Comparative reproductive toxicity of 6:2 FTS and PFOS in female zebrafish (Danio rerio): From histopathology to molecular response

Zehui Zhang; Dandan Huang; Bai Gao; Yongming Wu; Zhanxue Sun; Zhongkui Zhou; Yu Liu; Shuai Liu; Miao Zhang; Qiyu Wang

doi:10.1016/j.ecoenv.2026.120337

Comparative reproductive toxicity of 6:2 FTS and PFOS in female zebrafish (Danio rerio): From histopathology to molecular response

Ecotoxicol Environ Saf. 2026 Jun 5:322:120337. doi: 10.1016/j.ecoenv.2026.120337. Online ahead of print.

Authors

Zehui Zhang¹, Dandan Huang², Bai Gao³, Yongming Wu⁴, Zhanxue Sun², Zhongkui Zhou², Yu Liu⁴, Shuai Liu⁵, Miao Zhang⁵, Qiyu Wang⁶

Affiliations

¹ School of Water Resources & Environmental Engineering, East China University of Technology, Nanchang, Jiangxi 330013, China.
² School of Water Resources & Environmental Engineering, East China University of Technology, Nanchang, Jiangxi 330013, China; Jiangxi Provincial Key Laboratory of Groundwater Pollution Causes and Remediation, East China University of Technology, Nanchang, Jiangxi 330013, China.
³ School of Water Resources & Environmental Engineering, East China University of Technology, Nanchang, Jiangxi 330013, China; Jiangxi Provincial Key Laboratory of Groundwater Pollution Causes and Remediation, East China University of Technology, Nanchang, Jiangxi 330013, China. Electronic address: gaobai@ecut.edu.cn.
⁴ Institute of Resources and Environment, Jiangxi Academy of Sciences, Nanchang 330096, China.
⁵ Institute of Medicine and Health, Jiangxi Academy of Sciences, Nanchang 330096, China.
⁶ Institute of Medicine and Health, Jiangxi Academy of Sciences, Nanchang 330096, China. Electronic address: wangqiyu@jxas.ac.cn.

PMID: 42248039
DOI: 10.1016/j.ecoenv.2026.120337

Abstract

6:2 Fluorotelomer sulfonate (6:2 FTS), a substitute for perfluorooctane sulfonate (PFOS), is frequently detected in aquatic environments, yet its reproductive toxicity remains incompletely understood. In this study, 480 adult female zebrafish were randomly assigned to five groups: DMSO control, PFOS (0.25 and 5 μg/L), and 6:2 FTS (0.25 and 5 μg/L), with 96 fish per group and three replicate tanks. After 42 days of exposure, PFAS bioaccumulation was assessed using three fish per group; separate sets of six fish per group were used for ovarian oxidative stress, HPG-axis-related hormones, HPG-axis-related gene expression, and reproductive performance; ovarian histopathology was examined using four fish per group; offspring development was assessed using 120 embryos per group; and integrated biomarker response version 2 (IBRv2) was applied. Data are presented as mean ± SEM, with significance set at p < 0.05. Compared with PFOS, 6:2 FTS showed lower bioaccumulation in the maternal liver, ovary, brain, and offspring, but still exhibited relative accumulation in ovarian tissue. Moreover, the ovarian oxidative stress induced by 6:2 FTS was relatively mild. Both compounds disrupted HPG-axis function, increasing gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) levels while decreasing follicle-stimulating hormone (FSH), testosterone (T), and estradiol (E2) levels. Consistently, gnrh-family genes and lhβ were upregulated, whereas fshβ and 17β-hsd were downregulated. These endocrine disturbances were associated with abnormal oocyte development, increased follicular atresia, reduced spawning output, and higher offspring malformation risk. IBRv2 analysis indicated that although 6:2 FTS caused lower overall toxicity than PFOS, it still impaired reproduction mainly through HPG-axis disruption. These findings demonstrate the reproductive risk of 6:2 FTS and support careful safety evaluation of PFAS alternatives.

Keywords: 6:2 FTS; HPG axis; Oxidative stress; PFOS; Reproductive toxicity.