Explore the Effect of Asthma Regulating HIF‐1 Pathway on Sperm Quality Based on Rat Model

Abstract

This study is to verify the effect of asthma on sperm quality and explore its potential underlying mechanism. We randomly categorized the Sprague-Dawley (SD) rats into control (Group C) and asthma model (Group M) groups. Rats in the asthma model group were induced allergic asthma by intraperitoneal injection of ovalbumin solution. We evaluated the sperm motility and sperm concentration. The expression of the Interleukin-6 (IL6), phosphorylation-signal transducer and activator of transcription 3 (p-Stat3), and hypoxia-inducible factor-1α (HIF-1α) proteins and mRNAs in the testicular tissue was detected by western blotting and RT-qPCR. Compared with group C, sperm concentration and sperm motility in group M rats were significantly decreased ( P < 0.05 ). Meanwhile, compared with group C, the expression levels of IL6, Stat3, and HIF-1α proteins and mRNAs in group M rats were significantly increased ( P < 0.05 ). Asthma can regulate the HIF-1 signaling pathway, promoting the expression of IL6, Stat3, and HIF-1α protein and mRNAs, so as to promote sperm apoptosis and ultimately causing male infertility.

Genetically predicted asthma and the risk of abnormal spermatozoa

“…Xu et al (2016) propose that asthma could activate the mitochondrial apoptosis signaling pathway in the mouse testis, thereby impacting spermatozoa quality. Similarly, Feng et al (2022) argue that asthma can modulate the HIF-1 signaling pathway, resulting in increased expression of IL6, Stat3, HIF-1α protein, and mRNA, ultimately leading to spermatozoa apoptosis. Additionally, Deng et al (2021) suggest that asthma can induce the production of abnormal spermatozoa by upregulating the expression of IL-6, vascular endothelial growth factor A, and mRNA while inhibiting albumin expression levels.…”

“…Our finding on the association between asthma and abnormal spermatozoa risk is consistent with previous studies. Recently, Multiple mouse model studies consistently indicate an association between asthma and spermatozoa quality, primarily characterized by significantly lower spermatozoa concentration and motility in the asthma mouse group compared to the control group ( Xu et al, 2016 ; Deng et al, 2021 ; Wang et al, 2021 ; Feng et al, 2022 ). Xu et al (2016) propose that asthma could activate the mitochondrial apoptosis signaling pathway in the mouse testis, thereby impacting spermatozoa quality.…”

“…It is characterized by a range of respiratory symptoms and airflow limitation to varied degrees, which can be generated by a range of airway inflammation and bronchospasm ( Papi et al, 2018 ). As illustrated in animal models, male mice with asthma were related to abnormal spermatozoa and testicular structure ( Xu et al, 2016 ; Deng et al, 2021 ; Wang et al, 2021 ; Feng et al, 2022 ). Moreover, a cross-sectional study in humans showed that men with asthma had lower spermatozoa concentration and total spermatozoa count compared with non-asthmatic men ( Pedersen et al, 2023 ).…”