Hypoxia impairs male reproductive functions via inducing rat Leydig cell ferroptosis under simulated environment at altitude of 5000 m.

AIMS: Many studies demonstrated reproductive damage in men residing in plains who are exposed to hypoxia at high altitudes. However, little is known about mechanisms between male reproductive impairment and hypobaric hypoxia. Hypoxia is one of the reasons for the imbalance of cellular redox system. Ferroptosis, involved in many pathophysiological progresses, is an oxidative damage-related, iron-dependent regulated cell death, which needs exogenous inducer. In our study, we explored the mechanism between hypoxia and male reproductive dysfunction. MATERIALS AND METHODS: Here, we established animal model simulating hypobaric hypoxia at an altitude of 5000 m and used ELISA, WB, qPCR, flow cytometry and etc. to obtain different results. KEY FINDINGS: The results demonstrated decrease of plasma testosterone (T) and free testosterone (FT) levels under hypoxia, meanwhile there's decline in sperm counts and sperm motility, coupled with increase in sperm malformation rates. Flow cytometry confirmed significant reduction in Leydig cell numbers. Prussian blue staining showed iron depositions in interstitial testis. Features of ferroptosis such as increased MDA (malondialdehyde) levels, reduced solute carrier family 7 member 11 (SLC7A11, xCT) and glutathione peroxidase 4 (GPX4) expression were observed in testis after hypoxic exposure. Further in vitro experiments, we observed that hypoxia suppressed xCT-GPX4 pathway and enhanced cellular ROS accumulation to lead Leydig cell proliferation activity decline. SIGNIFICANCE: Our findings firstly indicated that hypoxia leads to male reproductive dysfunction via inducing Leydig cell ferroptosis. This discovery may offer a potential intervention target for addressing male reproductive injuries under hypoxic conditions.

Vagal predominance correlates with mood state changes of winter-over expeditioners during prolonged Antarctic residence.

OBJECTIVE: Winter-over expeditioners in Antarctica are challenged by various environmental and psycho-social stress factors, which may induce psychophysiological changes. The autonomic nervous system (ANS) plays a crucial role in the adaptation process under stress. However, the relationship between ANS activity and the mood states of expeditioners remains largely unexplored. This study aims to uncover the pattern of ANS adjustment under extreme Antarctic environments and provide new insights into the correlations between ANS activity and mood state changes, which may provide scientific data for medical interventions. METHODS: Fourteen expeditioners at Zhongshan Station participated in this study. The study was conducted during four representative periods: pre-Antarctica, Antarctica-1 (pre-winter), Antarctica-2 (winter), and Antarctica-3 (summer). The heart rate variability (HRV) of the expeditioners was continuously measured for 24 hours to evaluate ANS activity. Plasma levels of catecholamines were tested by ELISA. Mood states were assessed by the Profile of Mood States (POMS) scale. RESULTS: HRV analysis showed a disturbance of ANS during winter and summer periods. For frequency domain parameters, very low frequency (VLF), low frequency (LF), high frequency (HF), and total power (TP) significantly increased during the second half of the mission. Especially, LF/HF ratio decreased during summer, indicating the predominance of vagal tone. Results of the time domain analysis showed increased heart rate variability during the austral winter and summer. Plasma epinephrine (E) significantly increased during residence in Antarctica. Compared with pre-Antarctica, the vigor, depression, and anger scores of the expeditioners decreased significantly during the austral summer. Notably, the depression score showed a moderate positive correlation with LF/HF, while weak negative correlations with other HRV indicators, including TP, VLF, and LF. Anger score showed a moderate positive correlation with LF/HF and weak negative correlations with the average normal-to-normal (NN) interval, and the root mean square of differences between adjacent RR intervals (RMSSD). Plasma E level weakly correlated with the average NN interval. CONCLUSION: Prolonged residence in Antarctica increased the ANS activities and shifted the cardiac autonomic modulation towards vagal predominance. The alteration of HRV correlated with mood states and plasma epinephrine levels.

Association of attenuated leptin signaling pathways with impaired cardiac function under prolonged high-altitude hypoxia.

Cardiovascular function and adipose metabolism were markedly influenced under high altitudes. However, the interplay between adipokines and heart under hypoxia remains to be elucidated. We aim to explore alterations of adipokines and underlying mechanisms in regulating cardiac function under high altitudes. We investigated the cardiopulmonary function and five adipokines in Antarctic expeditioners at Kunlun Station (4,087 m) for 20 days and established rats exposed to hypobaric hypoxia (5,000 m), simulating Kunlun Station. Antarctic expeditioners exhibited elevated heart rate, blood pressure, systemic vascular resistance, and decreased cardiac pumping function. Plasma creatine phosphokinase-MB (CK-MB) and platelet-endothelial cell adhesion molecule-1 (sPecam-1) increased, and leptin, resistin, and lipocalin-2 decreased. Plasma leptin significantly correlated with altered cardiac function indicators. Additionally, hypoxic rats manifested impaired left ventricular systolic and diastolic function, elevated plasma CK-MB and sPecam-1, and decreased plasma leptin. Chronic hypoxia for 14 days led to increased myocyte hypertrophy, fibrosis, apoptosis, and mitochondrial dysfunction, coupled with reduced protein levels of leptin signaling pathways in myocardial tissues. Cardiac transcriptome analysis revealed leptin was associated with downregulated genes involved in rhythm, Na+/K+ transport, and cell skeleton. In conclusion, chronic hypoxia significantly reduced leptin signaling pathways in cardiac tissues along with significant pathological changes, thus highlighting the pivotal role of leptin in regulation of cardiac function under high altitudes.

Neural Network Compression Based on Tensor Ring Decomposition.

Deep neural networks (DNNs) have made great breakthroughs and seen applications in many domains. However, the incomparable accuracy of DNNs is achieved with the cost of considerable memory consumption and high computational complexity, which restricts their deployment on conventional desktops and portable devices. To address this issue, low-rank factorization, which decomposes the neural network parameters into smaller sized matrices or tensors, has emerged as a promising technique for network compression. In this article, we propose leveraging the emerging tensor ring (TR) factorization to compress the neural network. We investigate the impact of both parameter tensor reshaping and TR decomposition (TRD) on the total number of compressed parameters. To achieve the maximal parameter compression, we propose an algorithm based on prime factorization that simultaneously identifies the optimal tensor reshaping and TRD. In addition, we discover that different execution orders of the core tensors result in varying computational complexities. To identify the optimal execution order, we construct a novel tree structure. Based on this structure, we propose a top-to-bottom splitting algorithm to schedule the execution of core tensors, thereby minimizing computational complexity. We have performed extensive experiments using three kinds of neural networks with three different datasets. The experimental results demonstrate that, compared with the three state-of-the-art algorithms for low-rank factorization, our algorithm can achieve better performance with much lower memory consumption and lower computational complexity.

Hypoxia promotes white adipose tissues browning in rats under simulated environment at altitude of 5000 m.

People living in plains tend to decrease in body weight or body fat percentage after entering the plateau. Previous studies have found that plateau animals can burn fat and release calories through white adipose tissues (WATs) browning. However, these studies have focused on the effect of cold stimulation that induced WATs browning while there's hardly study on the effect of hypoxia. In this study, we investigate that whether and how hypoxia contributes to WATs browning in rats from acute to chronic hypoxia. We constructed hypobaric hypoxic rat models by exposing 9-week-old male SD rats to a hypobaric hypoxic chamber for 1, 3, 14 and 28 days (Group H) under simulated environment at altitude of 5000 m. We also established normoxic control groups for each time period (Group C), as well as paired 1-day and 14-day normoxic food-restriction rats that were fed the same amount of food as the hypoxic group ate (Group R). We then observed the growth status of rats and recorded dynamic changes in histologic, cellular and molecular levels of perirenal WATs (PWAT), epididymal WATs (EWAT) and subcutaneous WATs (SWAT) in each group. Results showed that (1) Hypoxic rats had lower food intake, significantly lower body weight than control rats, and showed lower WATs index. (2) In group H14, ASC1 mRNA expressions of PWAT and EWAT in rats were lower than that in group C14, and PAT2 mRNA expression of EWAT was higher than that in both group C14 and R14. In group R14, however, ASC1 mRNA expressions of PWAT and EWAT in rats were higher than both group C14 and H14, and that of SWAT was also significantly higher than group C14. (3) In group H3, both the mRNA and protein levels of uncoupling protein 1 (UCP1) of PWAT in rats were significantly increased than group C3. And in group H14, those of EWAT in rats were significantly increased than group C14. (4) In plasma of rats, norepinephrine (NE) level was significantly increased in group H3 than group C3, and free fatty acids (FFAs) level was significantly increased in group H14 than both group C14 and R14. In group R1, FASN mRNA expressions of PWAT and EWAT in rats were down-regulated than group C1. In group H3, FASN mRNA expressions of PWAT and EWAT in rats were down-regulated while ATGL mRNA expression of EWAT was up-regulated than group C3. Conversely, in group R14, FASN mRNA expressions of PWAT and EWAT in rats were significantly up-regulated than group C14 and H14. These results suggested that hypoxia promoted different WATs browning in rats under simulated environment at altitude of 5000 m and changed the lipid metabolism in WATs. Furthermore, rats in the chronic hypoxic group showed a completely different lipid metabolism of WATs from that in paired food-restriction group.