Non-obstructive azoospermia (NOA) is one of the most important causes of male infertility. Although many congenital factors have been identified, the aetiology in the majority of idiopathic NOA (iNOA) cases remains unknown. Herein, using single-cell RNA-Seq data sets (GSE149512) from the Gene Expression Omnibus (GEO) database, we constructed transcriptional regulatory networks (TRNs) to explain the mutual regulatory relationship and the causal relationship between transcription factors (TFs). We defined 10 testicular cell types by their marker genes and found that the proportion of Leydig cells (LCs) and macrophages (tMΦ) was significantly increased in iNOA testis. We identified specific TFs including LHX9, KLF8, KLF4, ARID5B and RXRG in iNOA LCs. In addition, we found specific TFs in iNOA tMΦ such as POU2F2, SPIB IRF5, CEBPA, ELK4 and KLF6. All these identified TFs are strongly engaged in cellular fate, function and homeostasis of the microenvironment. Changes in the activity of the above-mentioned TFs might affect the function of LCs and tMΦ and ultimately cause spermatogenesis failure. This study illustrate that these TFs play important regulatory roles in the occurrence and development of NOA.
Limited knowledge of the long‐term effects of excessive iodine (EI) intake on biomolecular signatures in the liver/pancreas/kidney prompted this study. Herein, following 6 months of exposure in mice to 300, 600, 1200 or 2400 μg/L iodine, the biochemical signature of alterations to the liver/pancreas/kidney was profiled using attenuated total reflection Fourier‐transform infrared (ATR‐FTIR) spectroscopy coupled with principal component analysis‐linear discriminant analysis (PCA‐LDA). Our research showed that serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (Scr), insulin, blood glucose levels and homeostasis model assessment for insulin resistance (HOMA‐IR) index in the 1200 and 2400 μg/L iodine‐treated groups were significantly increased compared with those in the control group. Moreover, histological analysis showed that the liver/kidney/pancreas tissues of mice exposed to EI treatment displayed substantial morphological abnormalities, such as a loss of hepatic architecture, glomerular cell vacuolation and pancreatic neutrophilic infiltration. Notably, EI treatment caused distinct biochemical signature segregation between EI‐exposed versus the control liver/pancreas/kidney. The main biochemical alterations between EI‐exposed and control groups were observed for protein phosphorylation, protein secondary structures and lipids. The ratios of amide I‐to‐amide II (1674 cm−1/1570 cm−1), α‐helix‐to‐β‐sheet (1657 cm−1/1635 cm−1), glycogen‐to‐phosphate (1030 cm−1/1086 cm−1) and the peptide aggregation (1 630 cm−1/1650 cm−1) level of EI‐treated groups significantly differed from the control group. Our study demonstrated that EI induced hepatic, renal and pancreatic injury by disturbing the structure, metabolism and function of the cell membrane. This finding provides the new method and implication for human health assessment regarding long‐term EI intake.
Asthenozoospermia is a common form of abnormal sperm quality in idiopathic male infertility. While most sperm-mediated causes have been investigated in detail, the significance of seminal plasma has been neglected. Herein, we aimed to investigate the possible pathogenic factors leading to decreased sperm motility based on seminal plasma. Semen was collected from normo- (NOR, n = 70 ), idiopathic oligo- (OLI, n = 57 ), and idiopathic asthenozoospermic (AST, n = 53 ) patients. Using attenuated total reflection-Fourier transform infrared coupled with chemometrics, distinct differences in the biochemical compositions of nucleic acids, protein structure (amides I, II, and III), lipids, and carbohydrates in seminal plasma of AST were observed when compared to NOR and OLI. Compared with NOR and OLI, the levels of peptide aggregation, protein phosphorylation, unsaturated fatty acid, and lipid to protein ratio were significantly increased in AST; however, the level of lipid saturation was significantly decreased in seminal plasma of AST. Compared with NOR, the levels of ROS, MDA, 8-iso-prostaglandin F2α (8-isoPGF2α), and the ratio of phospho-AMPKα/AMPKα1 were significantly increased in AST; however, the levels of SOD, glutathione S-transferase (GSTs), protein carbonyl derivative (PC), and the ratio of phospho-Rictor/Rictor were significantly decreased in seminal plasma of AST. Changes of the AMPK/mTORC2 signaling in the seminal microenvironment possibly induce abnormal glucose and lipid metabolism, which impairs energy production. Oxidative stress potentially damages seminal plasma lipids and proteins, which in turn leads to impaired sperm structure and function. These findings provide evidence that the changes in seminal plasma compositions, oxidative stress, and activation of the AMPK/mTORC2 signaling contribute to the development of asthenozoospermia.
Bisphenol A (BPA) and 4-nonylphenol (NP) are well-known endocrine-disrupting chemicals (EDCs) that have been proven to affect Leydig cell (LC) functions and testosterone production, but whether BPA and NP have multi-and transgenerational biochemical effects on Leydig cells (LCs) is unknown. Fourier transform infrared (FTIR) spectroscopy is a powerful analytical technique that enables label-free and non-destructive analysis of the tissue specimen. Herein we employed FTIR coupled with chemometrics analysis to identify biomolecular changes in testicular interstitial (Leydig) cells of rats after chronic exposure to low doses of BPA and NP. Cluster segregations between exposed and control groups were observed based on the fingerprint region of 1800-900 cm À1 in all generations. The main biochemical alterations for segregation were amide I, amide II and nucleic acids. BPA and NP single and coexposure induced significant differences in the ratio of amide I to amide II compared to the corresponding control group in all generations. BPA exposure resulted in remarkable changes of cellular gene transcription and DNA oxidative damage across all generations. Direct exposure to BPA, NP, and BPA&NP of F0 and F1 generations could significantly decrease lipid accumulation in LCs in the F2 and F3 generations.The overall findings revealed that single or co-exposure to BPA and NP at environmental concentrations affects the biochemical structures and properties of LCs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.