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Zebrafish cyp17a1 knockout reveals that androgen-mediated signaling is important for male brain sex differentiation

文献类型：期刊论文

作者Shu, Tingting2,3; Zhai, Gang2; Pradhan, Ajay1; Olsson, Per-Erik1; Yin, Zhan2
刊名GENERAL AND COMPARATIVE ENDOCRINOLOGY
出版日期2020-09-01
卷号295页码:9
ISSN号0016-6480
关键词Brain dimorphism Neurons RNA sequencing Sexual dimorphism Steroids
DOI10.1016/j.ygcen.2020.113490
通讯作者Pradhan, Ajay(Ajay.Pradhan@oru.se) ; Yin, Zhan(zyin@ihb.ac.cn)
英文摘要Brain sex differentiation is a complex process, wherein genes and steroid hormones act to induce specific gender brain differentiation. Testosterone (T) derived from the gonads has been linked to neural circuit modeling in a sex-specific manner. Previously, we have shown that cyp17a1 knockout (KO) zebrafish have low plasma androgen levels, and display compromised male-typical mating behaviors. In this study, we demonstrated that treatment of cyp17a1 KO males with T or 11-ketotestosterone (11-KT) is sufficient to rescue mating impairment by restoring the male-typical secondary sex characters (SSCs) and mating behaviors, confirming an essential role of androgen in maintaining SSCs and mating behaviors. Brain steroid hormone analysis revealed that cyp17a1 KO fish have reduced levels of T and 11-KT. We performed RNA sequencing on brain samples of control and cyp17a1 KO male zebrafish to get insights regarding the impact of cyp17a1 KO on gene expression pattern, and to correlate it with the observed disruption of male-typical mating behaviors. Transcriptome analysis of cyp17a1 KO males showed a differential gene expression when compared to control males. In total, 358 genes were differentially regulated between control males and KO males. Important genes including brain aromatase (cyp19a1b), progesterone receptor (pgr), deiodinase (dio2), and insulin-like growth factor 1 (igf1) that are involved in brain functions, as well as androgen response genes including igf1, frem1a, elovl1a, pax3a, mmp13b, hsc70, ogg1 were regulated. RT-qPCR analysis following rescue of cyp17a1 KO with T and 11-KT further suggested that androgen-mediated signaling is disrupted in the cyp17a1 KO fish. Our results indicated that cyp17a1 KO fish have an incomplete masculinization and altered brain gene expression, which could be due to decreased androgen levels.
WOS关键词DIMORPHIC GENE-EXPRESSION ; DANIO-RERIO ; BEHAVIOR ; MASCULINIZATION ; DISRUPTION ; MECHANISMS ; OBESITY ; LEADS ; MICE
资助项目National Key Research and Development Program, China[2018YFD0900205] ; National Natural Science Foundation, China[31530077] ; Swedish Research Council[2015-04600] ; Knowledge foundation, Sweden[20170231] ; Edla Johansson's Scientific Foundation ; Orebro University
WOS研究方向Endocrinology & Metabolism
语种英语
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号WOS:000555112400002
资助机构National Key Research and Development Program, China ; National Key Research and Development Program, China ; National Key Research and Development Program, China ; National Key Research and Development Program, China ; National Natural Science Foundation, China ; National Natural Science Foundation, China ; National Natural Science Foundation, China ; National Natural Science Foundation, China ; Swedish Research Council ; Swedish Research Council ; Swedish Research Council ; Swedish Research Council ; Knowledge foundation, Sweden ; Knowledge foundation, Sweden ; Knowledge foundation, Sweden ; Knowledge foundation, Sweden ; Edla Johansson's Scientific Foundation ; Edla Johansson's Scientific Foundation ; Edla Johansson's Scientific Foundation ; Edla Johansson's Scientific Foundation ; Orebro University ; Orebro University ; Orebro University ; Orebro University ; National Key Research and Development Program, China ; National Key Research and Development Program, China ; National Key Research and Development Program, China ; National Key Research and Development Program, China ; National Natural Science Foundation, China ; National Natural Science Foundation, China ; National Natural Science Foundation, China ; National Natural Science Foundation, China ; Swedish Research Council ; Swedish Research Council ; Swedish Research Council ; Swedish Research Council ; Knowledge foundation, Sweden ; Knowledge foundation, Sweden ; Knowledge foundation, Sweden ; Knowledge foundation, Sweden ; Edla Johansson's Scientific Foundation ; Edla Johansson's Scientific Foundation ; Edla Johansson's Scientific Foundation ; Edla Johansson's Scientific Foundation ; Orebro University ; Orebro University ; Orebro University ; Orebro University ; National Key Research and Development Program, China ; National Key Research and Development Program, China ; National Key Research and Development Program, China ; National Key Research and Development Program, China ; National Natural Science Foundation, China ; National Natural Science Foundation, China ; National Natural Science Foundation, China ; National Natural Science Foundation, China ; Swedish Research Council ; Swedish Research Council ; Swedish Research Council ; Swedish Research Council ; Knowledge foundation, Sweden ; Knowledge foundation, Sweden ; Knowledge foundation, Sweden ; Knowledge foundation, Sweden ; Edla Johansson's Scientific Foundation ; Edla Johansson's Scientific Foundation ; Edla Johansson's Scientific Foundation ; Edla Johansson's Scientific Foundation ; Orebro University ; Orebro University ; Orebro University ; Orebro University ; National Key Research and Development Program, China ; National Key Research and Development Program, China ; National Key Research and Development Program, China ; National Key Research and Development Program, China ; National Natural Science Foundation, China ; National Natural Science Foundation, China ; National Natural Science Foundation, China ; National Natural Science Foundation, China ; Swedish Research Council ; Swedish Research Council ; Swedish Research Council ; Swedish Research Council ; Knowledge foundation, Sweden ; Knowledge foundation, Sweden ; Knowledge foundation, Sweden ; Knowledge foundation, Sweden ; Edla Johansson's Scientific Foundation ; Edla Johansson's Scientific Foundation ; Edla Johansson's Scientific Foundation ; Edla Johansson's Scientific Foundation ; Orebro University ; Orebro University ; Orebro University ; Orebro University
源URL[http://ir.ihb.ac.cn/handle/342005/36795]  
专题水生生物研究所_中科院水生所知识产出（2009年前）
通讯作者Pradhan, Ajay; Yin, Zhan
作者单位1.Orebro Univ, Life Sci Ctr, Sch Sci & Technol, SE-70182 Orebro, Sweden
2.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
3.Univ Chinese Acad Sci, Beijing 101408, Peoples R China
推荐引用方式
GB/T 7714		 Shu, Tingting,Zhai, Gang,Pradhan, Ajay,et al. Zebrafish cyp17a1 knockout reveals that androgen-mediated signaling is important for male brain sex differentiation[J]. GENERAL AND COMPARATIVE ENDOCRINOLOGY,2020,295:9.
APA Shu, Tingting,Zhai, Gang,Pradhan, Ajay,Olsson, Per-Erik,&Yin, Zhan.(2020).Zebrafish cyp17a1 knockout reveals that androgen-mediated signaling is important for male brain sex differentiation.GENERAL AND COMPARATIVE ENDOCRINOLOGY,295,9.
MLA Shu, Tingting,et al."Zebrafish cyp17a1 knockout reveals that androgen-mediated signaling is important for male brain sex differentiation".GENERAL AND COMPARATIVE ENDOCRINOLOGY 295(2020):9.

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来源：水生生物研究所

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