Comprehensive Quantification of Oligoasthenozoospermia Induced by Obesity, Reproductive Toxicants, and Their Combination in Rat Models.

BACKGROUND

Oligoasthenozoospermia is a leading cause of male infertility and has been increasingly associated with the global surge in obesity and exposure to reproductive toxicants. Despite extensive research on each factor individually, their combined pathological effects remain poorly understood.

OBJECTIVES

This study aimed to investigate how obesity and reproductive toxicants independently and synergistically impair male reproductive function by establishing and comparing rat models of oligoasthenozoospermia induced by each factor and their combination.

MATERIALS AND

METHODS

We constructed three etiologically distinct oligoasthenozoospermia male Sprague-Dawley rat models: a reproductive toxicity model induced by glycosides of Tripterygium wilfordii Hook. f. (GTW), a metabolic dysfunction model induced by a high-fat diet (HFD), and a combined model (HFD + GTW). Animals were randomly assigned and subjected to 12 weeks of treatment. Body weight, metabolic indices, serum sex hormone levels, sperm quality parameters, and histopathological analysis of the testes and epididymis, as well as gut microbiota composition and testicular transcriptome profiles, were systematically evaluated. We also performed quantitative real-time polymerase chain reaction.

RESULTS

Both GTW and HFD independently impaired reproductive function, leading to decreased sperm count and motility, hormonal disturbances, and moderate testicular damage. The combined model exhibited significantly exacerbated reproductive impairment, including extensive spermatogenic cell loss, disrupted testicular architecture, and the lowest sperm quality indices. Multiomics analysis revealed coordinated alterations in gut microbiota composition and testicular transcriptomes, suggesting crosstalk between metabolic and inflammatory signaling pathways. Quantitative real-time polymerase chain reaction confirmed these transcriptomic patterns, showing upregulation of Ahnak, C1r, S1pr1, and Steap4, alongside downregulation of Alkbh7, Tbpl1, Tent5b, and Ldhal6b in the models.

CONCLUSION

This study successfully establishes reliable rat models that mimic both individual and combined etiologies of oligoasthenozoospermia. The interaction between obesity and GTW-induced reproductive toxicity aggravates testicular injury through metabolic disruption and inflammatory pathways, offering an integrative platform for mechanistic and therapeutic research.