{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:19:05Z","timestamp":1790291945981,"version":"4.1.0"},"reference-count":68,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Liaoning Science Planning Project, the Educational Department of Liaoning Province","award":["LSNJC202009"],"award-info":[{"award-number":["LSNJC202009"]}]},{"name":"Liaoning Science Planning Project, the Educational Department of Liaoning Province","award":["LSNFW202012"],"award-info":[{"award-number":["LSNFW202012"]}]},{"name":"Natural Science Fund Project, Department of Science and Technology of Liaoning Province","award":["2019-MS-282"],"award-info":[{"award-number":["2019-MS-282"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Accumulating evidence indicates that bisphenol A (BPA) analogs, including bisphenol B (BPB) and bisphenol S (BPS), disrupt testicular function and contribute to male reproductive dysfunction (MRD). However, whether BPA analogs are involved in MRD among middle-aged men remains inconclusive. Therefore, we selected cryptorchidism, erectile dysfunction, premature ejaculation, and testicular tumors as representative MRD conditions in middle-aged individuals, aiming to explore the molecular mechanisms that may be disrupted by bisphenols (BPs). By using GeneCards, STRING and Cytoscape, TP53, AKT1, and MYC were pinpointed as core targets associated with MRD. Enrichment analysis suggested that BPs may induce MRD by disrupting steroidogenesis. UPLC-MS\/MS analysis showed that both BPB and BPS exhibit specific accumulation in the testes. Following 20-day exposure to 0.3 or 0.6 mg\/kg body weight\/day BPB or BPS, testosterone levels and the expression of hub genes were decreased. The molecular docking results demonstrated that both BPB and BPS can directly bind to members of the cytochrome P450 family, potentially interfering with sex hormone biosynthesis. Our study identified the targets and mechanisms through which BPB and BPS induce MRD in middle-aged males, thereby providing insights for the safety assessment of BPs.<\/jats:p>","DOI":"10.3390\/ijms26199507","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:38:55Z","timestamp":1759246735000},"page":"9507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exposure to Bisphenol B and S Increases the Risk of Male Reproductive Dysfunction in Middle Age"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4892-992X","authenticated-orcid":false,"given":"Sen","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Bioscience and Biotechnology, Shenyang Agricultural University, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heliang","family":"Ni","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology, Shenyang Agricultural University, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xiao","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology, Shenyang Agricultural University, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Du","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection and Utilization of Aquatic Germplasm Resources, Ministry of Agriculture and Rural Affairs, Liaoning Ocean and Fisheries Science Research Institute, Dalian 116023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudong","family":"Han","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology, Shenyang Agricultural University, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenying","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology, Shenyang Agricultural University, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7078-7289","authenticated-orcid":false,"given":"Shuang","family":"Tang","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology, Shenyang Agricultural University, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2410-8004","authenticated-orcid":false,"given":"Mingxi","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Bioscience and Biotechnology, Shenyang Agricultural University, Shenyang 110866, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Adegoke, E.O., Rahman, M.S., and Pang, M.-G. 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