2. Academic Validation
  3. Rxrs and their partner receptor genes inducing masculinization plausibly mediated by endocrine disruption in Paralichthys olivaceus

Rxrs and their partner receptor genes inducing masculinization plausibly mediated by endocrine disruption in Paralichthys olivaceus

  • J Steroid Biochem Mol Biol. 2022 Nov 8;226:106219. doi: 10.1016/j.jsbmb.2022.106219.
Congcong Zou 1,  Lijuan Wang 2,  Chang Shu 1,  Xungang Tan 2,  Zhihao Wu 2,  Yuxia Zou 2,  Ze Li 1,  Guoyu Wang 2,  Zongcheng Song 3,  Feng You 4
Affiliations

Affiliations

  • 1 CAS 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.
  • 2 CAS 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.
  • 3 Shenghang Aquatic Science and Technology Co. Ltd., Weihai 264200, PR China.
  • 4 CAS 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. Electronic address: youfeng@qdio.ac.cn.
PMID: 36356854 DOI: 10.1016/j.jsbmb.2022.106219
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.

Keywords

Flounder; Gonad; LG100268; Retinoid X receptors; Sex differentiation; Steroidogenesis.

Figures
Products