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Scientific Reports · 2017 ·Vol. 7 ·期 1 ·1-8 · IF 4.259

Effect of environmentally-relevant concentrations of nonylphenol on sexual differentiation in zebrafish: a multi-generational study

Sun Dong,Chen Qi,He Ning,Diao Pan-pan,Jia Li-xing,Duan Shun-shan

Nonylphenol (NP) is a persistent environmental chemical that can disrupt the organism’s endocrine system, and is detected in the surface water and sea. In this study, we investigated whether NP can alter transcriptional expression of sexual differentiation-related genes. Three generations of zebrafish were exposed to 0, 2, 20 and 200 μg·L −1 of NP, and transcriptional expression of sexual differentiation genes were assessed in 10, 20 and 40 dpf in the F1 and F2 generations. Growth of zebrafish exposed to 200 μg·L −1 of NP was inhibited at 125 dpf in the F1 generation. 20 μg·L −1 of NP resulted in 80% females in the F1 generation, but had no effect on the F2 generation. In terms of the sexual differentiation genes, the transcriptional expression of cyp19a1a and esr1 genes were upregulated in 20 μg·L −1 of NP in the F1 generation. But expression of the sexual differentiation genes were not affected in the F2 generation. Overall, NP could affect sexual differentiation and gene transcriptional expression in the F1 generation. The tolerance of contaminant in the offsprings was improved at low concentration.

研究领域: 环境科学 · 毒理学 · 内分泌学 · 水生生物学
✓ 已验证 DOI PubMed 高影响因子
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PLoS Genetics · 2024 ·Vol. 20 ·期 3 ·e1011170 · IF 4

New insights into the all-testis differentiation in zebrafish with compromised endogenous androgen and estrogen synthesis

Yonglin Ruan,Xuehui Li,Xinyi Wang,Gang Zhai,Qiyong Lou,Xia Jin,Jiangyan He,Jie Mei,Wuhan Xiao,Jianfang Gui,Zhan Yin

The regulatory mechanism of gonadal sex differentiation, which is complex and regulated by multiple factors, remains poorly understood in teleosts. Recently, we have shown that compromised androgen and estrogen synthesis with increased progestin leads to all-male differentiation with proper testis development and spermatogenesis in cytochrome P450 17a1 ( cyp17a1 )-/- zebrafish. In the present study, the phenotypes of female-biased sex ratio were positively correlated with higher Fanconi anemia complementation group L ( fancl ) expression in the gonads of doublesex and mab-3 related transcription factor 1 ( dmrt1 )-/- and cyp17a1 -/-; dmrt1 -/- fish. The additional depletion of fancl in cyp17a1 -/-; dmrt1 -/- zebrafish reversed the gonadal sex differentiation from all-ovary to all-testis (in cyp17a1 -/-; dmrt1 -/-; fancl -/- fish). Luciferase assay revealed a synergistic inhibitory effect of Dmrt1 and androgen signaling on fancl transcription. Furthermore, an interaction between Fancl and the apoptotic factor Tumour protein p53 (Tp53) was found in vitro . The interaction between Fancl and Tp53 was observed via the WD repeat domain (WDR) and C-terminal domain (CTD) of Fancl and the DNA binding domain (DBD) of Tp53, leading to the K48-linked polyubiquitination degradation of Tp53 activated by the ubiquitin ligase, Fancl. Our results show that testis fate in cyp17a1 -/- fish is determined by Dmrt1, which is thought to stabilize Tp53 by inhibiting fancl transcription during the critical stage of sexual fate determination in zebrafish. Gonadal sex differentiation is known as the queen of problems in evolutionary biology, and the mechanisms that determine sexual fate vary widely among teleosts. Traditionally, Dmrt1 and androgen signaling have been essential for testis differentiation, and estrogen signaling has been essential for ovary differentiation. The all-testis phenotype observed in cyp17a1 -/- zebrafish, has led to the conclusion that androgen signaling is dispensable for testis differentiation in zebrafish. By analyzing a series of mutant zebrafish lines, we show here that Dmrt1 sufficiently promotes all-testis differentiation in cyp17a1 -deficient zebrafish albeit the compromised androgen and estrogen synthesis. In addition, we observed that zebrafish Dmrt1 and androgen signaling probably stabilize Tp53 by inhibiting the transcription of a ubiquitin ligase, Fancl. Our current study provides new insights into the interactive signals that regulate sexual fate determination in teleosts.

CAS / MDL: 67-68-5
研究领域: 发育生物学 · 分子生物学 · 遗传学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Genes · 2024 ·Vol. 15 ·期 5 ·605 · IF 2.8

Molecular and Physiological Effects of 17α-methyltestosterone on Sex Differentiation of Black Rockfish, Sebastes schlegelii

Haijun Huang,Yuyan Liu,Qian Wang,Caichao Dong,Le Dong,Jingjing Zhang,Yu Yang,Xiancai Hao,Weijing Li,Ivana F. Rosa,Lucas B. Doretto,Xuebin Cao,Changwei Shao

It is widely known that all-female fish production holds economic value for aquaculture.Sebastes schlegelii, a preeminent economic species, exhibits a sex dimorphism, with females surpassing males in growth. In this regard, achieving all-female black rockfish production could significantly enhance breeding profitability. In this study, we utilized the widely used male sex-regulating hormone, 17α-methyltestosterone (MT) at three different concentrations (20, 40, and 60 ppm), to produce pseudomales ofS. schlegeliifor subsequent all-female offspring breeding. Long-term MT administration severely inhibits the growth ofS. schlegelii, while short term had no significant impact. Histological analysis confirmed sex reversal at all MT concentrations; however, both medium and higher MT concentrations impaired testis development. MT also influenced sex steroid hormone levels in pseudomales, suppressing E2 while increasing T and 11-KT levels. In addition, a transcriptome analysis revealed that MT down-regulated ovarian-related genes (cyp19a1aandfoxl2) while up-regulating male-related genes (amh) in pseudomales. Furthermore, MT modulated the TGF-β signaling and steroid hormone biosynthesis pathways, indicating its crucial role inS. schlegeliisex differentiation. Therefore, the current study provides a method for achieving sexual reversal using MT inS. schlegeliiand offers an initial insight into the underlying mechanism of sexual reversal in this species.

研究领域: 水产养殖 · 内分泌学 · 分子生物学 · 生理学
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