The roles of glutathione peroxidases during embryo development

Abstract

Embryo development relies on the complex interplay of the basic cellular processes including proliferation, differentiation, and apoptotic cell death. Precise regulation of these events is the basis for the establishment of embryonic structures and the organ development. Beginning with fertilization of the oocyte until delivery the developing embryo encounters changing environmental conditions such as varying levels of oxygen, which can give rise to reactive oxygen species (ROS). These challenges are met by the embryo with metabolic adaptations and by an array of anti-oxidative mechanisms. ROS can be deleterious by modifying biological molecules including lipids, proteins, and nucleic acids and may induce abnormal development or even embryonic lethality. On the other hand ROS are vital players of various signaling cascades that affect the balance between cell growth, differentiation, and death. An imbalance or dysregulation of these biological processes may generate cells with abnormal growth and is therefore potentially teratogenic and tumorigenic. Thus, a precise balance between processes generating ROS and those decomposing ROS is critical for normal embryo development. One tier of the cellular protective system against ROS constitutes the family of selenium-dependent glutathione peroxidases (GPx). These enzymes reduce hydroperoxides to the corresponding alcohols at the expense of reduced glutathione. Of special interest within this protein family is the moonlighting enzyme glutathione peroxidase 4 (Gpx4). This enzyme is a scavenger of lipophilic hydroperoxides on one hand, but on the other hand can be transformed into an enzymatically inactive cellular structural component. GPx4 deficiency – in contrast to all other GPx family members – leads to abnormal embryo development and finally produces a lethal phenotype in mice. This review is aimed at summarizing the current knowledge on GPx isoforms during embryo development and tumor development with an emphasis on GPx4.

A YY1-dependent increase in aerobic metabolism is indispensable for intestinal organogenesis

“…Several recent studies have observed an association between metabolic state and developmental processes, including in hematopoietic, mesenchymal and neural lineages Ufer and Wang, 2011). In the mature intestine, where rapid growth in intestinal crypts feeds differentiated cells onto the villi, it was recently observed that the proliferating progenitor cells exhibit a more glycolytic metabolism than their differentiated counterparts (Stringari et al, 2012;Xiong et al, 2015).…”

Diselementosis as a risk factor of embryo loss in lactating cows

“…The deficiency of this hormone has a negative effect on the processes of cellular growth and tissue differentiation. The connection of a high frequency of embryonic death and fetal abortions with selenium and iodine deficiency was also shown in the works of other authors (26,27).…”

Diet affects the redox system in developing Atlantic cod (Gadus morhua) larvae

“…The ratios and levels of 2GSH/GSSG is the most important cellular redox couple, and a common measure used to assess the cellular redox environment [16]. The state of the redox environment is important for proper development in mammals [12]. In line with this, many genes coding for proteins that maintain the cellular redox system are dynamically regulated during fish embryonic and larval development [21][22][23].…”

“…The redox system was focused on due to its importance to overall health. The 100 redox system genes investigated were chosen based on their importance within the redox system and/or because of their membership to gene families that are important within the redox system [12,16,19,[21][22][23]. We found that rotifer-fed larvae had a more reduced cellular environment during development, and had elevated levels of mRNA coding for proteins in glutathione synthesis/recycling, methionine reductase and redox system transcription factor pathways compared to larvae fed copepods.…”

“…Growth and other developmental processes are a balance between cellular proliferation, differentiation and apoptosis at both temporal and spatial levels [12]. For instance during larval fish ontogeny, cells undergo differentiation during organogenesis, proliferation during growth, and apoptosis when larval type tissue is replaced by adult type tissue [13][14][15].…”