Differences in endocrine and reproductive responses to substance exposure across generations: highlighting the importance of complementary findings

IF 4.8 2区 医学 Q1 TOXICOLOGY Archives of Toxicology Pub Date : 2024-07-18 DOI:10.1007/s00204-024-03813-3
Ingo Bichlmaier
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Abstract

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.

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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。
本文分析了 112 项单代生殖毒性扩展研究的结果。目的是确定试验动物在同一代和不同代以及不同生命阶段是否表现出一致的内分泌和生殖效应。该分析以全面的二进制矩阵为基础,包括 530 种观察到的效应和 193 种独特的、具有统计学意义的关联。相关性的强度采用 Jaccard (J) 系数进行量化,以衡量同一研究中效应的共现情况。在整个数据集中,相关效应共现的频率很低(中位数 J = 0.231)。不过,也出现了一些特定的模式:与不同效应的关联(中位数 J = 0.222)相比,跨代相同效应的关联表现出更高的强度(中位数 J = 0.400)。值得注意的是,在成年第一代孝子(P1)和发育中的第二代孝子(dF2)的亲代动物中观察到的效应关联的 J 系数(中位数在 0.300 到 0.430 之间)比其他关联高出约两倍。与其他世代(中位数分别为 0.200 和 0.174)相比,P1 和 dF2 世代(中位数分别为 0.375 和 0.333)的等效生命阶段关联在统计学上显示出更高的关联强度。总之,在同一项研究中,相关效应同时出现的情况并不多见,而且与 P1 和 dF2 的效应相关性强于所有其他相关性。总体而言,由于相关效应的共同出现率普遍较低,这些发现强调了对每一代的每种效应进行独立分析的重要性,这对传统的毒性效应世代连续性预期提出了挑战。
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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
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.
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