2. Universidad Cardenal Herrera-CEU

Autophagy is a fine-tuned proteolytic pathway that moves dysfunctional/aged cellular components into the lysosomal compartment for degradation. Over the last 3 decades, global research has provided evidence for the protective role of autophagy in different brain cell components. Autophagic capacities decline with age, which contributes to the accumulation of obsolete/damaged organelles and proteins and, ultimately, leads to cellular aging in brain tissues. It is thus well-accepted that autophagy plays an essential role in brain homeostasis, and malfunction of this catabolic system is associated with major neurodegenerative disorders. Autophagy function can be modulated by different types of stress, including glycative stress. Glycative stress is defined as a cellular status with abnormal and accelerated accumulation of advanced glycation end products (AGEs). It occurs in hyperglycemic states, both through the consumption of high-sugar diets or under metabolic conditions such as diabetes. In recent years, glycative stress has gained attention for its adverse impact on brain pathology. This is because glycative stress stimulates insoluble, proteinaceous aggregation that is linked to the malfunction of different neuropathological proteins. Despite the emergence of new literature suggesting that autophagy plays a major role in fighting glycation-derived damage by removing cytosolic AGEs, excessive glycative stress might also negatively impact autophagic function. In this mini-review, we provide insight on the status of present knowledge regarding the role of autophagy in brain physiology and pathophysiology, with an emphasis on the cytoprotective role of autophagic function to ameliorate the adverse effects of glycation-derived damage in neurons, glia, and neuron-glia interactions.

Embryo implantation is a complex process in which significant changes occur continually in both the corpora lutea and in the endometrium of females and which varies depending on the embryonic, pre-implantation, or fetal stages. However, at all stages, correct maternal–embryonic communication is essential. In the last few years, a new intercellular communication tool, mediated by extracellular vesicles (EVs), has emerged. Many authors agree on the relevant role of EVs in correct communication between the mother and the embryo, as a fundamental system for the pregnancy to reach term and embryonic development to occur correctly. This review analyzes current information on known EVs, their main functions, and their role in implantation and embryonic development in domestic animals.

The regulation of early events in mammalian embryonic development is a complex process. In the early stages, pluripotency, cellular differentiation, and growth should occur at specific times and these events are regulated by different genes that are expressed at specific times and locations. The genes related to pluripotency and cellular differentiation, and growth factors that determine successful embryonic development are different (or differentially expressed) among mammalian species. Some genes are fundamental for controlling pluripotency in some species but less fundamental in others, for example, Oct4 is particularly relevant in bovine early embryonic development, whereas Oct4 inhibition does not affect ovine early embryonic development. In addition, some mechanisms that regulate cellular differentiation do not seem to be clear or evolutionarily conserved. After cellular differentiation, growth factors are relevant in early development, and their effects also differ among species, for example, insulin-like growth factor improves the blastocyst development rate in some species but does not have the same effect in mice. Some growth factors influence genes related to pluripotency, and therefore, their role in early embryo development is not limited to cell growth but could also involve the earliest stages of development. In this review, we summarize the differences among mammalian species regarding the regulation of pluripotency, cellular differentiation, and growth factors in the early stages of embryonic development.

We tested whether periconceptional nutrition with cladodes from the cactus, Opuntia ficus-indica, with or without protein-enrichment, improved the metabolomic profile and reproductive outcomes of adult female sheep. Sixty Rambouillet ewes of similar body weight were randomly allocated among three nutritional treatments that were fed during the breeding period (34 days): Control (Control; n = 20), Opuntia (Opuntia; n = 20) and protein-enriched Opuntia (E-Opuntia; n = 20). There were no effects of treatment on body weight but assessment of urine samples indicated that, for 76 metabolites, the Control and Opuntia groups differed completely (P < 0.05), whereas there was overlap between the Control and E-Opuntia groups. It appears that, in Opuntia-fed and Control-fed sheep, different functional groups are activated leading to changes in the metabolism of glucose, tyrosine, methane, and glycerolipids. Fertility and reproductive rate tended to be higher in the Opuntia (70% and 95%) and E-Opuntia (90% and 110%) groups than in the Control (55% and 65%), and an orthogonal contrast revealed the difference between Control and Opuntia to be significant for both reproductive variables (P < 0.05). We conclude that nutritional supplementation with Opuntia cladodes, with or without protein enrichment, increased fertility rate and reproductive rate of female sheep, without any accompanying increases in body weight. Our observations suggest that the reproductive responses to Opuntia do not simply reflect a response to good nutrition, but might be caused by specific metabolites/metabolomic pathways, perhaps by an activation of the metabolism of glucose, methane, tyrosine and glycerolipids. There are few reports relating these metabolomic compounds with the metabolism of the sheep, let alone with reproductive efficiency. The novelty of these discoveries suggests that we need further research into the mechanisms through which nutrition affects the reproductive system.