Response of the mTOR signaling pathway to the reproductive dysfunction of dysbiosis-induced male mice

Apr 2, 2026Reproductive biology

mTOR signaling changes linked to reproductive problems in male mice with gut imbalance

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Abstract

Serum sex hormone levels significantly decreased in antibiotic-induced dysbiosis mice.

Glucose levels were significantly lower in serum from dysbiosis mice compared to controls (p < 0.05).
Cholesterol levels were significantly elevated in the serum of dysbiosis mice (p < 0.05).
Pro-inflammatory cytokines IL-1β, IL-6, and TNF-α showed significant increases in the testis of the dysbiosis group (p < 0.05 & p < 0.01).
Expression of testosterone synthesis genes, including 3β-HSD and P450scc, significantly decreased in dysbiosis mice (p < 0.05).
The mTOR signaling pathway components were significantly upregulated in the testis of dysbiosis mice (p < 0.05).
Increased pro-inflammatory cytokine secretion and impaired sperm quality could be linked to dysregulated mTOR signaling.

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The mammalian target of rapamycin (mTOR) signaling pathway plays a key role in coordinating several cellular activities in response to environmental signals, thereby influencing metabolism and reproduction. This study aimed to determine the role of mTOR signaling pathway in testicular dysfunction caused by intestinal microbiome imbalance. An antibiotic mixture containing ampicillin, neomycin sulfate, vancomycin, and metronidazole was administered orally to mice for four weeks, and subsequently serum, and tissues were obtained following sacrifice. Glucose, cholesterol, and sex hormone levels were measured in the serum, and real-time PCR was performed using extracts of the ileum and testis to determine the expression of genes associated with pro-inflammatory cytokines, mTOR signals and testosterone synthesis. The levels of glucose and sex hormones in the serum of antibiotic-induced dysbiosis (WD) mice were significantly decreased, while the cholesterol levels were elevated (p < 0.05). The mRNA expression of IL-1β, IL-6 and TNF-α significantly increased in the testis of the WD group (p < 0.05 & p < 0.01), while testosterone synthesis, such as the expression of 3β-HSD and P450scc decreased (p < 0.05). Immunofluorescence revealed the localization of mTOR in the mid-piece and tail of the epididymal spermatozoa. The mRNA expression of mTOR signaling pathway, including Mtor, Raptor, p53, PI3K, Akt1, P70s6k, and Rheb, was significantly upregulated in the testis of the WD group (p < 0.05). Consequently, antibiotic-induced dysbiosis in male mice led to increased secretion of pro-inflammatory cytokines in the testis, decreased serum sex hormone levels, and impaired sperm quality, all of which could be associated with altered regulation of the mTOR signaling pathway.

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Response of the mTOR signaling pathway to the reproductive dysfunction of dysbiosis-induced male mice

Abstract

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