Psychological stress (PS) disturbs the reproductive endocrine system and promotes male infertility, but the underlying pathogenic mechanisms have not been extensively studied. This study aimed to uncover the mechanisms of PS-induced male reproductive related abnormalities subjected to a ‘terrified sound’ exposure. Male rats subjected to PS displayed slow growth, decreased sperm quality, abnormal levels of the reproductive endocrine hormones, decreased expression of the reproductive-related proteins androgen-binding protein (ABP) and bromodomain-containing protein (BRDT), increased apoptosis in the testis, and accompanied by elevated levels of β-endorphin (β-EP). These effects were reversed by naloxone. Furthermore, PS-induced β-EP could promote mu opioid receptor (MOR) activation and ensure intracellular p38 MAPK phosphorylation and then lead to Leydig cells (LCs) apoptosis. The current result showed that β-EP was a key factor to PS-induced male infertility.
Stress is one of the leading causes of male infertility, but its exact function in testosterone synthesis has scarcely been reported. We found that adult male rats show a decrease in bodyweight, genital index and serum testosterone level after continual chronic stress for 21 days. Two‐dimensional gel electrophoresis (2‐DE) and MALDI‐TOF‐MS analysis identified 10 differentially expressed proteins in stressed rats compared with controls. A strong protein interaction network was found to be centred on Atp5a1 among these proteins. Atp5a1 expression significantly decreased in Leydig cells after chronic stress. Transfection of Atp5a1 siRNAs decreased StAR, CYP11A1, and 17β‐HSD expression by damaging the structure of mitochondria in TM3 cells. This study confirmed that chronic stress plays an important role in testosterone synthesis by regulating Atp5a1 expression in Leydig cells.
Purpose
Early diagnosis is crucial to improve outcomes for pancreatic cancer patients (PC). The present study is designed to identify differently expressed peptides involved in PC as potential biomarkers.
Experimental Design
The serum proteome of 22 PC patients, 12 pancreatitis patients (PP), and 45 healthy controls (HC) are analyzed using magnetic bead‐based weak cation exchange (MB‐WCX) and matrix‐assisted laser desorption ionization‐time of flight mass spectrometry (MALDI‐TOF MS). Next, a supervised neural network (SNN) algorithm model is established by ClinProTools and the candidate biomarker identified using liquid chromatography‐electrospray ionization‐tandem mass spectrometry (LC‐ESI‐MS/MS). Finally, the candidate biomarker is validated in tissue samples.
Results
The SNN algorithm model discriminates PC from HC with 92.97% sensitivity and 94.55% specificity. Seventy‐six differentially expressed peptides are identified, seven of which are significantly different among PC, PP, and HC (p < 0.05). Only one peak (m/z: 1466.99) tends to be upregulated in samples from HC, PP, and PC, which is identified as region of RNA‐binding motif protein 6 (RBM6). In subsequent tissue analysis, it is verified that RBM6 expression is significantly higher in PC tissues than paracancerous tissue.
Conclusions and Clinical Relevance
The results indicate that RBM6 might serve as a candidate diagnostic biomarker for PC.
Clinical Relevance
Methods used in this study could generate serum peptidome profiles of PC, PP, and HC, and present an approach to identify potential biomarkers for diagnosis of this malignancy.
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