Paternal phthalate exposure-elicited offspring metabolic disorders are associated with altered sperm small RNAs in mice.
Paternal phthalate exposure-elicited offspring metabolic disorders are associated with altered sperm small RNAs in mice.
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DOI：
10.1016/j.envint.2023.107769
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发表时间：
2023-02
影响因子：
11.8
通讯作者：
Zhou, Changcheng
中科院分区：
文献类型：
--
作者：
Liu, Jingwei;Shi, Junchao;Hernandez, Rebecca;Li, Xiuchun;Konchadi, Pranav;Miyake, Yuma;Chen, Qi;Zhou, Tong;Zhou, Changcheng
关键词：
暴露于无处不在的塑料相关内分泌干扰物（EDCs）与许多慢性疾病的风险增加有关。例如，邻苯二甲酸酯暴露与人类心脏代谢死亡率相关，社会成本约为390亿美元/年或更多。我们最近证明了几种广泛使用的塑料相关的内分泌干扰物在适当的小鼠模型中增加了心脏代谢疾病。除了影响成年人的健康，父母暴露于内分泌干扰物也被证明会导致后代的代谢紊乱，包括肥胖和糖尿病。虽然大多数研究都集中在母亲EDC暴露对后代健康的影响，但对父亲EDC暴露的影响知之甚少。在当前的研究中，我们调查了父亲暴露于普遍存在但研究不足的邻苯二甲酸二环己酯（DCHP）对小鼠F1和F2后代代谢健康的不良影响。父亲的DCHP暴露导致F1后代胰岛素抵抗加剧和胰岛素信号受损，而不影响饮食诱导的肥胖。我们先前表明，精子小的非编码RNA，包括tRNA衍生的小RNA（tsRNA）和rRNA衍生的小RNA（rsRNA）有助于父系获得性代谢紊乱的代际传递。使用一种新的PANDORA-seq，我们发现DCHP暴露会导致精子tsRNA/rsRNA景观变化，而传统的RNA-seq无法检测到这些变化，这可能有助于DCHP引起的不良反应。最后，我们发现，父亲的DCHP也可以导致性别特异性的跨代不利影响的F2后代和女性F2后代引起葡萄糖耐受不良。我们的研究结果表明，暴露于内分泌干扰邻苯二甲酸酯可能会对后代的代谢健康产生代际和跨代的不利影响。这些发现增加了我们对人类慢性疾病病因学的理解，这些疾病源于化学品引起的代际和跨代影响。
Exposure to ubiquitous plastic-associated endocrine disrupting chemicals (EDCs) is associated with the increased risk of many chronic diseases. For example, phthalate exposure is associated with cardiometabolic mortality in humans, with societal costs ~ $39 billion/year or more. We recently demonstrated that several widely used plastic-associated EDCs increase cardiometabolic disease in appropriate mouse models. In addition to affecting adult health, parental exposure to EDCs has also been shown to cause metabolic disorders, including obesity and diabetes, in the offspring. While most studies have focused on the impact of maternal EDC exposure on the offspring’s health, little is known about the effects of paternal EDC exposure. In the current study, we investigated the adverse impact of paternal exposure to a ubiquitous but understudied phthalate, dicyclohexyl phthalate (DCHP) on the metabolic health of F1 and F2 offspring in mice. Paternal DCHP exposure led to exacerbated insulin resistance and impaired insulin signaling in F1 offspring without affecting diet-induced obesity. We previously showed that sperm small non-coding RNAs including tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs) contribute to the intergenerational transmission of paternally acquired metabolic disorders. Using a novel PANDORA-seq, we revealed that DCHP exposure can lead to sperm tsRNA/rsRNA landscape changes that were undetected by traditional RNA-seq, which may contribute to DCHP-elicited adverse effects. Lastly, we found that paternal DCHP can also cause sex-specific transgenerational adverse effects in F2 offspring and elicited glucose intolerance in female F2 descendants. Our results suggest that exposure to endocrine disrupting phthalates may have intergenerational and transgenerational adverse effects on the metabolic health of their offspring. These findings increase our understanding of the etiology of chronic human diseases originating from chemical-elicited intergenerational and transgenerational effects.
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影响因子：
25
作者：
Gapp, Katharina;Jawaid, Ali;Sarkies, Peter;Bohacek, Johannes;Pelczar, Pawel;Prados, Julien;Farinelli, Laurent;Miska, Eric;Mansuy, Isabelle M.
通讯作者：
Mansuy, Isabelle M.
影响因子：
64.5
作者：
Carone BR;Fauquier L;Habib N;Shea JM;Hart CE;Li R;Bock C;Li C;Gu H;Zamore PD;Meissner A;Weng Z;Hofmann HA;Friedman N;Rando OJ
通讯作者：
Rando OJ
DOI：
10.1186/s12950-016-0147-y
发表时间：
2016
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
Ahmad R;Kochumon S;Thomas R;Atizado V;Sindhu S
通讯作者：
Sindhu S
基于柬埔寨总膳食研究的邻苯二甲酸酯膳食暴露和人类风险评估
影响因子：
8.3
作者：
Cheng, Zhang;Li, Han-Han;Wong, Ming-Hung
通讯作者：
Wong, Ming-Hung
DOI：
10.1080/19440049.2015.1079742
发表时间：
2015-11-02
影响因子：
2.9
作者：
Cao, Xu-Liang;Zhao, Wendy;Dabeka, Robert
通讯作者：
Dabeka, Robert