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Updated: Aug 22, 2025
Dissection of Larval Zebrafish Gonadal Tissue
Published on: April 26, 2017
Rxrs and their partner receptor genes inducing masculinization plausibly mediated by endocrine disruption in
Congcong Zou1, Lijuan Wang2, Chang Shu1
1CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Abstract:
Retinoid X receptors (RXRs) can form homo- or heterodimers with orphan receptors involved in multiple intertwined signaling pathways. However, there is limited study on the formation of sex phenotypes and the regulation of steroidogenesis by RXRs in fish. Here, in Paralichthys olivaceus, we first indicated that PPARγ::RXRα was predictably a transcription factor for steroidogenesis genes, and Foxl2 and Dmrt1 were also transcription factors for rxrs and their partner receptor genes. When the flounder fry were exposed to LG100268 (LG, RXRs agonist, 50 mg/kg diet), the percentage of males increased from 50% to 71.4%. Before histological differentiation of the flounder ovary (3 cm TL) and testis (6 cm TL), the transcripts of rar β and rar γ (P < 0.05) were activated, and the steroidogenesis gene Hsd3b1 was down-regulated (P < 0.05). The ratios of testosterone (T)/17β-estradiol (E2) were all greatly increased (P < 0.05), and the ratio of 11-ketotestosterone (11-KT)/E2 was elevated at 3 cm TL. Moreover, LG was used to treat the cultured gonads in vitro (10 μM) and the fish with intraperitoneal injection in vivo (12 mg/kg body weight), respectively. LG was able to up-regulate rxr γ, rar γ, and ppar δ, and Hsd3b1 was significantly up-regulated (P < 0.05). The ratios of 11-KT/E2 in the culture medium and in the ovaries of the fish were decreased. Furthermore, the recombinant flounder Foxl2 protein was able to significantly down-regulate ppar γ (P < 0.05) and tr β (P < 0.01) in the ovaries in vitro, and the result of the Dmrt1 in the testes was opposite to that of the Foxl2, probably indicating a feedback loop between RXRs' partner receptors and Foxl2/Dmrt1. These findings introduce for the first time the mode of action of RXRs on the flounder steroidogenesis and provide important data to learn the potential function of RXRs in fish sex differentiation and the potential role of RXRs in aquatic animals in the presence of water pollutants.
Insights
Retinoid X receptors (RXRs) influence fish sex determination and steroid hormone production. RXR activation by LG100268 increased male percentages and altered sex hormone ratios in flounder, revealing RXRs
Area of Science:
- Endocrinology
- Aquatic toxicology
- Molecular biology
Background:
- Retinoid X receptors (RXRs) are crucial nuclear receptors involved in diverse signaling pathways.
- Limited research exists on RXR roles in fish sex phenotype development and steroidogenesis regulation.
- Understanding RXR function is vital for assessing environmental impacts on aquatic reproduction.
Purpose of the Study:
- To investigate the role of RXRs in sex determination and steroidogenesis in the fish Paralichthys olivaceus.
- To elucidate the regulatory mechanisms of RXRs and their partner receptors in fish gonadal development.
- To assess the impact of RXR agonists on sex differentiation and steroidogenic gene expression.
Main Methods:
- Exposure of flounder fry to LG100268, an RXR agonist, to assess effects on sex ratio.
- Quantitative analysis of steroidogenic and receptor gene expression during gonadal differentiation.
- In vitro and in vivo experiments using cultured gonads and fish to evaluate LG100268 effects.
- Investigating interactions between RXR partner receptors (Foxl2, Dmrt1) and their regulatory targets.
Main Results:
- LG100268 treatment significantly increased the male percentage in flounder fry.
- RXR and related gene expression patterns were identified during ovarian and testicular differentiation.
- LG100268 modulated steroidogenic gene expression (Hsd3b1) and sex hormone ratios (T/E2, 11-KT/E2).
- Foxl2 and Dmrt1 exhibited opposing regulatory effects on RXR partner receptors, suggesting a feedback loop.
Conclusions:
- RXRs play a significant role in regulating steroidogenesis and sex differentiation in fish.
- LG100268, an RXR agonist, can promote male development and alter steroid hormone profiles.
- A potential feedback mechanism exists between RXR partner receptors and transcription factors Foxl2/Dmrt1.
- Findings provide insights into RXR functions in fish reproduction and potential risks from water pollutants.
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