{"title":"各代人的内分泌和生殖系统对药物接触反应的差异:强调补充性研究结果的重要性。","authors":"Ingo Bichlmaier","doi":"10.1007/s00204-024-03813-3","DOIUrl":null,"url":null,"abstract":"<div><p>This article analyzes the results from 112 Extended One-Generation Reproductive Toxicity studies. The objective was to determine if test animals show consistent endocrine and reproductive effects within the same and across different generations and life stages. The analysis, grounded in a comprehensive Binary Matrix, included 530 observed effects and 193 unique, statistically significant associations. Associations’ strength was quantified using Jaccard (<b><i>J</i></b>) coefficients to measure effect co-occurrence in the same study. Associated effects co-occur infrequently across the whole dataset (median <b><i>J</i></b> = 0.231). However, specific patterns emerged: associations of same effects across generations exhibited a higher strength (median <b><i>J</i></b> = 0.400) compared to associations of different effects (median <b><i>J</i></b> = 0.222). Notably, associations with effects observed in both the parental animals of the adult first filial generation (P1) and developing second filial generations (dF2) demonstrated <b><i>J</i></b> coefficients (with medians ranging from 0.300 to 0.430) that were approximately twofold higher than those of other associations. Consistently, equivalent life stage associations across generations revealed statistically significant higher association strengths for the P1 and dF2 generations (median<i>s</i> of 0.375 and 0.333, respectively) compared to other generations (medians of 0.200 and 0.174), possibly due to longer exposure duration and altered cross-talk between pregnant P1 dam and its conceptus. Overall, it is concluded that co-occurrence of associated effects in the same study is rather infrequent and that associations with effects in P1 and dF2 are stronger than all other associations. In general, the findings underscore the importance of independently analyzing each effect per generation due to the generally low co-occurrence rates of associated effects, challenging traditional expectations of generational continuity in toxic effects.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"98 10","pages":"3215 - 3230"},"PeriodicalIF":4.8000,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402854/pdf/","citationCount":"0","resultStr":"{\"title\":\"Differences in endocrine and reproductive responses to substance exposure across generations: highlighting the importance of complementary findings\",\"authors\":\"Ingo Bichlmaier\",\"doi\":\"10.1007/s00204-024-03813-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>This article analyzes the results from 112 Extended One-Generation Reproductive Toxicity studies. The objective was to determine if test animals show consistent endocrine and reproductive effects within the same and across different generations and life stages. The analysis, grounded in a comprehensive Binary Matrix, included 530 observed effects and 193 unique, statistically significant associations. Associations’ strength was quantified using Jaccard (<b><i>J</i></b>) coefficients to measure effect co-occurrence in the same study. Associated effects co-occur infrequently across the whole dataset (median <b><i>J</i></b> = 0.231). However, specific patterns emerged: associations of same effects across generations exhibited a higher strength (median <b><i>J</i></b> = 0.400) compared to associations of different effects (median <b><i>J</i></b> = 0.222). Notably, associations with effects observed in both the parental animals of the adult first filial generation (P1) and developing second filial generations (dF2) demonstrated <b><i>J</i></b> coefficients (with medians ranging from 0.300 to 0.430) that were approximately twofold higher than those of other associations. Consistently, equivalent life stage associations across generations revealed statistically significant higher association strengths for the P1 and dF2 generations (median<i>s</i> of 0.375 and 0.333, respectively) compared to other generations (medians of 0.200 and 0.174), possibly due to longer exposure duration and altered cross-talk between pregnant P1 dam and its conceptus. Overall, it is concluded that co-occurrence of associated effects in the same study is rather infrequent and that associations with effects in P1 and dF2 are stronger than all other associations. In general, the findings underscore the importance of independently analyzing each effect per generation due to the generally low co-occurrence rates of associated effects, challenging traditional expectations of generational continuity in toxic effects.</p></div>\",\"PeriodicalId\":8329,\"journal\":{\"name\":\"Archives of Toxicology\",\"volume\":\"98 10\",\"pages\":\"3215 - 3230\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-07-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11402854/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s00204-024-03813-3\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Toxicology","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s00204-024-03813-3","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
Differences in endocrine and reproductive responses to substance exposure across generations: highlighting the importance of complementary findings
This article analyzes the results from 112 Extended One-Generation Reproductive Toxicity studies. The objective was to determine if test animals show consistent endocrine and reproductive effects within the same and across different generations and life stages. The analysis, grounded in a comprehensive Binary Matrix, included 530 observed effects and 193 unique, statistically significant associations. Associations’ strength was quantified using Jaccard (J) coefficients to measure effect co-occurrence in the same study. Associated effects co-occur infrequently across the whole dataset (median J = 0.231). However, specific patterns emerged: associations of same effects across generations exhibited a higher strength (median J = 0.400) compared to associations of different effects (median J = 0.222). Notably, associations with effects observed in both the parental animals of the adult first filial generation (P1) and developing second filial generations (dF2) demonstrated J coefficients (with medians ranging from 0.300 to 0.430) that were approximately twofold higher than those of other associations. Consistently, equivalent life stage associations across generations revealed statistically significant higher association strengths for the P1 and dF2 generations (medians of 0.375 and 0.333, respectively) compared to other generations (medians of 0.200 and 0.174), possibly due to longer exposure duration and altered cross-talk between pregnant P1 dam and its conceptus. Overall, it is concluded that co-occurrence of associated effects in the same study is rather infrequent and that associations with effects in P1 and dF2 are stronger than all other associations. In general, the findings underscore the importance of independently analyzing each effect per generation due to the generally low co-occurrence rates of associated effects, challenging traditional expectations of generational continuity in toxic effects.
期刊介绍:
Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.