Knowledge Management System Of Guangzhou Institute of Geochemistry，CAS
| Long, Xiao-Bing1,2,3; Shi, Wen-Jun1,2,3; Yao, Chong-Rui1,2,3; Li, Si-Ying1,2,3; Zhang, Jin-Ge1,2,3; Lu, Zhi-Jie1,2,3; Ma, Dong-Dong1,2,3; Jiang, Yu-Xia4,5; Ying, Guang-Guo1,2,3 | |
| Norethindrone suppress the germ cell development via androgen receptor resulting in male bias | |
| Source Publication | AQUATIC TOXICOLOGY
 |
| ISSN | 0166-445X |
| 2023-08-01 | |
| Volume | 261Pages:9 |
| DOI | 10.1016/j.aquatox.2023.106604 |
| Language | 英语 |
| WOS Research Area | Marine & Freshwater Biology ; Toxicology |
| Abstract | Progestins are widely used and detected in surface waters, and can affect gonad development and sexual dif-ferentiation in fish. However, the toxicological mechanisms of sexual differentiation induced by progestins are not well understood. Here, we investigated the effects of norethindrone (NET) and androgen receptor (AR) antagonist flutamide (FLU) on gonadal differentiation in zebrafish from 21 dpf (days post-fertilization) to 49 dpf. The results showed that NET caused male bias, while FLU resulted in female bias at 49 dpf. The NET and FLU mixtures significantly decreased the percentage of males compared to the NET single exposure. Molecular docking analysis showed that FLU and NET had similar docking pocket and docking posture with AR resulting in competitively forming the hydrogen bond with Thr334 of AR. These results suggested that binding to AR was the molecular initiating event of sex differentiation induced by NET. Moreover, NET strongly decreased transcription of biomarker genes (dnd1, ddx4, dazl, piwil1 and nanos1) involved in germ cell development, while FLU signif-icantly increased transcription of these target genes. There was an increase in the number of juvenile oocytes, which was consistent with the female bias in the combined groups. The bliss independence model analysis further showed that NET and FLU had antagonistic effect on transcription and histology during gonadal dif-ferentiation. Thus, NET suppressed the germ cell development via AR, resulting in male bias. Understanding the molecular initiation of sex differentiation in progestins is essential to provide a comprehensive biological basis for ecological risk assessment. |
| Keyword | Norethindrone Germ cells Androgen receptor Molecular docking Male bias |
| WOS ID | WOS:001023790300001 |
| Indexed By | SCI |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.gig.ac.cn/handle/344008/74415 |
| Collection | 有机地球化学国家重点实验室 |
| Corresponding Author | Shi, Wen-Jun |
| Affiliation | 1.South China Normal Univ, SCNU Environm Res Inst, Guangdong Prov Key Lab Chem Pollut & Environm Safe, Guangzhou 510006, Peoples R China 2.South China Normal Univ, MOE Key Lab Theoret Chem Environm, Guangzhou 510006, Peoples R China 3.South China Normal Univ, Sch Environm, Guangzhou 510006, Peoples R China 4.Chinese Acad Sci, Guangzhou Inst Geochem, State Key Lab Organ Geochem, Guangzhou 510640, Peoples R China 5.Minist Ecol & Environm, South China Inst Environm Sci, Guangzhou 510535, Peoples R China |
| Recommended Citation GB/T 7714 | Long, Xiao-Bing,Shi, Wen-Jun,Yao, Chong-Rui,et al. Norethindrone suppress the germ cell development via androgen receptor resulting in male bias[J]. AQUATIC TOXICOLOGY,2023,261:9. |
| APA | Long, Xiao-Bing.,Shi, Wen-Jun.,Yao, Chong-Rui.,Li, Si-Ying.,Zhang, Jin-Ge.,...&Ying, Guang-Guo.(2023).Norethindrone suppress the germ cell development via androgen receptor resulting in male bias.AQUATIC TOXICOLOGY,261,9. |
| MLA | Long, Xiao-Bing,et al."Norethindrone suppress the germ cell development via androgen receptor resulting in male bias".AQUATIC TOXICOLOGY 261(2023):9. |
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