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Multi-Omics Analysis Reveals Molecular Disruption in Mouse Testes Following Cumulative heat stress

ABSTRACT: Rising global temperatures threaten male fertility, yet the molecular mechanisms by which heat stress disrupts spermatogenesis remain incompletely understood. We employed an integrative multi-omics approach incorporating transcriptomics, proteomics, and metabolomics to examine the impact of sub-lethal HS (Heat stress) on the testes and spermatozoa of male mice. Our results demonstrated that HS significantly diminished sperm motility and compromised the architecture of seminiferous tubules. Multi-omics integration demonstrated a synchronized downregulation of pathways regulating glycolysis, flagellar assembly, and antioxidant defense, as well as disruptions in steroid hormone production and redox equilibrium. These systemic changes collectively contribute to defective energy metabolism, aberrant sperm viability, and diminished tolerance to oxidative stress, ultimately leading to reduced reproductive potential. This study provides an integrated multi-omics view of heat stress–associated molecular disruptions in mouse testes and highlights convergent pathways linked to impaired male reproductive function

ORGANISM(S): Mus Musculus

SUBMITTER: Guozhi Yu

PROVIDER: PXD074923 | iProX | Thu Feb 26 00:00:00 GMT 2026

REPOSITORIES: iProX

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Multi-omics analysis reveals molecular disruption in mouse testes following cumulative heat stress.

Baibrus Muhammad Ammar MA Nazir Farwa F Zhou Run R Xiong Hao H Liang Qiuxia Q Huang Anqi A Majeed Adnan A Zhou Guangbin G Yu Guozhi G

Comparative biochemistry and physiology. Part D, Genomics & proteomics 20260303

Rising global temperatures threaten male fertility, yet the molecular mechanisms by which heat stress disrupts spermatogenesis remain incompletely understood. We employed an integrative multi-omics approach incorporating transcriptomics, proteomics, and metabolomics to examine the impact of sub-lethal HS (Heat stress) on the testes and spermatozoa of male mice. Our results demonstrated that HS significantly diminished sperm motility and compromised the architecture of seminiferous tubules. Multi ...[more]

PMID: 41795304

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Project description:BACKGROUND: Large-scale farms struggle to effectively address summer heat stress (HS) in dairy goats, which impairs spermatogenesis and reduces reproductive performance by compromising gut and reproductive organ health in male animals. Although Clostridium butyricum (CB) and Enterococcus faecium (EF) have been used to alleviate gut dysbiosis, their protective effects and mechanisms against HS-induced spermatogenic dysfunction in dairy goats remain unclear. This study aims to evaluate the efficacy of CB and EF in mitigating HS-induced spermatogenic disorders in male dairy goats and elucidate the underlying mechanisms.RESULTS: HS leads to a significant decline in sperm quality. CB and EF ameliorate HS-induced sperm quality deterioration by reducing pro-inflammatory factors and oxidative stress levels in blood, while modulating the disrupted reproductive hormone levels caused by heat stress. 16S rRNA-based microbiota analysis revealed that CB and EF treatment shifted the gut microbiota of HS-treated male dairy goats toward a composition resembling that of the NC. To investigate whether the protective effects of these probiotics on sperm quality are mediated through gut microbiota modulation, we transplanted fecal microbiota from HS-treated dairy goats (with or without probiotic intervention) into antibiotic-induced microbiome-depleted (AIMD) mice, followed by heat stress exposure. We observed severe testicular damage and spermatogenic impairment in mice receiving HS group microbiota, whereas these pathological manifestations were significantly alleviated in mice receiving microbiota from probiotic-treated HS goats, indicating that CB and EF mitigate HS-induced spermatogenic damage in a microbiota-dependent manner. Furthermore, non-targeted metabolomics sequencing identified significant reductions in arginine (Arg) and pantothenic acid (PaA) levels in both HS-treated goats and HS microbiota-transplanted mice, metabolites that showed correlation with sperm quality parameters. Subsequent studies demonstrated that supplementation with Arg and PaA effectively attenuated the elevation of pro-inflammatory factors and oxidative stress in mouse blood, restored intercellular junctions, and ultimately ameliorated spermatogenic disorders.CONCLUSION: This study demonstrates that CB and EF alleviate HS-induced sperm quality decline in dairy goats by modulating the gut microbiota to increase blood levels of Arg and PaA. These findings highlight novel therapeutic avenues for preventing HS-induced spermatogenic disorders in dairy goats and provide fresh insights into the application of probiotics to mitigate heat stress-associated impairments in sperm production.

Project description:Background: Heat stress is an increasing global health concern associated with high mortality and multi-organ dysfunction. The brain is particularly vulnerable, leading to behavioral impairments. At the molecular level, heat stress disrupts proteins involved in synaptic communication, mitochondrial function, and cellular homeostasis. Current treatments are mainly symptomatic, highlighting the need for targeted neuroprotective strategies. Edaravone, a potent free-radical scavenger with anti-inflammatory properties, has demonstrated neuroprotective effects in various neurological conditions. This study aimed to evaluate the neuroprotective effects of edaravone against heat stress–induced behavioral dysfunction and to investigate the underlying molecular mechanisms using proteomic analysis. Methodology: Male Wistar rats (n = 54) were assigned to four groups: control, heat stress (HS), edaravone (Edv), and heat stress plus edaravone (HS+Edv). Heat stress and treatment were administered for 12 weeks. Behavioral assessments, including radial arm water maze (RAWM), open field test (OFT), elevated plus maze (EPM), and tail suspension test (TST), were conducted. Proteomic analysis of the cortex, hippocampus, and cerebellum was performed using UHPLC–QTOF-MS. Result: Heat stress induced significant impairments in memory, learning, anxiety-like, and depressive-like behaviors. Proteomic analysis revealed region-specific alterations, with the cerebral cortex showing the most pronounced changes, particularly in pathways related to mitochondrial function, oxidative stress, synaptic signaling, and protein quality control. The HS+Edv group showed partial normalization of behavioral outcomes and modulation of key proteomic pathways, including improved mitochondrial function, reduced oxidative stress, and preservation of synaptic and cytoskeletal integrity. Conclusion: Edaravone attenuates heat stress–induced brain dysfunction by promoting adaptive proteomic remodeling rather than complete restoration.

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Multi-Omics Analysis Reveals Molecular Disruption in Mouse Testes Following Cumulative heat stress

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Multi-omics analysis reveals molecular disruption in mouse testes following cumulative heat stress.

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