The consumption of energy-dense diets has contributed to an increase in the prevalence of obesity and its comorbidities worldwide. The adoption of unhealthy feeding habits often occurs at early age, ...prompting the early onset of metabolic disease with unknown consequences for reproductive function later in life. Recently, evidence has emerged regarding the intergenerational and transgenerational effects of high-fat diets (HFD) on sperm parameters and testicular metabolism. Hereby, we study the impact of high-fat feeding male mice (F
) on the testicular metabolome and function of their sons (F
) and grandsons (F
). Testicular content of metabolites related to insulin resistance, cell membrane remodeling, nutritional support and antioxidative stress (leucine, acetate, glycine, glutamine, inosine) were altered in sons and grandsons of mice fed with HFD, comparing to descendants of chow-fed mice. Sperm counts were lower in the grandsons of mice fed with HFD, even if transient. Sperm quality was correlated to testicular metabolite content in all generations. Principal Component Analysis of sperm parameters and testicular metabolites revealed an HFD-related phenotype, especially in the diet-challenged generation and their grandsons. Ancestral HFD, even if transient, causes transgenerational "inherited metabolic memory" in the testicular tissue, characterized by changes in testicular metabolome and function.
Parenthood at an older age is becoming a trend among men, especially in the most developed societies. Aging has a significant impact on male fertility. Older men exhibit notable disturbances in the ...reproductive axis, with steroidogenesis being impacted much more than spermatogenesis. The endocrine changes, together with morphological and functional alternations of the aging testis, result in decreased testosterone production. Nonetheless, studies are needed to scrutinize the impact of age per se versus age-induced dysfunction of the reproductive axis. Furthermore, the multiple effects of aging on the acquisition of sperm motility, on sperm morphology and concentration indicate that the quality of spermatozoa declines over time, but few works have shed light on the molecular mechanisms that hamper sperm function in old men. In fact, this question is far from being completely answered and this is a subject of controversy. Hence, we will present an up-to-date review and discuss the molecular mechanisms involved in the alteration of the reproductive function in aging men. We will focus on the functioning of the reproductive axis and what are the major effects of aging in spermatogenesis. We will also discuss how aging affects sperm quality and possible causes underlying sperm dysfunction with special emphasis in oxidative stress.
Hormonal regulation is essential to spermatogenesis. Sertoli cells (SCs) have functions that reach far beyond the physical support of germ cells, as they are responsible for creating the adequate ...ionic and metabolic environment for germ cell development. Thus, much attention has been given to the metabolic functioning of SCs. During spermatogenesis, germ cells are provided with suitable metabolic substrates, in a set of events mediated by SCs. Multiple signaling cascades regulate SC function and several of these signaling pathways are hormone-dependent and cell-specific. Within the seminiferous tubules, only SCs possess receptors for some hormones rendering them major targets for the hormonal signaling that regulates spermatogenesis. Although the mechanisms by which SCs fulfill their own and germ cells metabolic needs are mostly studied in vitro, SC metabolism is unquestionably a regulation point for germ cell development and the hormonal control of these processes is required for a normal spermatogenesis.
Male factor infertility is increasing in developed countries, and several factors linked to lifestyle have been shown to negatively affect spermatogenesis. Sertoli cells are pivotal to ...spermatogenesis, providing nutritional support to germ cells throughout their development. Sertoli cells display atypical features in their cellular metabolism; they can metabolize various substrates, preferentially glucose, the majority of which is converted to lactate and not oxidized via the tricarboxylic acid cycle. Why Sertoli cells preferentially export lactate for germ cells is not entirely understood. However, lactate is utilized as the main energy substrate by developing germ cells and has an antiapoptotic effect on these cells. Several biochemical mechanisms contribute to the modulation of lactate secretion by Sertoli cells. These include the transport of glucose through the plasma membrane, mediated by glucose transporters; the interconversion of pyruvate to lactate by lactate dehydrogenase; and the release of lactate mediated by monocarboxylate transporters. Several factors that modulate Sertoli cell metabolism have been identified, including sex steroid hormones, which are crucial for maintenance of energy homeostasis, influencing the metabolic balance of the whole body. In fact, energy status is essential for normal reproductive function, since the reproductive axis has the capacity to respond to metabolic cues.
Over the years, due to the enrichment of paired-label datasets, supervised machine learning has become a prime component of any problem-solving. Examples include building classifiers for applications ...such as image/speech recognition, traffic prediction, product recommendation, virtual personal assistant (VPA), online fraud detection and many more. The performance of these developed classifiers is highly dependent upon the training dataset, and subsequently, without human intervention or true labels, the evaluation over unseen observations remains unknown. Using a statistical distance researchers did try to assess the model's goodness-of-fit and compared multiple independent models. Nonetheless, given a train-test split and different classifiers built over the training set, the question 'is it possible to find a prediction error using the relation between training and test set?' remains unsolved. In this article, we propose a generalized statistical distance-based method measuring the prediction uncertainty at a new query point. To be specific, we propose a Mahalanobis distance-based Evidence Function Model to measure the misclassification caused by K-Nearest Neighbours (KNN), Extra Trees (ET), and Convolutional Neural Network (CNN) models when classifying Sentinel-2 image into six scene classes (Water, Shadow, Cirrus, Cloud, Snow, Other). The performance of the proposed method was assessed over two different datasets: (i) the test set, with an overall mean prediction uncertainty detection of 62.99%, 29.80% and 31.51%, leading to a mean micro-F1 performance of 67.89%, 39.30%, and 38.29% for KNN, ET, and CNN, respectively; (ii) a water-body set, with prediction uncertainty detection of 22.27%, 42.08%, and 27.67%, leading to a micro-F1 performance of 34.70%, 58.96%, and 43.32%, respectively.
Obesogens have been identified as a significant factor associated with increasing obesity rates, particularly in developed countries. Substances with obesogenic traits are prevalent in consumer ...products, including certain pharmaceuticals. Specific classes of pharmaceuticals have been recognized for their ability to induce weight gain, often accompanied by hormonal alterations that can adversely impact male fertility. Indeed, research has supplied evidence underscoring the crucial role of obesogens and therapeutic agents in the normal functioning of the male reproductive system. Notably, sperm count and various semen parameters have been closely linked to a range of environmental and nutritional factors, including chemicals and pharmacological agents exhibiting obesogenic properties. This review aimed to explore studies focused on analyzing male fertility parameters, delving into the intricacies of sperm quality, and elucidating the direct and adverse effects that pharmacological agents may have on these aspects.
Given the continuous increase in the global population, the food manufacturers are advocated to either intensify the use of cropland or expand the farmland, making land cover and land usage dynamics ...mapping vital in the area of remote sensing. In this regard, identifying and classifying a high-resolution satellite imagery scene is a prime challenge. Several approaches have been proposed either by using static rule-based thresholds (with limitation of diversity) or neural network (with data-dependent limitations). This paper adopts the inductive approach to learning from surface reflectances. A manually labeled Sentinel-2 dataset was used to build a Machine Learning (ML) model for scene classification, distinguishing six classes (Water, Shadow, Cirrus, Cloud, Snow, and Other). This models was accessed and further compared to the European Space Agency (ESA) Sen2Cor package. The proposed ML model presents a Micro-F1 value of 0.84, a considerable improvement when compared to the Sen2Cor corresponding performance of 0.59. Focusing on the problem of optical satellite image scene classification, the main research contributions of this paper are: (a) an extended manually labeled Sentinel-2 database adding surface reflectance values to an existing dataset; (b) an ensemble-based and a Neural-Network-based ML models; (c) an evaluation of model sensitivity, biasness, and diverse ability in classifying multiple classes over different geographic Sentinel-2 imagery, and finally, (d) the benchmarking of the ML approach against the Sen2Cor package.
Prediabetes (PrDM) is a prodromal stage of diabetes mellitus (DM) with an increasing prevalence worldwide. During DM progression, individuals gradually develop complications in various organs. ...However, lungs are suggested to be affected later than other organs, such as the eyes, heart or brain. In this work, we studied the effects of PrDM on male Wistar rats’ lungs and whether the regular consumption of white tea (WTEA) for 2 months contributes to the improvement of the antioxidant profile of this tissue, namely through improved activity of the first line defense antioxidant enzymes, the total antioxidant capacity and the damages caused in proteins, lipids and histone H2A. Our data shows that PrDM induced a decrease in lung superoxide dismutase and glutathione peroxidase activities and histone H2A levels and an increase in protein nitration and lipid peroxidation. Remarkably, the regular WTEA intake improved lung antioxidant enzymes activity and total antioxidant capacity and re-established the values of protein nitration, lipid peroxidation and histone H2A. Overall, this is the first time that lung is reported as a major target for PrDM. Moreover, it is also the first report showing that WTEA possesses relevant chemical properties against PrDM-induced lung dysfunction.
The digital world is very dynamic. The ability to timely identify possible vendor migration trends or customer loss risks is very important in cloud-based services. This work describes a churn risk ...prediction system and how it can be applied to guide cloud service providers for recommending adjustments in the service subscription level, both to promote rational resource consumption and to avoid CSP customer loss. A training dataset was built from real data about the customer, the subscribed service and its usage history, and it was used in a supervised machine-learning approach for prediction. Classification models were built and evaluated based on multilayer neural networks, AdaBoost and random forest algorithms. From the experiments with our dataset, the best results for a churn prediction were obtained with a random forest-based model, with 64 estimators, having 0.988 accuracy and 0.997 AUC value.
Childhood obesity is a serious concern associated with ill health later in life. Emerging data suggest that obesity has long-term adverse effects upon male sexual and reproductive health, but few ...studies have addressed this issue. We hypothesized that exposure to high-fat diet during early life alters testicular lipid content and metabolism, leading to permanent damage to sperm parameters. After weaning (
after birth), 36 male mice were randomly divided into three groups and fed with a different diet regimen for 200 days: a standard chow diet (CTRL), a high-fat diet (HFD) (carbohydrate: 35.7%, protein: 20.5%, and fat: 36.0%), and a high-fat diet for 60 days, then replaced by standard chow (HFD
). Biometric and metabolic data were monitored. Animals were then euthanized, and tissues were collected. Epididymal sperm parameters and endocrine parameters were evaluated. Testicular metabolites were extracted and characterized by 1H-NMR and GC-MS. Testicular mitochondrial and antioxidant activity were evaluated. Our results show that mice fed with a high-fat diet, even if only until early adulthood, had lower sperm viability and motility, and higher incidence of head and tail defects. Although diet reversion with weight loss during adulthood prevents the progression of metabolic syndrome, testicular content in fatty acids is irreversibly affected. Excessive fat intake promoted an overaccumulation of proinflammatory n-6 polyunsaturated fatty acids in the testis, which is strongly correlated with negative effects upon sperm quality. Therefore, the adoption of high-fat diets during early life correlates with irreversible changes in testicular lipid content and metabolism, which are related to permanent damage to sperm quality later in life.
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