monocrotophos and Feminization

Monocrotophos (MCP) is an organophosphorus pesticide moderately toxic to fish, and it has significant estrogenic properties in vivo. In this study, zebrafish (Danio rerio) were exposed to 0.001, 0.010, and 0.100 mg/L 40% MCP pesticide in a semi-static manner from fertilization to 40 days post-hatching. Histological analyses were performed to determine whether sex differentiation in zebrafish was affected by MCP, and the mRNA expression levels of genes involved in sexual differentiation were quantified by real-time PCR to clarify the possible mechanism(s) of action. The results revealed a prominent increase in the proportion of females (71%) in the 0.100 mg/L MCP pesticide treatment as well as the presence of one intersex individual in each of the groups exposed to 0.001 and 0.100 mg/L MCP. MCP exposure stimulated forkhead transcription factor gene L2 (foxl2) expression and suppressed doublesex/mab-3 related transcription factor 1 (dmrt1) expression, indirectly leading to elevated gonadal aromatase (cyp19a1a) gene expression, which should promote phenotypic feminization. In addition, MCP treatment increased the transcription of brain aromatase (cyp19a1b), resulting in an indirect impact on sexual differentiation. The results from this investigation can be used for risk and hazard assessment of MCP pesticide.

Topics: Animals; Aromatase; Dose-Response Relationship, Drug; Female; Feminization; Forkhead Box Protein L2; Forkhead Transcription Factors; Gene Expression Regulation, Developmental; Insecticides; Isoenzymes; Male; Monocrotophos; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sex Differentiation; Time Factors; Toxicity Tests; Transcription Factors; Zebrafish; Zebrafish Proteins

Monocrotophos is a highly toxic organophosphorus pesticide that has been confirmed to be an endocrine-disrupting chemical. To evaluate the influence of this pollutant on the reproductive system of male fish, we studied the sex steroid levels, reproductive traits, sex ratio, and reproductive success in male guppies (Poecilia reticulata) exposed to 40% monocrotophos pesticide at the nominal concentrations of 0.01, 0.10, and 1.00 mg/L for 90 days from birth to adulthood in a semi-static exposure system. Radioimmunoassay and western blot analyses demonstrated that the long-term exposure to monocrotophos pesticide during the sexual development of male guppies caused a significant increase in 17β-estradiol levels and consequently induced vitellogenin synthesis, suggesting the feminization of the males. Monocrotophos pesticide also caused a significant decrease in testosterone levels, which consequently inhibited testis growth and reduced the sperm count and the area and intensity of their sexually attractive orange spots, which collectively indicated the significant demasculinization of the male sexual characteristics. Furthermore, these changes in the sexual characteristics at the cellular and organ levels translated into ecologically important effects on the reproductive success at the individual level, as measured by a decrease in offspring production and survival rate. The present study provides the first evidence that monocrotophos pesticide can cause severe reproductive abnormalities in fish due to its endocrine-disrupting action.

Topics: Animals; Blotting, Western; Dose-Response Relationship, Drug; Endocrine Disruptors; Estradiol; Feminization; Gonadal Steroid Hormones; Male; Monocrotophos; Pesticides; Poecilia; Radioimmunoassay; Reproduction; Sex Characteristics; Sexual Development; Sperm Count; Survival Rate; Testis; Testosterone; Vitellogenins