Two Hits of EDCs Three Generations Apart: Effects on Social Behaviors in Rats, and Analysis by Machine Learning.
Two Hits of EDCs Three Generations Apart: Effects on Social Behaviors in Rats, and Analysis by Machine Learning.
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DOI：
10.3390/toxics10010030
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发表时间：
2022-01-11
期刊：
影响因子：
4.6
通讯作者：
Gore AC
中科院分区：
文献类型：
--
作者：
Gillette R;Dias M;Reilly MP;Thompson LM;Castillo NJ;Vasquez EL;Crews D;Gore AC
所有人都直接暴露于现存的环境内分泌干扰化学品（EDCs），并通过我们祖先的跨代遗传间接暴露。虽然直接和祖先的接触都可能导致行为缺陷，但它们之间的相互作用尚不清楚。在这里，我们专注于社会行为的基础上，他们的直接或祖先暴露的脆弱性的证据，以及他们在繁殖和物种生存的重要性。利用一种新的“两次打击，三代相隔”的实验大鼠模型，我们研究了两类内分泌干扰物在六代之间的相互作用。将多氯联苯（一种弱雌激素混合物Aroclor 1221，1 mg/kg）、阿米洛唑林（抗雄激素，1 mg/kg）或溶剂（6% DMSO的芝麻油溶液）给予妊娠大鼠母鼠（F0），以直接暴露F1代，随后通过父系或母系进行繁殖。对F3母鼠进行第二次EDC打击，从而暴露F4代，并通过F6代进行育种。来自F1、F3、F4和F6代的约1200只雄性和雌性大鼠进行了社交性和社交新奇性测试，作为社交偏好的指标。我们利用DeepLabCut的机器学习来分析细微的社交行为，例如摸鼻子，其准确性与人类评分员相似。令人惊讶的是，社会行为受到影响的祖先暴露，但没有直接暴露的个人，特别是女性从父亲暴露的育种血统。EDC的影响各不相同：氟氯唑啉影响F3代的行为方面，而多氯联苯影响F3和F6代。综上所述，我们的数据表明，行为的特定方面特别容易受到EDC污染的遗传性祖先暴露的影响，存在性别差异，并且血统是跨代结果的关键因素。
All individuals are directly exposed to extant environmental endocrine-disrupting chemicals (EDCs), and indirectly exposed through transgenerational inheritance from our ancestors. Although direct and ancestral exposures can each lead to deficits in behaviors, their interactions are not known. Here we focused on social behaviors based on evidence of their vulnerability to direct or ancestral exposures, together with their importance in reproduction and survival of a species. Using a novel “two hits, three generations apart” experimental rat model, we investigated interactions of two classes of EDCs across six generations. PCBs (a weakly estrogenic mixture Aroclor 1221, 1 mg/kg), Vinclozolin (antiandrogenic, 1 mg/kg) or vehicle (6% DMSO in sesame oil) were administered to pregnant rat dams (F0) to directly expose the F1 generation, with subsequent breeding through paternal or maternal lines. A second EDC hit was given to F3 dams, thereby exposing the F4 generation, with breeding through the F6 generation. Approximately 1200 male and female rats from F1, F3, F4 and F6 generations were run through tests of sociability and social novelty as indices of social preference. We leveraged machine learning using DeepLabCut to analyze nuanced social behaviors such as nose touching with accuracy similar to a human scorer. Surprisingly, social behaviors were affected in ancestrally exposed but not directly exposed individuals, particularly females from a paternally exposed breeding lineage. Effects varied by EDC: Vinclozolin affected aspects of behavior in the F3 generation while PCBs affected both the F3 and F6 generations. Taken together, our data suggest that specific aspects of behavior are particularly vulnerable to heritable ancestral exposure of EDC contamination, that there are sex differences, and that lineage is a key factor in transgenerational outcomes.
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DOI：
10.1073/pnas.0610410104
发表时间：
2007-04-03
影响因子：
11.1
作者：
Crews, David;Gore, Andrea C.;Skinner, Michael K.
通讯作者：
Skinner, Michael K.
影响因子：
2.4
作者：
Haith, DA;Rossi, FS
通讯作者：
Rossi, FS
影响因子：
4.8
作者：
Kougias, Daniel G.;Cortes, Laura R.;Juraska, Janice M.
通讯作者：
Juraska, Janice M.
DOI：
10.1098/rspa.1937.0109
发表时间：
1937-05-01
影响因子：
--
作者：
Bartlett, MS
通讯作者：
Bartlett, MS
影响因子：
2.9
作者：
JOHNSTON, AL;FILE, SE
通讯作者：
FILE, SE