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However, there is currently no direct pharmacological evidence demonstrating that P\u2010gp and BCRP can reduce the occurrence of drug\u2010induced RTM. In this study, we chose small molecule targeted anti\u2010tumor agents as model drugs and systematically retrieved and collected information on the transporters and RTM for these drugs, followed by correlation analysis. The results showed a lower incidence of RTM for P\u2010gp substrate drugs, which aligns with previous knowledge. Surprisingly, BCRP substrate drugs exhibited higher rates of RTM in various dimensions, contradicting previous notions. This discrepancy may be attributed to the differential distribution and transport directions of P\u2010gp and BCRP on the blood\u2013testis barrier (BTB). For the first time, this study may provide clues that BCRP may facilitate the passage of exogenous compounds across the BTB, increasing the occurrence of RTM, rather than protecting spermatogenesis as traditionally believed. Furthermore, this study provides the first direct verification of the role of P\u2010gp in reducing RTM and protecting spermatogenesis.<\/jats:p>","DOI":"10.1111\/cts.70027","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T15:29:50Z","timestamp":1727882990000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Is there a possibility that P\u2010glycoprotein reduces reproductive toxicity in males but breast cancer resistance protein does not?"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4393-8886","authenticated-orcid":false,"given":"Zhiheng","family":"Yu","sequence":"first","affiliation":[{"name":"Pharmacy Department Peking University Third Hospital  Beijing China"},{"name":"Department of Obstetrics and Gynecology Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1773-5156","authenticated-orcid":false,"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Pharmacy Department Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Pharmacy Department Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Center for Reproductive Medicine, National Clinical Research Center for Obstetrics and Gynecology, Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology Peking University Third Hospital  Beijing China"},{"name":"Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Center for Reproductive Medicine, National Clinical Research Center for Obstetrics and Gynecology, Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology Peking University Third Hospital  Beijing China"},{"name":"State Key Laboratory of Female Fertility Promotion  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9678-2371","authenticated-orcid":false,"given":"Leslie Z.","family":"Benet","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, Schools of Pharmacy and Medicine University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-359X","authenticated-orcid":false,"given":"Suodi","family":"Zhai","sequence":"additional","affiliation":[{"name":"Pharmacy Department Peking University Third Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2010.11.007"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3028"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2004.05.010"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.003558"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118699"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118214"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90212-7"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/88.14.994"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.034751"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-009-1039-0"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604213"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2021.1893299"},{"key":"e_1_2_10_14_1","unstructured":"US FDA.Guidance for Industry Reproductive and Developmental Toxicities\u2014Integrating Study Results to Assess Concerns. 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