Effects of the anti-androgen cyproterone acetate (CPA) on oocyte meiotic maturation in rainbow trout (Oncorhynchus mykiss)

• Published in: Aquatic toxicology Vol. 164; pp. 34 - 42
• Main Authors: Rime, Hélène, Nguyen, Thaovi, Ombredane, Kevin, Fostier, Alexis, Bobe, Julien
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2015; Elsevier
• Subjects: Androgen Antagonists - pharmacology; Androgen Antagonists - toxicity; Animals; Cyproterone acetate; Cyproterone Acetate - toxicity; Erk family; Female; Fish; Gene expression; Hydroxyprogesterones - metabolism; Life Sciences; Luteinizing Hormone - metabolism; Meiosis; Meiosis - drug effects; Oncorhynchus mykiss; Oncorhynchus mykiss - growth & development; Oncorhynchus mykiss - physiology; Oocyte; Oocytes - drug effects; Ovarian Follicle - drug effects; Reproduction; Reproductive Biology; Teleostei; Water Pollutants, Chemical - toxicity; Reproduction; Erk family; Fish; Meiosis; Gene expression; Cyproterone acetate; Oocyte; oocyte; meiosis; cyproteron acetate; erk family; fish; gene expression; reproduction
• ISSN: 0166-445X; 1879-1514
• DOI: 10.1016/j.aquatox.2015.04.009

•Cyproterone acetate (CPA) inhibits Lh-induced oocyte meiotic maturation in rainbow trout.•CPA inhibits the synthesis of the maturation-inducing steroid 17,20βP.•CPA inhibits Lh-induced Erk phosphorylation in the oocyte at the time of meiosis resumption.•The effects of CPA on oocyte maturation do not involve classical androgen receptors.•These results suggest a negative effect of CPA on oocyte maturation and egg production in fish.
In the present study, we aimed at characterizing the effect of cyproterone acetate (CPA), an anti-androgenic compound, on oocyte meiotic maturation in a freshwater teleost fish species, the rainbow trout (Oncorhynchus mykiss). Fully-grown post-vitellogenic ovarian follicles were incubated in vitro with CPA, luteinizing hormone (Lh) or a combination of CPA and Lh. Incubations were also performed using a combination of Lh and testosterone (T). The occurrence of oocyte maturation (i.e., resumption of the meiotic process) was assessed by monitoring germinal vesicle breakdown (GVBD) after a 72h in vitro incubation. The effect of CPA on the production of 17,20β-dihydroxy-4-pregnen-3-one (17,20βP), the natural maturation-inducing steroid (MIS), was quantified by radioimmunoassay. Our results show that CPA dramatically inhibits Lh-induced oocyte maturation and MIS synthesis. We also observed a synergistic effect of Lh and T on oocyte maturation in highly competent oocytes (i.e., able to resume meiosis after stimulation by low doses of Lh). Our results also show that a combination of CPA and Lh inhibits phosphorylation of extracellular signal-regulated kinase (Erk), kinases that are associated with oocyte maturation in many species. As a whole, our results indicate that CPA has a potential to alter meiotic maturation in rainbow trout. Further analyses are, however, needed to determine the mechanisms by which this anti-androgen interferes with the meiotic process. Furthermore, the present study provides a framework for better understanding of the ecological consequences of exposure to anti-androgens and resulting meiotic maturation abnormalities observed in trout.