PMID- 23349717 OWN - NLM STAT- MEDLINE DCOM- 20130709 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 1 DP - 2013 TI - Transcriptomic analyses of sexual dimorphism of the zebrafish liver and the effect of sex hormones. PG - e53562 LID - 10.1371/journal.pone.0053562 [doi] LID - e53562 AB - The liver is one of the most sex-dimorphic organs in both oviparous and viviparous animals. In order to understand the molecular basis of the difference between male and female livers, high-throughput RNA-SAGE (serial analysis of gene expression) sequencing was performed for zebrafish livers of both sexes and their transcriptomes were compared. Both sexes had abundantly expressed genes involved in translation, coagulation and lipid metabolism, consistent with the general function of the liver. For sex-biased transcripts, from in addition to the high enrichment of vitellogenin transcripts in spawning female livers, which constituted nearly 80% of total mRNA, it is apparent that the female-biased genes were mostly involved in ribosome/translation, estrogen pathway, lipid transport, etc, while the male-biased genes were enriched for oxidation reduction, carbohydrate metabolism, coagulation, protein transport and localization, etc. Sexual dimorphism on xenobiotic metabolism and anti-oxidation was also noted and it is likely that retinol x receptor (RXR) and liver x receptor (LXR) play central roles in regulating the sexual differences of lipid and cholesterol metabolisms. Consistent with high ribosomal/translational activities in the female liver, female-biased genes were significantly regulated by two important transcription factors, Myc and Mycn. In contrast, Male livers showed activation of transcription factors Ppargc1b, Hnf4a, and Stat4, which regulate lipid and glucose metabolisms and various cellular activities. The transcriptomic responses to sex hormones, 17beta-estradiol (E2) or 11-keto testosterone (KT11), were also investigated in both male and female livers and we found that female livers were relatively insensitive to sex hormone disturbance, while the male livers were readily affected. E2 feminized male liver by up-regulating female-biased transcripts and down-regulating male-biased transcripts. The information obtained in this study provides comprehensive insights into the sexual dimorphism of zebrafish liver transcriptome and will facilitate further development of the zebrafish as a human liver disease model. FAU - Zheng, Weiling AU - Zheng W AD - Department of Biological Sciences, National University of Singapore, Singapore, Singapore. FAU - Xu, Hongyan AU - Xu H FAU - Lam, Siew Hong AU - Lam SH FAU - Luo, Huaien AU - Luo H FAU - Karuturi, R Krishna Murthy AU - Karuturi RK FAU - Gong, Zhiyuan AU - Gong Z LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130117 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Gonadal Steroid Hormones) RN - 0 (RNA, Messenger) RN - 0 (Xenobiotics) SB - IM MH - Animals MH - Female MH - *Gene Expression Profiling MH - Gene Regulatory Networks/drug effects MH - Gonadal Steroid Hormones/*pharmacology MH - Humans MH - Liver/*drug effects/*metabolism MH - Male MH - RNA, Messenger/genetics/metabolism MH - Sequence Analysis, RNA MH - *Sex Characteristics MH - Xenobiotics/metabolism MH - Zebrafish/*genetics/metabolism PMC - PMC3547925 COIS- Competing Interests: Co-author Zhiyuan Gongis is a PLOS ONE Editorial Board member. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. EDAT- 2013/01/26 06:00 MHDA- 2013/07/10 06:00 PMCR- 2013/01/17 CRDT- 2013/01/26 06:00 PHST- 2012/09/09 00:00 [received] PHST- 2012/11/29 00:00 [accepted] PHST- 2013/01/26 06:00 [entrez] PHST- 2013/01/26 06:00 [pubmed] PHST- 2013/07/10 06:00 [medline] PHST- 2013/01/17 00:00 [pmc-release] AID - PONE-D-12-27355 [pii] AID - 10.1371/journal.pone.0053562 [doi] PST - ppublish SO - PLoS One. 2013;8(1):e53562. doi: 10.1371/journal.pone.0053562. Epub 2013 Jan 17.