Testosterone Mediates Reproductive Toxicity in Caenorhabditis elegans by Affecting Sex Determination in Germ Cells through nhr-69/mpk-1/fog-1/3

• Published in: Toxics (Basel) Vol. 12; no. 7; p. 502
• Main Authors: Meng, Ke, Shi, Ying-Chi, Li, Wei-Xi, Wang, Jia, Cheng, Bei-Jing, Li, Tian-Lin, Li, Hui, Jiang, Nan, Liu, Ran
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.07.2024
• Subjects: Aquatic ecosystems; Aquatic environment; benchmark dose (BMD); Caenorhabditis elegans; Cell size; Ecological risk assessment; Endocrine disruptors; Endocrine system; Fog; Gene expression; Genes; Germ cells; Hormones; Medical research; Medicine, Experimental; Nematodes; nhr-69; Offspring; Proteins; Risk assessment; Sex; Sex determination; Sex determination, Diagnostic; Sperm; Steroids; Testosterone; testosterone (T); Toxicity; Wildlife; China; United States > US; Japan; Caenorhabditis elegans; testosterone (T); benchmark dose (BMD); nhr-69; sex determination
• ISSN: 2305-6304; 2305-6304
• DOI: 10.3390/toxics12070502

Testosterone (T), an environmental androgen, significantly disrupts endocrine systems in wildlife and ecosystems. Despite growing concern over its high levels in aquatic environments, the reproductive toxicity of testosterone and its mechanisms are not well understood. In this study, we investigated the reproductive toxicity and mechanisms of testosterone using Caenorhabditis elegans (C. elegans) and assessed its ecological toxicity through the benchmark dose (BMD) method. Our results indicate that T concentrations exceeding 0.01 μg/L significantly reduce the brood size, decrease germ cell counts, and prolong the generation time in C. elegans as T concentrations increase. Furthermore, to elucidate the specific mechanisms, we analyzed the expression of nhr-69, mpk-1, and other genes involved in sex determination. These findings suggest that the nhr-69-mediated reproductive toxicity of T primarily affects sperm formation and the offspring number by influencing its downstream targets, mpk-1 and fog-1/3, which are critical in the germ cell sex-determining pathway. Additionally, this study determined that the 10% lower boundary of the baseline dose (BMDL10) is 1.160 ng/L, offering a more protective reference dose for the ecological risk assessment of T. The present study suggests that nhr-69 mediates the reproductive toxicity of T by influencing mpk-1 and fog-1/3, critical genes at the end of the germ cell sex-determining pathway, thereby providing a basis for establishing reproductive toxicity thresholds for T.