Maternal exposure to zearalenone in masculinization window affects the fetal Leydig cell development in rat male fetus. (August 2020)

• Record Type: Journal Article
• Authors: Pan, Peipei; Ma, Feifei; Wu, Keyang; Yu, Yige; Li, Yang; Li, Zengqiang; Chen, Xiuxiu; Huang, Tongliang; Wang, Yiyan; Ge, Ren-shan
• Is Part Of: Environmental pollution. Volume 263(2020)Supplement Part B
• Publication Date: 2020-08
• Subjects: Fetal leydig cell -- Anogenital distance -- Stem leydig cell -- Notch signaling -- Zearalenone; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2020.114357
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Zearalenone is a phenolic Fusarium mycotoxin, which is ubiquitous in human and animal feedstuff and often co-occurs with other mycotoxins. ZEA has been reported to disturb Leydig cell function and even cause the apoptosis to the Leydig cells. However, the effects of gestational exposure to zearalenone on fetal Leydig cells and the underlying mechanism remain unknown. Sprague Dawley dams were daily gavaged with 0, 2.5, 5, 10, and 20 mg/kg body weight ZEA from gestational day 14–21. On gestational day 21, rats were euthanized and serum testosterone levels were measured, and testes were collected for further evaluation of Leydig cell number, cell size, gene, and protein expression. Zearalenone significantly decreased anogenital distance and its index of male fetus, serum testosterone levels, Leydig cell proteins (SCARB1, STAR, CYP11A1, CYP17A1, and INSL3), and fetal Leydig cell number at 10 and/or 20 mg/kg by delaying the commitment of stem Leydig cells into the Leydig cell lineage and proliferation. Further study found that Notch signaling (RFNG, PSEN1, NOTCH1, and NOTCH3) was up-regulated by zearalenone. In conclusion, gestational exposure to high doses of zearalenone (10 and 20 mg/kg) blocks fetal Leydig cell development, thus possibly causing the anomalies of the male reproductive tract. Graphical abstract: Image 1 Highlights: Gestational exposure to zearalenone lowers fetal Leydig cell number. Gestational exposure to zearalenone inhibits testosterone synthesis in male fetuses. Gestational exposure to zearalenone to activate Notch signaling to maintain stem Leydig cell as undifferentiated fate.