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Despite extensive research on each factor individually, their combined pathological effects remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      We constructed three etiologically distinct oligoasthenozoospermia male Sprague\u2013Dawley rat models: a reproductive toxicity model induced by glycosides of\n                      <jats:italic>Tripterygium wilfordii<\/jats:italic>\n                      Hook. f. (GTW), a metabolic dysfunction model induced by a high\u2010fat 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\u2010time polymerase chain reaction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\u2010time polymerase chain reaction confirmed these transcriptomic patterns, showing upregulation of\n                      <jats:italic>Ahnak<\/jats:italic>\n                      ,\n                      <jats:italic>C1r<\/jats:italic>\n                      ,\n                      <jats:italic>S1pr1<\/jats:italic>\n                      , and\n                      <jats:italic>Steap4<\/jats:italic>\n                      , alongside downregulation of\n                      <jats:italic>Alkbh7<\/jats:italic>\n                      ,\n                      <jats:italic>Tbpl1<\/jats:italic>\n                      ,\n                      <jats:italic>Tent5b<\/jats:italic>\n                      , and\n                      <jats:italic>Ldhal6b<\/jats:italic>\n                      in the models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study successfully establishes reliable rat models that mimic both individual and combined etiologies of oligoasthenozoospermia. The interaction between obesity and GTW\u2010induced reproductive toxicity aggravates testicular injury through metabolic disruption and inflammatory pathways, offering an integrative platform for mechanistic and therapeutic research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70171","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:41:59Z","timestamp":1769161319000},"page":"1535-1551","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive Quantification of Oligoasthenozoospermia Induced by Obesity, Reproductive Toxicants, and Their Combination in Rat Models"],"prefix":"10.1111","volume":"14","author":[{"given":"Yunlong","family":"Yao","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine Beijing University of Chinese Medicine  Beijing China"},{"name":"National Institute of Traditional Chinese Medicine Constitution and 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