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At least 217 records · Page 12

The epigenetic effects of a high prenatal folate intake in male mouse fetuses exposed in utero to arsenic

Inorganic arsenic (iAs) is a complete transplacental carcinogen in mice. Previous studies have demonstrated that in utero exposure to iAs promotes cancer in adult mouse offspring, possibly acting through epigenetic mechanisms. Humans and rodents enzymatically convert iAs to its methylated metabolites. This reaction requires S-adenosylmethionine (SAM) as methyl group donor. SAM is also required for DNA methylation. Supplementation with folate, a major dietary source of methyl groups for SAM synthesis, has been shown to modify iAs metabolism and the adverse effects of iAs exposure. However, effects of gestational folate supplementation on iAs metabolism and fetal DNA methylation have never been thoroughly examined. In the present study, pregnant CD1 mice were fed control (i.e. normal folate, or 2.2 mg/kg) or high folate diet (11 mg/kg) from gestational day (GD) 5 to 18 and drank water with 0 or 85 ppm of As (as arsenite) from GD8 to 18. The exposure to iAs significantly decreased body weight of GD18 fetuses and increased both SAM and S-adenosylhomocysteine (SAH) concentrations in fetal livers. High folate intake lowered the burden of total arsenic in maternal livers but did not prevent the effects of iAs exposure on fetal weight or hepatic SAM and SAH concentrations. In fact, combined folate-iAs exposure caused further significant body weight reduction. Notably, iAs exposure alone had little effect on DNA methylation in fetal livers. In contrast, the combined folate-iAs exposure changed the CpG island methylation in 2,931 genes, including genes known to be imprinted. Most of these genes were associated with neurodevelopment, cancer, cell cycle, and signaling networks. The canonical Wnt-signaling pathway, which regulates fetal development, was among the most affected biological pathways. Taken together, our results suggest that a combined in utero exposure to iAs and a high folate intake may adversely influence DNA methylation profiles and weight of fetuses, compromising fetal development and possibly increasing the risk for early-onset of disease in offspring. Highlights: ► We used transplacental CD1 mice model for inorganic arsenic (iAs) carcinogenesis. ► We examined the effects of gestational iAs and high folate exposure on DNA methylation. ► iAs–folate interaction resulted in low fetal weights and changes in DNA methylation. ► Epigenetically altered genes were associated with cancer and neurodevelopment. ► We showed that in utero iAs–folate interaction negatively affects fetal development.

60 APPLIED LIFE SCIENCES↗

A mouse model of pre-pregnancy maternal obesity combined with offspring exposure to a high-fat diet resulted in cognitive impairment in male offspring

Cognitive impairment is a brain dysfunction characterized by neuropsychological deficits in attention, working memory, and executive function. Maternal obesity and consumption of a high-fat diet (HFD) in the offspring has been suggested to have detrimental consequences for offspring cognitive function through its effect on the hippocampus and prefrontal cortex. Therefore, our study aimed to investigate the effects of maternal obesity and offspring HFD exposure on the brain metabolome of the offspring.

60 APPLIED LIFE SCIENCES↗

Male–female communication triggers calcium signatures during fertilization in Arabidopsis

Cell–cell communication and interaction is critical during fertilization and triggers free cytosolic calcium ([Ca2 þ ]cyto) as a key signal for egg activation and a polyspermy block in animal oocytes. Fertilization in flowering plants is more complex, involving interaction of a pollen tube with egg adjoining synergid cells, culminating in release of two sperm cells and their fusion with the egg and central cell, respectively. Here, we report the occurrence and role of [Ca2 þ ]cyto signals during the entire double fertilization process in Arabidopsis. [Ca2 þ ]cyto oscillations are initiated in synergid cells after physical contact with the pollen tube apex. In egg and central cells, a short [Ca2 þ ]cyto transient is associated with pollen tube burst and sperm cell arrival. A second extended [Ca2 þ ]cyto transient solely in the egg cell is correlated with successful fertilization. Thus, each female cell type involved in double fertilization displays a characteristic [Ca2 þ ]cyto signature differing by timing and behaviour from [Ca2 þ ]cyto waves reported in mammals.

59 BASIC BIOLOGICAL SCIENCES↗