Molecular signaling pathways elicited by 17α-ethinylestradiol in Japanese medaka male larvae undergoing gonadal differentiation

Abdelmoneim, Ahmed; Abdu, Amira; Chen, Shuai; Sepúlveda, Marı́a S.

doi:10.1016/j.aquatox.2019.01.013

Cited by 14 publications

(6 citation statements)

References 65 publications

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“…At the conclusion of the exposure, fish were sexed based on the presence or absence of leucophores, which are known to occur along the body axis of males only (Tanaka et al, ). This method has been shown to be in concordance with the genetic screening for the dmy gene (Abdelmoneim, Abdu, Chen, & Sepulveda, ).…”

Section: Methodsmentioning

confidence: 84%

Sex‐specific endocrine‐disrupting effects of three halogenated chemicals in Japanese medaka

Godfrey

Hooser

Abdelmoneim

et al. 2019

J of Applied Toxicology

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Several halogenated chemicals are found in an array of products that can cause endocrine disruption. Human studies have shown that endocrine responses are sex specific, with females more likely to develop hypothyroidism and males more likely to have reproductive impairment. The objective of this study was to assess sex differences on thyroid and estrogenic effects after exposure of Japanese medaka (Oryzias latipes, SK2MC) to halogenated compounds. This strain is an excellent model for these studies as sex can be determined non-destructively a few hours postfertilization. Medaka embryos were exposed to sublethal concentrations of Tris(1,3-dichloro-2-propyl) phosphate (TDCPP, 0.019 mg/L), perfluorooctanoic acid (PFOA, 4.7 mg/L) and its next generation alternative, perfluorobutyric acid (PFBA, 137 mg/L). Methimazole (inhibits thyroid hormone synthesis) and the thyroid hormone triiodothyronine served as reference controls. Fish were exposed throughout embryo development until 10 days postfertilization. Females displayed significantly larger swim bladders (which are under thyroid hormone control) after exposure to all chemicals with the exception of triiodothyronine, which caused the opposite effect. Females exposed to TDCPP and PFOA had increased expression of vitellogenin and exposure to PFOA upregulated expression of multiple thyroidrelated genes. Upregulation of estrogenic-regulated genes after exposure to TDCPP, PFOA and methimazole was only observed in males. Overall, our results suggest that females and males show an estrogenic response when exposed to these halogenated chemicals and that females appear more susceptible to thyroid-induced swim bladder dysfunction compared with males. These results further confirm the importance of considering sex effects when assessing the toxicity of endocrine-disrupting compounds.

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Section: Methodsmentioning

confidence: 84%

Sex‐specific endocrine‐disrupting effects of three halogenated chemicals in Japanese medaka

Godfrey

Hooser

Abdelmoneim

et al. 2019

J of Applied Toxicology

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“…Exposure to estrogenic compounds, including the pharmaceutical estrogen 17α-ethinylestradiol (EE2), has been shown to induce intersex in certain fish species ( Abdelmoneim et al, 2019 ). There have been many studies evaluating the effects of EE2 on various fish species at different life stages, especially the model species zebrafish ( Danio rerio ), medaka, and fathead minnow.…”

Section: Introductionmentioning

confidence: 99%

Effects of early life stage exposure of largemouth bass to atrazine or a model estrogen (17α-ethinylestradiol)

Leet

Richter

Cornman

et al. 2020

PeerJ

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Endocrine disrupting contaminants are of continuing concern for potentially contributing to reproductive dysfunction in largemouth and smallmouth bass in the Chesapeake Bay watershed (CBW) and elsewhere. Exposures to atrazine (ATR) have been hypothesized to have estrogenic effects on vertebrate endocrine systems. The incidence of intersex in male smallmouth bass from some regions of CBW has been correlated with ATR concentrations in water. Fish early life stages may be particularly vulnerable to ATR exposure in agricultural areas, as a spring influx of pesticides coincides with spawning and early development. Our objectives were to investigate the effects of early life stage exposure to ATR or the model estrogen 17α-ethinylestradiol (EE2) on sexual differentiation and gene expression in gonad tissue. We exposed newly hatched largemouth bass (LMB, Micropterus salmoides) from 7 to 80 days post-spawn to nominal concentrations of 1, 10, or 100 µg ATR/L or 1 or 10 ng EE2/L and monitored histological development and transcriptomic changes in gonad tissue. We observed a nearly 100% female sex ratio in LMB exposed to EE2 at 10 ng/L, presumably due to sex reversal of males. Many gonad genes were differentially expressed between sexes. Multidimensional scaling revealed clustering by gene expression of the 1 ng EE2/L and 100 µg ATR/L-treated male fish. Some pathways responsive to EE2 exposure were not sex-specific. We observed differential expression in male gonad in LMB exposed to EE2 at 1 ng/L of several genes involved in reproductive development and function, including star, cyp11a2, ddx4 (previously vasa), wnt5b, cyp1a and samhd1. Expression of star, cyp11a2 and cyp1a in males was also responsive to ATR exposure. Overall, our results confirm that early development is a sensitive window for estrogenic endocrine disruption in LMB and are consistent with the hypothesis that ATR exposure induces some estrogenic responses in the developing gonad. However, ATR-specific and EE2-specific responses were also observed.

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“…In previous studies, exogenous hormones, such as estradiol and methyltestosterone, were observed to induce sex reversal in some aquatic animals [ 38 , 39 , 40 ]. Sex reversal represents an awesome sexual plasticity during the organism’s life cycle and triggers reproduction in animals [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Tandem Mass Tag-Based Quantitative Proteomics Analysis of Gonads Reveals New Insight into Sexual Reversal Mechanism in Chinese Soft-Shelled Turtles

Zhou

Chen

et al. 2022

Biology

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Chinese soft-shelled turtles display obvious sex dimorphism. The exogenous application of hormones (estradiol and methyltestosterone) can change the direction of gonadal differentiation of P. sinensis to produce sex reversed individuals. However, the molecular mechanism remains unclear. In this study, TMT-based quantitative proteomics analysis of four types of P. sinensis (female, male, pseudo-female, and pseudo-male) gonads were compared. Quantitative analysis of 6107 labeled proteins in the four types of P. sinensis gonads was performed. We identified 440 downregulated and 423 upregulated proteins between pseudo-females and males, as well as 394 downregulated and 959 upregulated proteins between pseudo-males and females. In the two comparisons, the differentially expressed proteins, including K7FKG1, K7GIQ2, COL4A6, K7F2U2, and K7FF80, were enriched in some important pathways, such as focal adhesion, endocytosis, apoptosis, extracellular matrix-receptor interaction, and the regulation of actin cytoskeleton, which were upregulated in pseudo-female vs. male and downregulated in pseudo-male vs. female. In pathways such as ribosome and spliceosome, the levels of RPL28, SRSF3, SNRNP40, and HNRNPK were increased from male to pseudo-female, while they decreased from female to pseudo-male. All differentially expressed proteins after sexual reversal were divided into six clusters, according to their altered levels in the four types of P. sinensis, and associated with cellular processes, such as embryonic development and catabolic process, that were closely related to sexual reversal. These data will provide clues for the sexual reversal mechanism in P. sinensis.

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Molecular signaling pathways elicited by 17α-ethinylestradiol in Japanese medaka male larvae undergoing gonadal differentiation

Cited by 14 publications

References 65 publications

Sex‐specific endocrine‐disrupting effects of three halogenated chemicals in Japanese medaka

Sex‐specific endocrine‐disrupting effects of three halogenated chemicals in Japanese medaka

Effects of early life stage exposure of largemouth bass to atrazine or a model estrogen (17α-ethinylestradiol)

Tandem Mass Tag-Based Quantitative Proteomics Analysis of Gonads Reveals New Insight into Sexual Reversal Mechanism in Chinese Soft-Shelled Turtles

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