Biological Network Model of Effect of Chronic Intermittent Hypoxia on Spermatogenesis in Rats

Abstract

Background The aim of this study was to explore the effect of obstructive sleep apnea hypopnea syndrome (OSAHS) on spermatogenesis and the effects of the expression of related proteins. Material/Methods Rats in Group A were normoxic (exposed to a normal level of oxygen). Rats in Group B were exposed to intermittent hypoxia. After 6 weeks, the rats were killed and their epididymides were removed. The epididymis of one testis was used to test indices of semen quality. The epididymis of the other testis was stained with hematoxylin & eosin to observe pathologic changes in the testis. We used real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting to measure expression of the protein and mRNA of leptin, Janus kinase (JAK), and signal transducer and activator of transcription (STAT) in rat testicular cells. Cytoscape v3.7.1 was employed to construct the OSAHS–male infertility network and protein–protein interactions network. Information on common targets of OSAHS and male infertility was imported into the Database for Annotation, Visualization and Integrated Discovery (DAVID). Then, analyses of pathway enrichment were undertaken using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Results Data were obtained 6 weeks after completion of OSAHS modeling. Compared with Group A, the total sperm count and sperm motility in Group B showed a downward trend (P<0.05). Staining showed no obvious abnormality in Group A. However, numerous structurally abnormal spermatogenic tubules were observed in Group B samples, and the lumen was atrophied and thinned, arranged unevenly, and the gap between the tubules was markedly increased. Western blotting and RT-qPCR showed that, compared with Group A, expression of the protein and mRNA of leptin, JAK, and STAT in the testes of rats in Group B was significantly increased (P<0.05 for all). Conclusions These data suggest that: (1) Chronic intermittent hypoxia can cause pathologic damage to rat testes; (2) Oligozoospermia was highly correlated and regulated by the JAK2/STAT6 signaling pathway; and (3) Chronic intermittent hypoxia can lead to decreased spermatogenesis in rats.

In vitro and in vivo investigation of the therapeutic mechanism of Lycium Chinense and Cuscutae Semen on oligoasthenozoospermia

“…To improve the reliability of the data obtained, each PPI was filtered further, with a minimum interaction score of 0.40. The filtered PPI was used for network construction and analyses (Wang, Gong, Deng, et al., 2020; Wang, Gong, Meng, et al, 2020).…”

“…The concept of network pharmacology is derived from the introduction of systems biology and the application of bioinformatics, as well as from the ‘omics’ theories related to the development of modern genomics, proteomics, and metabolomics. Based on the ‘disease‐gene‐target‐drug’ interaction network, a network analysis method was used to observe the intervention and influence of drugs on the disease network, and to determine the synergistic effect of multiple drugs (Wang, Gong, Deng, et al., 2020; Wang, Gong, Meng, et al, 2020). First, network pharmacology was used to predict key active ingredients and targets.…”

Effects of Environmental and Pathological Hypoxia on Male Fertility

“…The sperm quality outcome measures are the sperm concentration, motility, morphology, semen volume, viability and DNA fragmentation, which are the parameters most frequently used in clinical settings ( Schisterman et al, 2020 ). Growing evidence has shown that hypoxia has adverse effects on sperm quality in several species, including rodents, livestock, Drosophila, fish, and humans ( Wang et al, 2016 ; Cofre et al, 2018 ; Wang J. et al, 2020 ). In rats and mice, acute, intermittent and chronic hypoxia reduced the total sperm concentration and sperm motility while increasing the rates of sperm DNA fragmentation and abnormal sperm morphology ( Vargas et al, 2011 ; Torres et al, 2014 ; Bai et al, 2018 ; Wang J. et al, 2020 ; Ma et al, 2021 ).…”

“…Growing evidence has shown that hypoxia has adverse effects on sperm quality in several species, including rodents, livestock, Drosophila, fish, and humans ( Wang et al, 2016 ; Cofre et al, 2018 ; Wang J. et al, 2020 ). In rats and mice, acute, intermittent and chronic hypoxia reduced the total sperm concentration and sperm motility while increasing the rates of sperm DNA fragmentation and abnormal sperm morphology ( Vargas et al, 2011 ; Torres et al, 2014 ; Bai et al, 2018 ; Wang J. et al, 2020 ; Ma et al, 2021 ). Hypoxia in rams led to a lower sperm count, sperm progressive motility and viability than in normoxic rams ( Cofre et al, 2018 ).…”

“…The former mainly refers to low partial pressure of inhaled oxygen caused by high altitude, while the latter is impaired testicular oxygen delivery or utilization caused by pathological factors, including varicocele ( Jensen et al, 2017 ), chronic lung disease ( Semple et al, 1983 ), sleep apnea ( Mesarwi et al, 2019 ) and sickle cell disease ( Torres et al, 2014 ). Both environmental and pathological hypoxia have been shown to negatively affect male fertility in animals and humans, which can lead to a reduced sperm count, low sperm motility and abnormal sperm morphology on sperm output ( Ata-Abadi et al, 2020 ; Wang J. et al, 2020 ). However, the adverse consequences of hypoxia on male fertility have been established in some studies, but it is difficult to make a firm conclusion without enough evidence.…”