The potential regulatory role of non-coding RNAs in mifepristone-induced masculinization in Takifugu rubripes gonads

Abstract Background The regulatory roles of non-coding RNAs (ncRNAs) during sex differentiation in teleosts have received widespread attention recently. Mifepristone (RU486, a progesterone antagonist), which acts as an endocrine disruptor, can affect reproduction and sex differentiation in teleosts....

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Main Authors: Rui Gao, Hongwei Yan, Huiting Zhou, Mingtao Hu, Jia Wang, Xufang Shen, Meiyuan Li, Jinfeng Chen, Qi Liu, Ying Liu, Xiuli Wang, Qunwen Sun, He Zhou
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Genomics
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Online Access:https://doi.org/10.1186/s12864-025-11647-1
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author Rui Gao
Hongwei Yan
Huiting Zhou
Mingtao Hu
Jia Wang
Xufang Shen
Meiyuan Li
Jinfeng Chen
Qi Liu
Ying Liu
Xiuli Wang
Qunwen Sun
He Zhou
author_facet Rui Gao
Hongwei Yan
Huiting Zhou
Mingtao Hu
Jia Wang
Xufang Shen
Meiyuan Li
Jinfeng Chen
Qi Liu
Ying Liu
Xiuli Wang
Qunwen Sun
He Zhou
author_sort Rui Gao
collection DOAJ
description Abstract Background The regulatory roles of non-coding RNAs (ncRNAs) during sex differentiation in teleosts have received widespread attention recently. Mifepristone (RU486, a progesterone antagonist), which acts as an endocrine disruptor, can affect reproduction and sex differentiation in teleosts. Results The expression of ncRNAs in the gonads of tiger puffer (Takifugu rubripes) during RU486 (500 µg/g diet) induced masculinization process was examined by RNA-sequencing. A total of 4,381 long non-coding RNAs (lncRNAs), 309 circular RNAs (circRNAs), and 1,020 microRNAs (miRNAs) were identified. The expression of 41 differentially expressed (DE) lncRNAs and 20 DE miRNAs, which showed sexual dimorphic expression patterns in genetic female gonads in the control group (C-XX) vs. genetic male gonads in the control group (C-XY), were altered in genetic female gonads in the RU486 treated group (RU-XX). The genes targeted by DE ncRNAs were mainly enriched in sex-related pathways, such as calcium signaling, ovarian steroidogenesis, and cortisol synthesis and secretion. The results of co-expression and competing endogenous RNA (ceRNA) network analysis indicated that miRNAs (e.g., miR-205-z and fru-miR-122) and lncRNAs (including XR_003890915.1 and XR_003885862.1) may have pivotal roles, and lncRNAs (including XR_003890295.1, MSTRG.11750.1, and XR_003888827.1) may act as miRNA sponges, involved in the competition between miRNAs and sex-related genes during tiger puffer masculinization process. Dual luciferase reporter assay results identified that ovarian steroidogenesis related gene hsd17b1 is a downstream target of fru-miR-122. The expression of 4 lncRNAs, 4 circRNAs, and 6 miRNAs were validated by qPCR, indicating the accuracy and dependability of RNA-Seq. Conclusions This study provided the evidence that ncRNAs may participate in RU486-induced masculinization in T. rubripes, and may enhance our understanding of the regulatory network of sex differentiation in fugu.
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spelling doaj-art-53f1cd7bb6ec49309b6af99a8a3c20792025-08-20T02:32:07ZengBMCBMC Genomics1471-21642025-05-0126112010.1186/s12864-025-11647-1The potential regulatory role of non-coding RNAs in mifepristone-induced masculinization in Takifugu rubripes gonadsRui Gao0Hongwei Yan1Huiting Zhou2Mingtao Hu3Jia Wang4Xufang Shen5Meiyuan Li6Jinfeng Chen7Qi Liu8Ying Liu9Xiuli Wang10Qunwen Sun11He Zhou12Key Laboratory of Environment Controlled Aquaculture (Dalian Ocean University), Ministry of EducationKey Laboratory of Environment Controlled Aquaculture (Dalian Ocean University), Ministry of EducationKey Laboratory of Environment Controlled Aquaculture (Dalian Ocean University), Ministry of EducationKey Laboratory of Environment Controlled Aquaculture (Dalian Ocean University), Ministry of EducationKey Laboratory of Environment Controlled Aquaculture (Dalian Ocean University), Ministry of EducationKey Laboratory of Environment Controlled Aquaculture (Dalian Ocean University), Ministry of EducationKey Laboratory of Environment Controlled Aquaculture (Dalian Ocean University), Ministry of EducationKey Laboratory of Environment Controlled Aquaculture (Dalian Ocean University), Ministry of EducationKey Laboratory of Environment Controlled Aquaculture (Dalian Ocean University), Ministry of EducationKey Laboratory of Environment Controlled Aquaculture (Dalian Ocean University), Ministry of EducationCollege of Fisheries and Life Science, Dalian Ocean UniversityDalian Tian Zheng Co., LtdCollege of Fisheries and Life Science, Dalian Ocean UniversityAbstract Background The regulatory roles of non-coding RNAs (ncRNAs) during sex differentiation in teleosts have received widespread attention recently. Mifepristone (RU486, a progesterone antagonist), which acts as an endocrine disruptor, can affect reproduction and sex differentiation in teleosts. Results The expression of ncRNAs in the gonads of tiger puffer (Takifugu rubripes) during RU486 (500 µg/g diet) induced masculinization process was examined by RNA-sequencing. A total of 4,381 long non-coding RNAs (lncRNAs), 309 circular RNAs (circRNAs), and 1,020 microRNAs (miRNAs) were identified. The expression of 41 differentially expressed (DE) lncRNAs and 20 DE miRNAs, which showed sexual dimorphic expression patterns in genetic female gonads in the control group (C-XX) vs. genetic male gonads in the control group (C-XY), were altered in genetic female gonads in the RU486 treated group (RU-XX). The genes targeted by DE ncRNAs were mainly enriched in sex-related pathways, such as calcium signaling, ovarian steroidogenesis, and cortisol synthesis and secretion. The results of co-expression and competing endogenous RNA (ceRNA) network analysis indicated that miRNAs (e.g., miR-205-z and fru-miR-122) and lncRNAs (including XR_003890915.1 and XR_003885862.1) may have pivotal roles, and lncRNAs (including XR_003890295.1, MSTRG.11750.1, and XR_003888827.1) may act as miRNA sponges, involved in the competition between miRNAs and sex-related genes during tiger puffer masculinization process. Dual luciferase reporter assay results identified that ovarian steroidogenesis related gene hsd17b1 is a downstream target of fru-miR-122. The expression of 4 lncRNAs, 4 circRNAs, and 6 miRNAs were validated by qPCR, indicating the accuracy and dependability of RNA-Seq. Conclusions This study provided the evidence that ncRNAs may participate in RU486-induced masculinization in T. rubripes, and may enhance our understanding of the regulatory network of sex differentiation in fugu.https://doi.org/10.1186/s12864-025-11647-1RU486Takifugu rubripesncRNAsMasculinization
spellingShingle Rui Gao
Hongwei Yan
Huiting Zhou
Mingtao Hu
Jia Wang
Xufang Shen
Meiyuan Li
Jinfeng Chen
Qi Liu
Ying Liu
Xiuli Wang
Qunwen Sun
He Zhou
The potential regulatory role of non-coding RNAs in mifepristone-induced masculinization in Takifugu rubripes gonads
BMC Genomics
RU486
Takifugu rubripes
ncRNAs
Masculinization
title The potential regulatory role of non-coding RNAs in mifepristone-induced masculinization in Takifugu rubripes gonads
title_full The potential regulatory role of non-coding RNAs in mifepristone-induced masculinization in Takifugu rubripes gonads
title_fullStr The potential regulatory role of non-coding RNAs in mifepristone-induced masculinization in Takifugu rubripes gonads
title_full_unstemmed The potential regulatory role of non-coding RNAs in mifepristone-induced masculinization in Takifugu rubripes gonads
title_short The potential regulatory role of non-coding RNAs in mifepristone-induced masculinization in Takifugu rubripes gonads
title_sort potential regulatory role of non coding rnas in mifepristone induced masculinization in takifugu rubripes gonads
topic RU486
Takifugu rubripes
ncRNAs
Masculinization
url https://doi.org/10.1186/s12864-025-11647-1
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