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Zebrafish cyp17a1 knockout reveals that androgen-mediated signaling is important for male brain sex differentiation
Shu, Tingting1,2; Zhai, Gang1; Pradhan, Ajay3; Olsson, Per-Erik3; Yin, Zhan1
Corresponding AuthorPradhan, Ajay(Ajay.Pradhan@oru.se) ; Yin, Zhan(zyin@ihb.ac.cn)
2020-09-01
Source PublicationGENERAL AND COMPARATIVE ENDOCRINOLOGY
ISSN0016-6480
Volume295Pages:9
AbstractBrain 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.
KeywordBrain dimorphism Neurons RNA sequencing Sexual dimorphism Steroids
DOI10.1016/j.ygcen.2020.113490
Funding OrganizationNational 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
Indexed BySCI ; SCI
Language英语
Funding ProjectNational 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 Research AreaEndocrinology & Metabolism
WOS SubjectEndocrinology & Metabolism
WOS IDWOS:000555112400002
WOS KeywordDIMORPHIC GENE-EXPRESSION ; DANIO-RERIO ; BEHAVIOR ; MASCULINIZATION ; DISRUPTION ; MECHANISMS ; OBESITY ; LEADS ; MICE
PublisherACADEMIC PRESS INC ELSEVIER SCIENCE
Funding OrganizationNational 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
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/36796
Collection中科院水生所知识产出(2009年前)
Corresponding AuthorPradhan, Ajay; Yin, Zhan
Affiliation1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
2.Univ Chinese Acad Sci, Beijing 101408, Peoples R China
3.Orebro Univ, Life Sci Ctr, Sch Sci & Technol, SE-70182 Orebro, Sweden
Recommended Citation
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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