文献类型：期刊文献

英文题名：Life-time levonorgestrel exposure causes intergenerational alterations of the thyroid-catecholaminergic-GABAergic functional network in zebrafish (Danio rerio)

作者：Hu, Xing[1];Cai, Qianlin[1];Wu, Junhao[2];Ye, Meixin[1];Yang, Jinlin[1];Huang, Hao[1];Liang, Weiyi[1];Zhang, Yutong[1];Shi, Ruolin[1];Liu, Yazi[1];Hou, Liping[1,3];Chen, Diyun[4]

机构：[1]Guangzhou Univ, Sch Life Sci, Guangzhou 510655, Peoples R China;[2]Guangdong Ocean Univ, Zhanjiang 524088, Peoples R China;[3]Guangzhou Univ, Sch Life Sci, Key Lab Conservat & Applicat Biodivers South China, Guangzhou 510006, Guangdong, Peoples R China;[4]Guangzhou Univ, Sch Environm Sci & Engn, Guangzhou 510655, Peoples R China

年份：2026

卷号：302

外文期刊名：ENVIRONMENTAL RESEARCH

收录：SCI-EXPANDED(收录号：WOS:001759450900001)、、EI(收录号：20261820609438)、WOS

基金：The authors greatly acknowledge the research fund provided by National Natural Science Foundation of China (22276043, 42230719, 42177262, 41977207) .

语种：英文

外文关键词：Levonorgestrel; Paternal exposure; Masculinization; Intergenerational toxicity; Thyroid disruption; Neurobehavioral toxicity

外文摘要：Levonorgestrel (LNG) is a prevalent contraceptive progestin frequently detected in aquatic systems. Although the endocrine disruptive effect of levonorgestrel on parental fish has been documented, its intergenerational effects at environmentally relevant concentrations remain unclear. In this study, zebrafish embryos were exposed to LNG at nominal concentrations of 0.0, 5.0, 50.0, or 500.0 ng L-1 from 2 h post fertilization (hpf) to 144 days post fertilization (dpf). Chronic exposure to LNG caused sex ratio skew toward males in zebrafish. These F0 males were subsequently crossed with solvent control females to establish the F1 lineages. Integrated transcriptomic and neurochemical analyzes revealed a thyro-catecholaminergic-GABAergic (TCGA) axis dysregulation, characterized by up-regulation of tpo, dio2, DBH and downregulation of gadA/B. This multi-level dysregulation converged on neurotransmitter imbalance: elevated dopamine (DA) and reduced gamma-aminobutyric acid (GABA), resulting in elevated triiodothyronine (T3) and reduced thyroxine (T4). These interdependent hormonal shifts were paternally transmitted to F1 offspring, manifesting as heritable hyperlocomotion. Elevated DNA methyltransferase (DNMT) activity and reduced Ten-eleven translocation (TET) activity in the F0 testes and 120 hpf F1 larvae suggested altered DNA methylation maintenance capacity. In addition, paternal exposure led to reduced fecundity, survival, and motor deficits in F1 offspring. Our data indicate that LNG at concentrations from 5 ng L-1 upward disrupts the integrated TCGA axis, with DNMT/TET alterations suggesting potential paternal epigenetic mechanisms, supporting a framework for progestin-induced intergenerational toxicity.