The role of oxidative stress and antioxidant supplementation in pregnancy disorders

Oxidative stress is widely implicated in failed reproductive performance including infertility, miscarriage, diabetes-related congenital malformations and preeclampsia. Maternal obesity is a strong risk factor for preeclampsia, and recently, in an animal model of maternal obesity we have reported evidence of oxidative stress in the oocytes of obese animals prior to pregnancy as well as in early stage embryos. This adds to the growing evidence for a greater focus on the pre-conceptual period in prevention of pregnancy disorders including those related to oxidative stress. Our research has also focussed on the role of free radicals and antioxidant capacity in preeclampsia. Assessment by measurement of markers of lipid peroxidation or of antioxidant capacity has provided unequivocal evidence for oxidative stress in this disorder. Partial failure of the process of placentation has been implicated, with recent evidence proposing that ischaemia-reperfusion in the placenta may contribute to oxidative stress in trophoblast. Endoplasmic reticulum stress in the placenta may also play a role. We and others have performed randomised controlled trials to determine whether early supplementation with vitamins C and E in women at risk of preeclampsia may be beneficial but these studies have shown no evidence for prevention of preeclampsia. Whether this represents an inappropriate antioxidant strategy or whether supplementation has been too late in gestation to be beneficial is not known. Other potential approaches to prevention of preeclampsia through amelioration of oxidative stress include provision of supplements in the pre-conceptual period, selenium supplements, anti-peroxynitrite strategies and statins

Phenological shifts of abiotic events, producers and consumers across a continent

Ongoing climate change can shift organism phenology in ways that vary depending on species, habitats and climate factors studied. To probe for large-scale patterns in associated phenological change, we use 70,709 observations from six decades of systematic monitoring across the former Union of Soviet Socialist Republics. Among 110 phenological events related to plants, birds, insects, amphibians and fungi, we find a mosaic of change, defying simple predictions of earlier springs, later autumns and stronger changes at higher latitudes and elevations. Site mean temperature emerged as a strong predictor of local phenology, but the magnitude and direction of change varied with trophic level and the relative timing of an event. Beyond temperature-associated variation, we uncover high variation among both sites and years, with some sites being characterized by disproportionately long seasons and others by short ones. Our findings emphasize concerns regarding ecosystem integrity and highlight the difficulty of predicting climate change outcomes. The authors use systematic monitoring across the former USSR to investigate phenological changes across taxa. The long-term mean temperature of a site emerged as a strong predictor of phenological change, with further imprints of trophic level, event timing, site, year and biotic interactions.Peer reviewe

Chronicles of nature calendar, a long-term and large-scale multitaxon database on phenology

We present an extensive, large-scale, long-term and multitaxon database on phenological and climatic variation, involving 506,186 observation dates acquired in 471 localities in Russian Federation, Ukraine, Uzbekistan, Belarus and Kyrgyzstan. The data cover the period 1890-2018, with 96% of the data being from 1960 onwards. The database is rich in plants, birds and climatic events, but also includes insects, amphibians, reptiles and fungi. The database includes multiple events per species, such as the onset days of leaf unfolding and leaf fall for plants, and the days for first spring and last autumn occurrences for birds. The data were acquired using standardized methods by permanent staff of national parks and nature reserves (87% of the data) and members of a phenological observation network (13% of the data). The database is valuable for exploring how species respond in their phenology to climate change. Large-scale analyses of spatial variation in phenological response can help to better predict the consequences of species and community responses to climate change.Peer reviewe

Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes.

The negative impact of obesity on reproductive success is well documented but the stages at which development of theconceptus is compromised and the mechanisms responsible for the developmental failure still remain unclear. Recentfindings suggest that mitochondria may be a contributing factor. However to date no studies have directly addressed theconsequences of maternal obesity on mitochondria in early embryogenesis. Using an established murine model ofmaternal diet induced obesity and a live cell dynamic fluorescence imaging techniques coupled with molecular biology wehave investigated the underlying mechanisms of obesity-induced reduced fertility. Our study is the first to show thatmaternal obesity prior to conception is associated with altered mitochondria in mouse oocytes and zygotes. Specifically,maternal diet-induced obesity in mice led to an increase in mitochondrial potential, mitochondrial DNA content andbiogenesis. Generation of reactive oxygen species (ROS) was raised while glutathione was depleted and the redox statebecame more oxidised, suggestive of oxidative stress. These altered mitochondrial properties were associated withsignificant developmental impairment as shown by the increased number of obese mothers who failed to supportblastocyst formation compared to lean dams. We propose that compromised oocyte and early embryo mitochondrialmetabolism, resulting from excessive nutrient exposure prior to and during conception, may underlie poor reproductiveoutcomes frequently reported in obese wome

Maternal weights and metabolic parameters.

<p>Data expressed as mean ± SEM. All serum measurements were fasting. Values in parentheses indicate n/group.</p

Maternal diet induced obesity increases rates of ROS generation and depletes glutathione in oocytes and zygotes.

<p>Cytosolic ROS production in oocytes and zygotes was measured by rate of oxidation of HEt. The traces represent changes of HEt fluorescence in oocytes (A) and zygotes (B) from lean (n = 15 cells/group) and obese (n = 15 cells/group) mice as a function of time. These data are summarised in histograms (C, D), in which the mean rates of ROS production are shown as the mean rate of HEt fluorescence change per minute. Results are expressed as percentage changes from HEt fluorescence in lean oocytes. Intracellular glutathione staining with MCB in oocytes (E) and zygotes (F) recovered from lean and obese female mice. Relative intensity of MCB fluorescence is expressed as a percentage of the signal from oocytes of lean mice. (G) Representative confocal images of GSH staining in oocytes. *<i>p</i><0.05, ** <i>p</i><0.01. Data are mean ± SEM.</p

Genes investigated and relevant primer sequences.

<p>Genes investigated and relevant primer sequences.</p