Simultaneous exposure to estrogen and androgen resulted in feminization and endocrine disruption

Chen, Lili; Jiang, Xiaolong; Feng, Haiwei; Shi, Hongjuan; Sun, Lina; Xi, Qingping; Wang, Deshou

doi:10.1530/joe-15-0432

Cited by 31 publications

(8 citation statements)

References 65 publications

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“…Estrogen, synthesized by Cyp19a1, plays a critical role in teleost ovarian differentiation and maintenance (D'Cotta et al, ; Wang et al, ; Guiguen et al, ). In the present study, F2 XY gsdf −/− fish displayed male‐to‐female sex reversal with functional ovaries, which phenocopies sex reversal effects of exogenous application of estradiol‐17β to XY Nile tilapia (Chen et al, ). In both cases, early expression of Dmrt1 gradually disappeared in the gonad, probably due to the up‐regulation of Cyp19a1a, which increased estrogen production at the early stages of sex differentiation.…”

Section: Discussionsupporting

confidence: 67%

gsdf is a downstream gene of dmrt1 that functions in the male sex determination pathway of the Nile tilapia

Jiang

Yang

et al. 2016

Molecular Reproduction Devel

126

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Gonadal soma-derived factor (gsdf) is critical for testicular differentiation in teleosts, yet detailed analysis of Gsdf on testicular differentiation is lacking. In the present study, we knocked out tilapia gsdf using CRISPR/Cas9. F0 gsdf-deficient XY fish with high mutation rate (≥58%) developed as intersex, with ovotestes 90 days after hatching (dah), and become completely sex-reversed with ovaries at 180 and 240 dah. Those individuals with a low mutation rate (<58%) and XY gsdf(+/-) fish developed as males with normal testes. In F2 XY gsdf(-/-) fish, the gonads first expressed Dmrt1, which initiated the male pathway at 10 dah, then both male and female pathways were activated, as reflected by the simultaneous expression of Dmrt1 and Cyp19a1a in different cell populations at 18 dah, shifted to the female pathway expressing only Cyp19a1a at 36 dah, and finally developed into functional ovaries as adults. The male pathway and Dmrt1 expression was initiated, but failed to be maintained, in the absence of Gsdf. Aromatase-inhibitor treatment from 10 to 35 dah, however, rescued the phenotype, resulting in XY gsdf(-/-) with normal testes that expressed Dmrt1 and Cyp11b2. In vitro promoter analyses demonstrated that Dmrt1 activated gsdf expression in a dose-dependent manner in the presence of Sf1, even though Dmrt1 alone could not. Taken together, our results demonstrated that gsdf is a downstream gene of dmrt1. Gsdf probably inhibits estrogen production to trigger testicular differentiation. Mol. Reprod. Dev. 83: 497-508, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 67%

gsdf is a downstream gene of dmrt1 that functions in the male sex determination pathway of the Nile tilapia

Jiang

Yang

et al. 2016

Molecular Reproduction Devel

126

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“…In an aging society it is very likely that more and more pharmaceuticals will be released in the environment. Human hormones as 17β-estradiol or the contraceptive 17α-ethinyl estradiol have been reported to lead to feminization or sexual disruption of fish (Chen et al 2016a; Orn et al 2016). Other estrogens as estrone which is predominant in menopausal women and estriol, a metabolite of estrone and 17β-estradiol, are also found in wastewaters (Auriol et al 2007a, b).…”

Section: Introductionmentioning

confidence: 99%

Expression of a new laccase from Moniliophthora roreri at high levels in Pichia pastoris and its potential application in micropollutant degradation

et al. 2017

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Laccases have gained significant attention due to their emerging applications including bioremediation, biomass degradation and biofuel cells. One of the prerequisites for the industrial application of laccases is their sufficient availability. However, expression levels of recombinantly expressed laccases are often low. In this study Mrl2, a new laccase from the basidiomycete Moniliophthora roreri, was cloned in Pichia pastoris and produced in an optimized fed-batch process at an exceptionally high yield of 1.05 g l−1. With a redox potential of 0.58 V, Mrl2 belongs to mid-redox potential laccases. However, Mrl2 demonstrated high kcat values of 316, 20, 74, and 36 s−1 towards 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), syringaldazine (SGZ), 2,6-dimethoxyphenol (2,6-DMP) and guaiacol, respectively. Mrl2 remained stable above pH 6 and in the presence of many metal ions, which is important for application in bioremediation. Mrl2 was investigated for the ability to degrade endocrine disrupting chemicals (EDCs) and non-steroidal anti-inflammatory drugs (NSDAIs) at neutral pH value. The enzyme accepted and converted estrone, 17β-estradiol, estriol, the synthetic contraceptive 17α-ethinyl estradiol and bisphenol A at pH 7 faster than high-potential laccases from Trametes versicolor. For example, within 30 min Mrl2 removed more than 90% bisphenol A, 17ß-estradiol, 17α-ethinyl estradiol and estriol, respectively. The concentration of the recalcitrant drug diclofenac dropped by 56% after 20 h incubation with Mrl2.Electronic supplementary materialThe online version of this article (doi:10.1186/s13568-017-0368-3) contains supplementary material, which is available to authorized users.

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“…Our previous study demonstrates that there is no significant differences in the PSR rate in XY fish treated from 0 to 30 dah by E2 alone (63%) or in combination with MT (52%), indicating that E2-induced PSR could not be rescued by simultaneous administration of exogenous androgen (Chen et al 2016). However, in the present study, the SSR induced by TR + E2, MN + E2 and GA + E2 in XY fish was successfully rescued by simultaneous administration of exogenous androgen 11-KT or MT.…”

Section: Androgens Are Essential For Male Sex Maintenance and Antagonmentioning

confidence: 90%

“…Gonads were dissected from the control XX, XY and treatment XY fish at 90 dah. Total RNA extraction, reverse transcription and real-time PCR were performed as described previously (Chen et al 2016). The relative abundances of foxl2 (forkhead box l2), cyp19a1a (cytochrome P450, family 19, subfamily A, polypeptide 1a), sf1 (steroidogenic factor 1), dmrt1 (doublesex and mab-3-related transcription factor 1), gsdf (gonadal somaderived factor), cyp11b2, cyp26a1 (cytochrome P450, family 26, subfamily A) and scp3 (synaptonemal complex protein-3) mRNA transcripts were evaluated using the formula: R = 2 −ΔΔCt , as described previously (Tao et al 2013, Sun et al 2014.…”

Section: Real-time Pcr Analysismentioning

confidence: 99%

“…The relative abundances of foxl2 (forkhead box l2), cyp19a1a (cytochrome P450, family 19, subfamily A, polypeptide 1a), sf1 (steroidogenic factor 1), dmrt1 (doublesex and mab-3-related transcription factor 1), gsdf (gonadal somaderived factor), cyp11b2, cyp26a1 (cytochrome P450, family 26, subfamily A) and scp3 (synaptonemal complex protein-3) mRNA transcripts were evaluated using the formula: R = 2 −ΔΔCt , as described previously (Tao et al 2013, Sun et al 2014. The expression values were normalized as described in our previous study (Chen et al 2016). Primer sequences used for real-time PCR are listed in Supplementary Table 1 (see section on supplementary data given at the end of this article).…”

Section: Real-time Pcr Analysismentioning

confidence: 99%

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Blockage of androgen and administration of estrogen induce transdifferentiation of testis into ovary

Shi

Gao

Liu

et al. 2017

Journal of Endocrinology

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Induction of sex reversal of XY fish has been restricted to the sex undifferentiated period. In the present study, differentiated XY tilapia were treated with trilostane (TR), metopirone (MN) and glycyrrhetinic acid (GA) (inhibitor of 3β-HSD, Cyp11b2 and 11β-HSD, respectively) alone or in combination with 17β-estradiol (E2) from 30 to 90 dah (days after hatching). At 180 dah, E2 alone resulted in 8.3%, and TR, MN and GA alone resulted in no secondary sex reversal (SSR), whereas TR + E2, MN + E2 and GA + E2 resulted in 88.3, 60.0 and 46.7% of SSR, respectively. This sex reversal could be rescued by simultaneous administration of 11-ketotestosterone (11-KT). Compared with the control XY fish, decreased serum 11-KT and increased E2 level were detected in SSR fish. Immunohistochemistry analyses revealed that Cyp19a1a, Cyp11b2 and Dmrt1 were expressed in the gonads of GA + E2, MN + E2 and TR + E2 SSR XY fish at 90 dah, but only Cyp19a1a was expressed at 180 dah. When the treatment was applied from 60 to 120 dah, TR + E2 resulted in 3.3% of SSR, MN + E2 and GA + E2 resulted in no SSR. These results demonstrated that once 11-KT was synthesized, it could antagonize E2-induced male-to-female SSR, which could be abolished by simultaneous treatment with the inhibitor of steroidogenic enzymes. The upper the enzyme was located in the steroidogenic pathway, the higher SSR rate was achieved when it was inhibited as some of the precursors, such as androstenedione, testosterone and 5α-dihydrotestosterone, could act as androgens. These results highlight the key role of androgen in male sex maintenance.

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Simultaneous exposure to estrogen and androgen resulted in feminization and endocrine disruption

Cited by 31 publications

References 65 publications

gsdf is a downstream gene of dmrt1 that functions in the male sex determination pathway of the Nile tilapia

gsdf is a downstream gene of dmrt1 that functions in the male sex determination pathway of the Nile tilapia

Expression of a new laccase from Moniliophthora roreri at high levels in Pichia pastoris and its potential application in micropollutant degradation

Blockage of androgen and administration of estrogen induce transdifferentiation of testis into ovary

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