter regions of genes involved in transcriptional regulation and growth/cell proliferation, respectively. However, loss of the H3K27me3 mark (indicating increased chromatin accessibility) in decidualizing cells and upon EZH2 knockdown occurred at selective loci enriched for genes functionally implicated in responses to stimulus. In agreement, EZH2 knockdown in undifferentiated HESC was sufficient to augment the induction of decidual marker genes in response to cyclic AMP and progesterone signaling. Thus, loss of EZH2-dependent methyltransferase activity in the endometrium is integral to the process of chromatin remodeling that enables the transition from a proliferative to a decidual phenotype in response to differentiation cues

Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): an open-label, randomised controlled trial

Background: There is little evidence to guide the management of women with hypertensive disorders in late preterm pregnancy. We investigated the effect of immediate delivery versus expectant monitoring on maternal and neonatal outcomes in such women. Methods We did an open-label, randomised controlled trial, in seven academic hospitals and 44 non-academic hospitals in the Netherlands. Women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation were randomly allocated to either induction of labour or caesarean section within 24 h (immediate delivery) or a strategy aimed at prolonging pregnancy until 37 weeks of gestation (expectant monitoring). The primary outcomes were a composite of adverse maternal outcomes (thromboembolic disease, pulmonary oedema, eclampsia, HELLP syndrome, placental abruption, or maternal death), and neonatal respiratory distress syndrome, both analysed by intention-to-treat. This study is registered with the Netherlands Trial Register (NTR1792). Findings Between March 1, 2009, and Feb 21, 2013, 897 women were invited to participate, of whom 703 were enrolled and randomly assigned to immediate delivery (n=352) or expectant monitoring (n=351). The composite adverse maternal outcome occurred in four (1·1%) of 352 women allocated to immediate delivery versus 11 (3·1%) of 351 women allocated to expectant monitoring (relative risk [RR] 0·36, 95% CI 0·12–1·11; p=0·069). Respiratory distress syndrome was diagnosed in 20 (5·7%) of 352 neonates in the immediate delivery group versus six (1·7%) of 351 neonates in the expectant monitoring group (RR 3·3, 95% CI 1·4–8·2; p=0·005). No maternal or perinatal deaths occurred. Interpretation For women with non-severe hypertensive disorders at 34–37 weeks of gestation, immediate delivery might reduce the already small risk of adverse maternal outcomes. However, it significantly increases the risk of neonatal respiratory distress syndrome, therefore, routine immediate delivery does not seem justified and a strategy of expectant monitoring until the clinical situation deteriorates can be considered.Kim Broekhuijsen, MDt, Gert-Jan van Baaren, MDa, Maria G van Pampus, MDc, Wessel Ganzevoort, MDa, J Marko Sikkema, MDd, Mallory D Woiski, MDe, Martijn A Oudijk, MDf, Kitty W M Bloemenkamp, MDg, Hubertina C J Scheepers, MDh, Henk A Bremer, MDi, Robbert J P Rijnders, MDj, Aren J van Loon, MDk, Denise A M Perquin, MDl, Jan M J Sporken, MDm, Dimitri N M Papatsonis, MDn, Marloes E van Huizen, MDo, Corla B Vredevoogd, MDp, Jozien T J Brons, MDq, Mesrure Kaplan, MDr, Prof Anton H van Kaam, MDb, Henk Groen, MDs, Martina M Porath, MDu, Prof Paul P van den Berg, MDt, Prof Ben W J Mol, MDv, Maureen T M Franssen, MDt, Josje Langenveld, M

Effect of cyclic AMP and estrogen/progesterone on the transcription of DNA methyltransferases during the decidualization of human endometrial stromal cells

Progesterone, estrogen and cyclic adenosine monophosphate (cAMP) together regulate the decidualization of human endometrial stromal cells in a time-dependent manner. The role of DNA methylation and the three active DNA methyltransferases (DNMTs) in the regulation of decidualization is gaining interest but the exact role of this epigenetic mechanism during decidualization is largely unknown. We aimed to understand the effect of the main regulators of decidualization on the expression of the DNMTs and in turn on the expression of steroid hormone receptors during the decidualization. We conducted a time-course analysis from 6 h to 10 days to examine the change in gene expression of the DNMTs and the steroid hormone receptors over time in response to estradiol, medroxy-progesterone acetate (MPA) and dibutyryl-cAMP (db-cAMP) in a human endometrial stromal cells (HESC) cell line. Only the combination treatment with MPA-mix (estradiol + MPA + db-cAMP) up-regulated ERα PGR, progesterone receptor B (PRB) and androgen receptor at 24 h. Both decidualization pathways of db-cAMP and estradiol/MPA, independently and combined, consistently down-regulated DNMT3B mRNA expression from 6 h till 10 days, whereas DNMT1 and DNMT3A mRNA expression were down-regulated transiently. Forced expression of DNMT3B in HESC for 10 days attenuated IGFBP1 mRNA and protein expression; and forced expression of DNMT3B combined with MPA-mix treatment synergistically increased the expression of PRB at 24 h. The HESC morphology and proliferation remained unchanged in response to forced expression of DNMT3B. In conclusion, mRNA expression of the DNMTs during decidualization is dynamic, so that expression varies according to the cAMP or estradiol/MPA pathway treatments that regulate them in a time-dependent manner. Although forced expression of DNMT3B by itself is insufficient to inhibit decidualization, forced expression of DNMT3B in combination with MPA-mix synergistically up-regulated PRB, as well as attenuated the expression of IGFBP1, the decidualization marker

Assessing the distribution of sedimentary C40 carotenoids through time

© 2015 John Wiley & Sons Ltd. A comprehensive marine biomarker record of green and purple sulfur bacteria (GSB and PSB, respectively) is required to test whether anoxygenic photosynthesis represented a greater fraction of marine primary productivity during the Precambrian than the Phanerozoic, as current models of ocean redox evolution suggest. For this purpose, we analyzed marine rock extracts and oils from the Proterozoic to the Paleogene for C40 diagenetic products of carotenoid pigments using new analytical methods. Gas chromatography coupled with tandem mass spectrometry provides a new perspective on the temporal distributions of carotenoid biomarkers for phototrophic sulfur bacteria, specifically okenane, chlorobactane, and paleorenieratane. According to conventional paleoredox interpretations, this revised stratigraphic distribution of the GSB and PSB biomarkers implies that the shallow sunlit surface ocean (<24 m) became sulfidic more frequently in the geologic past than was previously thought. We reexamine whether there is evidence supporting a planktonic source of GSB and PSB pigments in marine systems or whether additional factors are required to explain the marine phototrophic sulfur bacteria record. To date, planktonic GSB and PSB and their pigments have been identified in restricted basins and lakes, but they have yet to be detected in the unrestricted, transiently sulfidic, marine systems. Based on modern observations, additional environmental factors, including basin restriction, microbial mats, or sediment transport, may be required to fully explain GSB and PSB carotenoids in the geologic record